Prostate Volume as a Risk Factor for Lower Urinary Tract Symptoms: The Quest Continues

It is well known that lower urinary tract symptoms (LUTS) may regress, progress, or remain stable. Several parameters including age, maximum urinary flow rate, postvoid residual urine volume, serum prostate-specific antigen (PSA), and prostate volume (PV) were associated with the risk of progression in men with moderate to severe LUTS in clinical trial populations and community studies [1], [2], and [3]. EAU guidelines on non-neurogenic male LUTS recognize the important role of an enlarged prostate in LUTS management among men with bothersome symptoms by including prostate size as a decision point in the treatment algorithm [4].

However, there is a paucity of data on the role of PV as a predictor of LUTS progression in men with mild to no symptoms. Data from the Krimpen study showed that PV could be a risk factor for incident LUTS according to univariate analysis; however, after multivariate analysis this effect disappeared [5]. However, increased PSA (a proxy measure for PV) remained a risk factor for LUTS after multivariate analysis.

A 4-yr longitudinal study tried to identify predictors for clinical progression (defined as migration to moderate or severe symptoms) among men with mild LUTS using an artificial neural network that could determine the relative importance of the input variables [6]. The variables of importance for disease progression were, in order of statistical significance, PSA level, obstructive symptom score, and transitional zone volume. Interestingly, the predictive value of total PV did not reach statistical significance.

In this issue of European Urology, Simon et al [7] present a very interesting post hoc analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study that supports the notion that men with mild to no LUTS (International Prostate Symptom Score <8) but increased prostate size are at higher risk of incident LUTS presumed due to benign prostatic hyperplasia (BPH) [7]. More specifically, among men treated with placebo during the 4-yr REDUCE study, those with a prostate size of 40.1–80 ml had a 67% higher risk (hazard risk 1.67, 95% confidence interval 1.23–2.26; p = 0.001) of developing incident LUTS compared to men with smaller prostates. It was also found that there was no association between prostate size and the risk of incident LUTS in men treated with 0.5 mg of dutasteride.

As with prior studies on LUTS, two concerns arise as to the translation of these data into clinical practice:

• 1. Are these results applicable to the general population? One limitation of this post hoc analysis of the REDUCE study is its select population, consisting of men taking a placebo with high PSA (median 5.5 ng/ml), prostate volume <80 ml (median 40.3 ml), and one prior negative biopsy. Therefore, these findings should be interpreted with caution before extrapolation to individual patients.
• 2. What is the significance of these data from a clinical point of view? Can we offer medical treatment to prevent or delay bothersome LUTS onset or other adverse events among men with no or mild symptoms? A post hoc analysis of the Prostate Cancer Prevention Trial (PCPT) focused on the preventative role of finasteride in the management of mild LUTS in men [8]. On the basis of 7 yr of treatment, the number needed to treat (NNT) to prevent one clinical BPH case ranged from 58 for men aged 55–59 yr age to 31 for men older than 65 yr, but NNT was not adjusted for prostate size. In the current study by Simon et al, the reduction in the absolute risk of incident LUTS in men with a prostate volume of 40.1–80 ml treated with dutasteride was 11.7%, resulting in NNT of nine [7]. Of note, the PCPT population had lower PSA and smaller prostates than in the REDUCE trial due to differences in study design. The potential side effects of 5a-reductase inhibitors must also be taken into account, including loss of libido, erectile dysfunction, and gynecomastia. In addition, it is well known that LUTS have a multifactorial etiology, so prostate may not be the only contributor to incident LUTS.

Currently, medical prophylaxis for LUTS cannot be justified. LUTS impose a significant economic burden on health care systems that is set to increase in line with greater life expectancy. In the era of health care reform and global economic pressure, a cost-effective strategy targeting lifestyle factors and intervening in LUTS well before treatment is indicated would be welcome. Implementation of risk stratification for LUTS prevention represents a major challenge. Future research should focus on prevention and improved strategies for subgroups of patients most likely to develop incident LUTS and at high risk of acute urinary retention and surgery. The present study provides evidence that PV plays a role in the development of incident LUTS in men, and furthers our understanding of the natural history of LUTS. However, more risk factors need to be identified to accurately define specific patient groups. The quest for identification of such risk factors continues.

It is well known that lower urinary tract symptoms (LUTS) may regress, progress, or remain stable. Several parameters including age, maximum urinary flow rate, postvoid residual urine volume, serum prostate-specific antigen (PSA), and prostate volume (PV) were associated with the risk of progression in men with moderate to severe LUTS in clinical trial populations and community studies [1], [2], and [3]. EAU guidelines on non-neurogenic male LUTS recognize the important role of an enlarged prostate in LUTS management among men with bothersome symptoms by including prostate size as a decision point in the treatment algorithm [4].

However, there is a paucity of data on the role of PV as a predictor of LUTS progression in men with mild to no symptoms. Data from the Krimpen study showed that PV could be a risk factor for incident LUTS according to univariate analysis; however, after multivariate analysis this effect disappeared [5]. However, increased PSA (a proxy measure for PV) remained a risk factor for LUTS after multivariate analysis.

A 4-yr longitudinal study tried to identify predictors for clinical progression (defined as migration to moderate or severe symptoms) among men with mild LUTS using an artificial neural network that could determine the relative importance of the input variables [6]. The variables of importance for disease progression were, in order of statistical significance, PSA level, obstructive symptom score, and transitional zone volume. Interestingly, the predictive value of total PV did not reach statistical significance.

In this issue of European Urology, Simon et al [7] present a very interesting post hoc analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study that supports the notion that men with mild to no LUTS (International Prostate Symptom Score <8) but increased prostate size are at higher risk of incident LUTS presumed due to benign prostatic hyperplasia (BPH) [7]. More specifically, among men treated with placebo during the 4-yr REDUCE study, those with a prostate size of 40.1–80 ml had a 67% higher risk (hazard risk 1.67, 95% confidence interval 1.23–2.26; p = 0.001) of developing incident LUTS compared to men with smaller prostates. It was also found that there was no association between prostate size and the risk of incident LUTS in men treated with 0.5 mg of dutasteride.

As with prior studies on LUTS, two concerns arise as to the translation of these data into clinical practice:

• 1. Are these results applicable to the general population? One limitation of this post hoc analysis of the REDUCE study is its select population, consisting of men taking a placebo with high PSA (median 5.5 ng/ml), prostate volume <80 ml (median 40.3 ml), and one prior negative biopsy. Therefore, these findings should be interpreted with caution before extrapolation to individual patients.
• 2. What is the significance of these data from a clinical point of view? Can we offer medical treatment to prevent or delay bothersome LUTS onset or other adverse events among men with no or mild symptoms? A post hoc analysis of the Prostate Cancer Prevention Trial (PCPT) focused on the preventative role of finasteride in the management of mild LUTS in men [8]. On the basis of 7 yr of treatment, the number needed to treat (NNT) to prevent one clinical BPH case ranged from 58 for men aged 55–59 yr age to 31 for men older than 65 yr, but NNT was not adjusted for prostate size. In the current study by Simon et al, the reduction in the absolute risk of incident LUTS in men with a prostate volume of 40.1–80 ml treated with dutasteride was 11.7%, resulting in NNT of nine [7]. Of note, the PCPT population had lower PSA and smaller prostates than in the REDUCE trial due to differences in study design. The potential side effects of 5a-reductase inhibitors must also be taken into account, including loss of libido, erectile dysfunction, and gynecomastia. In addition, it is well known that LUTS have a multifactorial etiology, so prostate may not be the only contributor to incident LUTS.

Currently, medical prophylaxis for LUTS cannot be justified. LUTS impose a significant economic burden on health care systems that is set to increase in line with greater life expectancy. In the era of health care reform and global economic pressure, a cost-effective strategy targeting lifestyle factors and intervening in LUTS well before treatment is indicated would be welcome. Implementation of risk stratification for LUTS prevention represents a major challenge. Future research should focus on prevention and improved strategies for subgroups of patients most likely to develop incident LUTS and at high risk of acute urinary retention and surgery. The present study provides evidence that PV plays a role in the development of incident LUTS in men, and furthers our understanding of the natural history of LUTS. However, more risk factors need to be identified to accurately define specific patient groups. The quest for identification of such risk factors continues.

It is well known that lower urinary tract symptoms (LUTS) may regress, progress, or remain stable. Several parameters including age, maximum urinary flow rate, postvoid residual urine volume, serum prostate-specific antigen (PSA), and prostate volume (PV) were associated with the risk of progression in men with moderate to severe LUTS in clinical trial populations and community studies [1], [2], and [3]. EAU guidelines on non-neurogenic male LUTS recognize the important role of an enlarged prostate in LUTS management among men with bothersome symptoms by including prostate size as a decision point in the treatment algorithm [4].

However, there is a paucity of data on the role of PV as a predictor of LUTS progression in men with mild to no symptoms. Data from the Krimpen study showed that PV could be a risk factor for incident LUTS according to univariate analysis; however, after multivariate analysis this effect disappeared [5]. However, increased PSA (a proxy measure for PV) remained a risk factor for LUTS after multivariate analysis.

A 4-yr longitudinal study tried to identify predictors for clinical progression (defined as migration to moderate or severe symptoms) among men with mild LUTS using an artificial neural network that could determine the relative importance of the input variables [6]. The variables of importance for disease progression were, in order of statistical significance, PSA level, obstructive symptom score, and transitional zone volume. Interestingly, the predictive value of total PV did not reach statistical significance.

In this issue of European Urology, Simon et al [7] present a very interesting post hoc analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study that supports the notion that men with mild to no LUTS (International Prostate Symptom Score <8) but increased prostate size are at higher risk of incident LUTS presumed due to benign prostatic hyperplasia (BPH) [7]. More specifically, among men treated with placebo during the 4-yr REDUCE study, those with a prostate size of 40.1–80 ml had a 67% higher risk (hazard risk 1.67, 95% confidence interval 1.23–2.26; p = 0.001) of developing incident LUTS compared to men with smaller prostates. It was also found that there was no association between prostate size and the risk of incident LUTS in men treated with 0.5 mg of dutasteride.

As with prior studies on LUTS, two concerns arise as to the translation of these data into clinical practice:

• 1. Are these results applicable to the general population? One limitation of this post hoc analysis of the REDUCE study is its select population, consisting of men taking a placebo with high PSA (median 5.5 ng/ml), prostate volume <80 ml (median 40.3 ml), and one prior negative biopsy. Therefore, these findings should be interpreted with caution before extrapolation to individual patients.
• 2. What is the significance of these data from a clinical point of view? Can we offer medical treatment to prevent or delay bothersome LUTS onset or other adverse events among men with no or mild symptoms? A post hoc analysis of the Prostate Cancer Prevention Trial (PCPT) focused on the preventative role of finasteride in the management of mild LUTS in men [8]. On the basis of 7 yr of treatment, the number needed to treat (NNT) to prevent one clinical BPH case ranged from 58 for men aged 55–59 yr age to 31 for men older than 65 yr, but NNT was not adjusted for prostate size. In the current study by Simon et al, the reduction in the absolute risk of incident LUTS in men with a prostate volume of 40.1–80 ml treated with dutasteride was 11.7%, resulting in NNT of nine [7]. Of note, the PCPT population had lower PSA and smaller prostates than in the REDUCE trial due to differences in study design. The potential side effects of 5a-reductase inhibitors must also be taken into account, including loss of libido, erectile dysfunction, and gynecomastia. In addition, it is well known that LUTS have a multifactorial etiology, so prostate may not be the only contributor to incident LUTS.

Currently, medical prophylaxis for LUTS cannot be justified. LUTS impose a significant economic burden on health care systems that is set to increase in line with greater life expectancy. In the era of health care reform and global economic pressure, a cost-effective strategy targeting lifestyle factors and intervening in LUTS well before treatment is indicated would be welcome. Implementation of risk stratification for LUTS prevention represents a major challenge. Future research should focus on prevention and improved strategies for subgroups of patients most likely to develop incident LUTS and at high risk of acute urinary retention and surgery. The present study provides evidence that PV plays a role in the development of incident LUTS in men, and furthers our understanding of the natural history of LUTS. However, more risk factors need to be identified to accurately define specific patient groups. The quest for identification of such risk factors continues.

It is well known that lower urinary tract symptoms (LUTS) may regress, progress, or remain stable. Several parameters including age, maximum urinary flow rate, postvoid residual urine volume, serum prostate-specific antigen (PSA), and prostate volume (PV) were associated with the risk of progression in men with moderate to severe LUTS in clinical trial populations and community studies [1], [2], and [3]. EAU guidelines on non-neurogenic male LUTS recognize the important role of an enlarged prostate in LUTS management among men with bothersome symptoms by including prostate size as a decision point in the treatment algorithm [4].

However, there is a paucity of data on the role of PV as a predictor of LUTS progression in men with mild to no symptoms. Data from the Krimpen study showed that PV could be a risk factor for incident LUTS according to univariate analysis; however, after multivariate analysis this effect disappeared [5]. However, increased PSA (a proxy measure for PV) remained a risk factor for LUTS after multivariate analysis.

A 4-yr longitudinal study tried to identify predictors for clinical progression (defined as migration to moderate or severe symptoms) among men with mild LUTS using an artificial neural network that could determine the relative importance of the input variables [6]. The variables of importance for disease progression were, in order of statistical significance, PSA level, obstructive symptom score, and transitional zone volume. Interestingly, the predictive value of total PV did not reach statistical significance.

In this issue of European Urology, Simon et al [7] present a very interesting post hoc analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study that supports the notion that men with mild to no LUTS (International Prostate Symptom Score <8) but increased prostate size are at higher risk of incident LUTS presumed due to benign prostatic hyperplasia (BPH) [7]. More specifically, among men treated with placebo during the 4-yr REDUCE study, those with a prostate size of 40.1–80 ml had a 67% higher risk (hazard risk 1.67, 95% confidence interval 1.23–2.26; p = 0.001) of developing incident LUTS compared to men with smaller prostates. It was also found that there was no association between prostate size and the risk of incident LUTS in men treated with 0.5 mg of dutasteride.

As with prior studies on LUTS, two concerns arise as to the translation of these data into clinical practice:

• 1. Are these results applicable to the general population? One limitation of this post hoc analysis of the REDUCE study is its select population, consisting of men taking a placebo with high PSA (median 5.5 ng/ml), prostate volume <80 ml (median 40.3 ml), and one prior negative biopsy. Therefore, these findings should be interpreted with caution before extrapolation to individual patients.
• 2. What is the significance of these data from a clinical point of view? Can we offer medical treatment to prevent or delay bothersome LUTS onset or other adverse events among men with no or mild symptoms? A post hoc analysis of the Prostate Cancer Prevention Trial (PCPT) focused on the preventative role of finasteride in the management of mild LUTS in men [8]. On the basis of 7 yr of treatment, the number needed to treat (NNT) to prevent one clinical BPH case ranged from 58 for men aged 55–59 yr age to 31 for men older than 65 yr, but NNT was not adjusted for prostate size. In the current study by Simon et al, the reduction in the absolute risk of incident LUTS in men with a prostate volume of 40.1–80 ml treated with dutasteride was 11.7%, resulting in NNT of nine [7]. Of note, the PCPT population had lower PSA and smaller prostates than in the REDUCE trial due to differences in study design. The potential side effects of 5a-reductase inhibitors must also be taken into account, including loss of libido, erectile dysfunction, and gynecomastia. In addition, it is well known that LUTS have a multifactorial etiology, so prostate may not be the only contributor to incident LUTS.

Currently, medical prophylaxis for LUTS cannot be justified. LUTS impose a significant economic burden on health care systems that is set to increase in line with greater life expectancy. In the era of health care reform and global economic pressure, a cost-effective strategy targeting lifestyle factors and intervening in LUTS well before treatment is indicated would be welcome. Implementation of risk stratification for LUTS prevention represents a major challenge. Future research should focus on prevention and improved strategies for subgroups of patients most likely to develop incident LUTS and at high risk of acute urinary retention and surgery. The present study provides evidence that PV plays a role in the development of incident LUTS in men, and furthers our understanding of the natural history of LUTS. However, more risk factors need to be identified to accurately define specific patient groups. The quest for identification of such risk factors continues.

It is well known that lower urinary tract symptoms (LUTS) may regress, progress, or remain stable. Several parameters including age, maximum urinary flow rate, postvoid residual urine volume, serum prostate-specific antigen (PSA), and prostate volume (PV) were associated with the risk of progression in men with moderate to severe LUTS in clinical trial populations and community studies [1], [2], and [3]. EAU guidelines on non-neurogenic male LUTS recognize the important role of an enlarged prostate in LUTS management among men with bothersome symptoms by including prostate size as a decision point in the treatment algorithm [4].

However, there is a paucity of data on the role of PV as a predictor of LUTS progression in men with mild to no symptoms. Data from the Krimpen study showed that PV could be a risk factor for incident LUTS according to univariate analysis; however, after multivariate analysis this effect disappeared [5]. However, increased PSA (a proxy measure for PV) remained a risk factor for LUTS after multivariate analysis.

A 4-yr longitudinal study tried to identify predictors for clinical progression (defined as migration to moderate or severe symptoms) among men with mild LUTS using an artificial neural network that could determine the relative importance of the input variables [6]. The variables of importance for disease progression were, in order of statistical significance, PSA level, obstructive symptom score, and transitional zone volume. Interestingly, the predictive value of total PV did not reach statistical significance.

In this issue of European Urology, Simon et al [7] present a very interesting post hoc analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study that supports the notion that men with mild to no LUTS (International Prostate Symptom Score <8) but increased prostate size are at higher risk of incident LUTS presumed due to benign prostatic hyperplasia (BPH) [7]. More specifically, among men treated with placebo during the 4-yr REDUCE study, those with a prostate size of 40.1–80 ml had a 67% higher risk (hazard risk 1.67, 95% confidence interval 1.23–2.26; p = 0.001) of developing incident LUTS compared to men with smaller prostates. It was also found that there was no association between prostate size and the risk of incident LUTS in men treated with 0.5 mg of dutasteride.

As with prior studies on LUTS, two concerns arise as to the translation of these data into clinical practice:

• 1. Are these results applicable to the general population? One limitation of this post hoc analysis of the REDUCE study is its select population, consisting of men taking a placebo with high PSA (median 5.5 ng/ml), prostate volume <80 ml (median 40.3 ml), and one prior negative biopsy. Therefore, these findings should be interpreted with caution before extrapolation to individual patients.
• 2. What is the significance of these data from a clinical point of view? Can we offer medical treatment to prevent or delay bothersome LUTS onset or other adverse events among men with no or mild symptoms? A post hoc analysis of the Prostate Cancer Prevention Trial (PCPT) focused on the preventative role of finasteride in the management of mild LUTS in men [8]. On the basis of 7 yr of treatment, the number needed to treat (NNT) to prevent one clinical BPH case ranged from 58 for men aged 55–59 yr age to 31 for men older than 65 yr, but NNT was not adjusted for prostate size. In the current study by Simon et al, the reduction in the absolute risk of incident LUTS in men with a prostate volume of 40.1–80 ml treated with dutasteride was 11.7%, resulting in NNT of nine [7]. Of note, the PCPT population had lower PSA and smaller prostates than in the REDUCE trial due to differences in study design. The potential side effects of 5a-reductase inhibitors must also be taken into account, including loss of libido, erectile dysfunction, and gynecomastia. In addition, it is well known that LUTS have a multifactorial etiology, so prostate may not be the only contributor to incident LUTS.

Currently, medical prophylaxis for LUTS cannot be justified. LUTS impose a significant economic burden on health care systems that is set to increase in line with greater life expectancy. In the era of health care reform and global economic pressure, a cost-effective strategy targeting lifestyle factors and intervening in LUTS well before treatment is indicated would be welcome. Implementation of risk stratification for LUTS prevention represents a major challenge. Future research should focus on prevention and improved strategies for subgroups of patients most likely to develop incident LUTS and at high risk of acute urinary retention and surgery. The present study provides evidence that PV plays a role in the development of incident LUTS in men, and furthers our understanding of the natural history of LUTS. However, more risk factors need to be identified to accurately define specific patient groups. The quest for identification of such risk factors continues.

It is well known that lower urinary tract symptoms (LUTS) may regress, progress, or remain stable. Several parameters including age, maximum urinary flow rate, postvoid residual urine volume, serum prostate-specific antigen (PSA), and prostate volume (PV) were associated with the risk of progression in men with moderate to severe LUTS in clinical trial populations and community studies [1], [2], and [3]. EAU guidelines on non-neurogenic male LUTS recognize the important role of an enlarged prostate in LUTS management among men with bothersome symptoms by including prostate size as a decision point in the treatment algorithm [4].

However, there is a paucity of data on the role of PV as a predictor of LUTS progression in men with mild to no symptoms. Data from the Krimpen study showed that PV could be a risk factor for incident LUTS according to univariate analysis; however, after multivariate analysis this effect disappeared [5]. However, increased PSA (a proxy measure for PV) remained a risk factor for LUTS after multivariate analysis.

A 4-yr longitudinal study tried to identify predictors for clinical progression (defined as migration to moderate or severe symptoms) among men with mild LUTS using an artificial neural network that could determine the relative importance of the input variables [6]. The variables of importance for disease progression were, in order of statistical significance, PSA level, obstructive symptom score, and transitional zone volume. Interestingly, the predictive value of total PV did not reach statistical significance.

In this issue of European Urology, Simon et al [7] present a very interesting post hoc analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study that supports the notion that men with mild to no LUTS (International Prostate Symptom Score <8) but increased prostate size are at higher risk of incident LUTS presumed due to benign prostatic hyperplasia (BPH) [7]. More specifically, among men treated with placebo during the 4-yr REDUCE study, those with a prostate size of 40.1–80 ml had a 67% higher risk (hazard risk 1.67, 95% confidence interval 1.23–2.26; p = 0.001) of developing incident LUTS compared to men with smaller prostates. It was also found that there was no association between prostate size and the risk of incident LUTS in men treated with 0.5 mg of dutasteride.

As with prior studies on LUTS, two concerns arise as to the translation of these data into clinical practice:

• 1. Are these results applicable to the general population? One limitation of this post hoc analysis of the REDUCE study is its select population, consisting of men taking a placebo with high PSA (median 5.5 ng/ml), prostate volume <80 ml (median 40.3 ml), and one prior negative biopsy. Therefore, these findings should be interpreted with caution before extrapolation to individual patients.
• 2. What is the significance of these data from a clinical point of view? Can we offer medical treatment to prevent or delay bothersome LUTS onset or other adverse events among men with no or mild symptoms? A post hoc analysis of the Prostate Cancer Prevention Trial (PCPT) focused on the preventative role of finasteride in the management of mild LUTS in men [8]. On the basis of 7 yr of treatment, the number needed to treat (NNT) to prevent one clinical BPH case ranged from 58 for men aged 55–59 yr age to 31 for men older than 65 yr, but NNT was not adjusted for prostate size. In the current study by Simon et al, the reduction in the absolute risk of incident LUTS in men with a prostate volume of 40.1–80 ml treated with dutasteride was 11.7%, resulting in NNT of nine [7]. Of note, the PCPT population had lower PSA and smaller prostates than in the REDUCE trial due to differences in study design. The potential side effects of 5a-reductase inhibitors must also be taken into account, including loss of libido, erectile dysfunction, and gynecomastia. In addition, it is well known that LUTS have a multifactorial etiology, so prostate may not be the only contributor to incident LUTS.

Currently, medical prophylaxis for LUTS cannot be justified. LUTS impose a significant economic burden on health care systems that is set to increase in line with greater life expectancy. In the era of health care reform and global economic pressure, a cost-effective strategy targeting lifestyle factors and intervening in LUTS well before treatment is indicated would be welcome. Implementation of risk stratification for LUTS prevention represents a major challenge. Future research should focus on prevention and improved strategies for subgroups of patients most likely to develop incident LUTS and at high risk of acute urinary retention and surgery. The present study provides evidence that PV plays a role in the development of incident LUTS in men, and furthers our understanding of the natural history of LUTS. However, more risk factors need to be identified to accurately define specific patient groups. The quest for identification of such risk factors continues.

It is well known that lower urinary tract symptoms (LUTS) may regress, progress, or remain stable. Several parameters including age, maximum urinary flow rate, postvoid residual urine volume, serum prostate-specific antigen (PSA), and prostate volume (PV) were associated with the risk of progression in men with moderate to severe LUTS in clinical trial populations and community studies [1], [2], and [3]. EAU guidelines on non-neurogenic male LUTS recognize the important role of an enlarged prostate in LUTS management among men with bothersome symptoms by including prostate size as a decision point in the treatment algorithm [4].

However, there is a paucity of data on the role of PV as a predictor of LUTS progression in men with mild to no symptoms. Data from the Krimpen study showed that PV could be a risk factor for incident LUTS according to univariate analysis; however, after multivariate analysis this effect disappeared [5]. However, increased PSA (a proxy measure for PV) remained a risk factor for LUTS after multivariate analysis.

A 4-yr longitudinal study tried to identify predictors for clinical progression (defined as migration to moderate or severe symptoms) among men with mild LUTS using an artificial neural network that could determine the relative importance of the input variables [6]. The variables of importance for disease progression were, in order of statistical significance, PSA level, obstructive symptom score, and transitional zone volume. Interestingly, the predictive value of total PV did not reach statistical significance.

In this issue of European Urology, Simon et al [7] present a very interesting post hoc analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study that supports the notion that men with mild to no LUTS (International Prostate Symptom Score <8) but increased prostate size are at higher risk of incident LUTS presumed due to benign prostatic hyperplasia (BPH) [7]. More specifically, among men treated with placebo during the 4-yr REDUCE study, those with a prostate size of 40.1–80 ml had a 67% higher risk (hazard risk 1.67, 95% confidence interval 1.23–2.26; p = 0.001) of developing incident LUTS compared to men with smaller prostates. It was also found that there was no association between prostate size and the risk of incident LUTS in men treated with 0.5 mg of dutasteride.

As with prior studies on LUTS, two concerns arise as to the translation of these data into clinical practice:

• 1. Are these results applicable to the general population? One limitation of this post hoc analysis of the REDUCE study is its select population, consisting of men taking a placebo with high PSA (median 5.5 ng/ml), prostate volume <80 ml (median 40.3 ml), and one prior negative biopsy. Therefore, these findings should be interpreted with caution before extrapolation to individual patients.
• 2. What is the significance of these data from a clinical point of view? Can we offer medical treatment to prevent or delay bothersome LUTS onset or other adverse events among men with no or mild symptoms? A post hoc analysis of the Prostate Cancer Prevention Trial (PCPT) focused on the preventative role of finasteride in the management of mild LUTS in men [8]. On the basis of 7 yr of treatment, the number needed to treat (NNT) to prevent one clinical BPH case ranged from 58 for men aged 55–59 yr age to 31 for men older than 65 yr, but NNT was not adjusted for prostate size. In the current study by Simon et al, the reduction in the absolute risk of incident LUTS in men with a prostate volume of 40.1–80 ml treated with dutasteride was 11.7%, resulting in NNT of nine [7]. Of note, the PCPT population had lower PSA and smaller prostates than in the REDUCE trial due to differences in study design. The potential side effects of 5a-reductase inhibitors must also be taken into account, including loss of libido, erectile dysfunction, and gynecomastia. In addition, it is well known that LUTS have a multifactorial etiology, so prostate may not be the only contributor to incident LUTS.

Currently, medical prophylaxis for LUTS cannot be justified. LUTS impose a significant economic burden on health care systems that is set to increase in line with greater life expectancy. In the era of health care reform and global economic pressure, a cost-effective strategy targeting lifestyle factors and intervening in LUTS well before treatment is indicated would be welcome. Implementation of risk stratification for LUTS prevention represents a major challenge. Future research should focus on prevention and improved strategies for subgroups of patients most likely to develop incident LUTS and at high risk of acute urinary retention and surgery. The present study provides evidence that PV plays a role in the development of incident LUTS in men, and furthers our understanding of the natural history of LUTS. However, more risk factors need to be identified to accurately define specific patient groups. The quest for identification of such risk factors continues.

It is well known that lower urinary tract symptoms (LUTS) may regress, progress, or remain stable. Several parameters including age, maximum urinary flow rate, postvoid residual urine volume, serum prostate-specific antigen (PSA), and prostate volume (PV) were associated with the risk of progression in men with moderate to severe LUTS in clinical trial populations and community studies [1], [2], and [3]. EAU guidelines on non-neurogenic male LUTS recognize the important role of an enlarged prostate in LUTS management among men with bothersome symptoms by including prostate size as a decision point in the treatment algorithm [4].

However, there is a paucity of data on the role of PV as a predictor of LUTS progression in men with mild to no symptoms. Data from the Krimpen study showed that PV could be a risk factor for incident LUTS according to univariate analysis; however, after multivariate analysis this effect disappeared [5]. However, increased PSA (a proxy measure for PV) remained a risk factor for LUTS after multivariate analysis.

A 4-yr longitudinal study tried to identify predictors for clinical progression (defined as migration to moderate or severe symptoms) among men with mild LUTS using an artificial neural network that could determine the relative importance of the input variables [6]. The variables of importance for disease progression were, in order of statistical significance, PSA level, obstructive symptom score, and transitional zone volume. Interestingly, the predictive value of total PV did not reach statistical significance.

In this issue of European Urology, Simon et al [7] present a very interesting post hoc analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study that supports the notion that men with mild to no LUTS (International Prostate Symptom Score <8) but increased prostate size are at higher risk of incident LUTS presumed due to benign prostatic hyperplasia (BPH) [7]. More specifically, among men treated with placebo during the 4-yr REDUCE study, those with a prostate size of 40.1–80 ml had a 67% higher risk (hazard risk 1.67, 95% confidence interval 1.23–2.26; p = 0.001) of developing incident LUTS compared to men with smaller prostates. It was also found that there was no association between prostate size and the risk of incident LUTS in men treated with 0.5 mg of dutasteride.

As with prior studies on LUTS, two concerns arise as to the translation of these data into clinical practice:

• 1. Are these results applicable to the general population? One limitation of this post hoc analysis of the REDUCE study is its select population, consisting of men taking a placebo with high PSA (median 5.5 ng/ml), prostate volume <80 ml (median 40.3 ml), and one prior negative biopsy. Therefore, these findings should be interpreted with caution before extrapolation to individual patients.
• 2. What is the significance of these data from a clinical point of view? Can we offer medical treatment to prevent or delay bothersome LUTS onset or other adverse events among men with no or mild symptoms? A post hoc analysis of the Prostate Cancer Prevention Trial (PCPT) focused on the preventative role of finasteride in the management of mild LUTS in men [8]. On the basis of 7 yr of treatment, the number needed to treat (NNT) to prevent one clinical BPH case ranged from 58 for men aged 55–59 yr age to 31 for men older than 65 yr, but NNT was not adjusted for prostate size. In the current study by Simon et al, the reduction in the absolute risk of incident LUTS in men with a prostate volume of 40.1–80 ml treated with dutasteride was 11.7%, resulting in NNT of nine [7]. Of note, the PCPT population had lower PSA and smaller prostates than in the REDUCE trial due to differences in study design. The potential side effects of 5a-reductase inhibitors must also be taken into account, including loss of libido, erectile dysfunction, and gynecomastia. In addition, it is well known that LUTS have a multifactorial etiology, so prostate may not be the only contributor to incident LUTS.

Currently, medical prophylaxis for LUTS cannot be justified. LUTS impose a significant economic burden on health care systems that is set to increase in line with greater life expectancy. In the era of health care reform and global economic pressure, a cost-effective strategy targeting lifestyle factors and intervening in LUTS well before treatment is indicated would be welcome. Implementation of risk stratification for LUTS prevention represents a major challenge. Future research should focus on prevention and improved strategies for subgroups of patients most likely to develop incident LUTS and at high risk of acute urinary retention and surgery. The present study provides evidence that PV plays a role in the development of incident LUTS in men, and furthers our understanding of the natural history of LUTS. However, more risk factors need to be identified to accurately define specific patient groups. The quest for identification of such risk factors continues.

It is well known that lower urinary tract symptoms (LUTS) may regress, progress, or remain stable. Several parameters including age, maximum urinary flow rate, postvoid residual urine volume, serum prostate-specific antigen (PSA), and prostate volume (PV) were associated with the risk of progression in men with moderate to severe LUTS in clinical trial populations and community studies [1], [2], and [3]. EAU guidelines on non-neurogenic male LUTS recognize the important role of an enlarged prostate in LUTS management among men with bothersome symptoms by including prostate size as a decision point in the treatment algorithm [4].

However, there is a paucity of data on the role of PV as a predictor of LUTS progression in men with mild to no symptoms. Data from the Krimpen study showed that PV could be a risk factor for incident LUTS according to univariate analysis; however, after multivariate analysis this effect disappeared [5]. However, increased PSA (a proxy measure for PV) remained a risk factor for LUTS after multivariate analysis.

A 4-yr longitudinal study tried to identify predictors for clinical progression (defined as migration to moderate or severe symptoms) among men with mild LUTS using an artificial neural network that could determine the relative importance of the input variables [6]. The variables of importance for disease progression were, in order of statistical significance, PSA level, obstructive symptom score, and transitional zone volume. Interestingly, the predictive value of total PV did not reach statistical significance.

In this issue of European Urology, Simon et al [7] present a very interesting post hoc analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study that supports the notion that men with mild to no LUTS (International Prostate Symptom Score <8) but increased prostate size are at higher risk of incident LUTS presumed due to benign prostatic hyperplasia (BPH) [7]. More specifically, among men treated with placebo during the 4-yr REDUCE study, those with a prostate size of 40.1–80 ml had a 67% higher risk (hazard risk 1.67, 95% confidence interval 1.23–2.26; p = 0.001) of developing incident LUTS compared to men with smaller prostates. It was also found that there was no association between prostate size and the risk of incident LUTS in men treated with 0.5 mg of dutasteride.

As with prior studies on LUTS, two concerns arise as to the translation of these data into clinical practice:

• 1. Are these results applicable to the general population? One limitation of this post hoc analysis of the REDUCE study is its select population, consisting of men taking a placebo with high PSA (median 5.5 ng/ml), prostate volume <80 ml (median 40.3 ml), and one prior negative biopsy. Therefore, these findings should be interpreted with caution before extrapolation to individual patients.
• 2. What is the significance of these data from a clinical point of view? Can we offer medical treatment to prevent or delay bothersome LUTS onset or other adverse events among men with no or mild symptoms? A post hoc analysis of the Prostate Cancer Prevention Trial (PCPT) focused on the preventative role of finasteride in the management of mild LUTS in men [8]. On the basis of 7 yr of treatment, the number needed to treat (NNT) to prevent one clinical BPH case ranged from 58 for men aged 55–59 yr age to 31 for men older than 65 yr, but NNT was not adjusted for prostate size. In the current study by Simon et al, the reduction in the absolute risk of incident LUTS in men with a prostate volume of 40.1–80 ml treated with dutasteride was 11.7%, resulting in NNT of nine [7]. Of note, the PCPT population had lower PSA and smaller prostates than in the REDUCE trial due to differences in study design. The potential side effects of 5a-reductase inhibitors must also be taken into account, including loss of libido, erectile dysfunction, and gynecomastia. In addition, it is well known that LUTS have a multifactorial etiology, so prostate may not be the only contributor to incident LUTS.

Currently, medical prophylaxis for LUTS cannot be justified. LUTS impose a significant economic burden on health care systems that is set to increase in line with greater life expectancy. In the era of health care reform and global economic pressure, a cost-effective strategy targeting lifestyle factors and intervening in LUTS well before treatment is indicated would be welcome. Implementation of risk stratification for LUTS prevention represents a major challenge. Future research should focus on prevention and improved strategies for subgroups of patients most likely to develop incident LUTS and at high risk of acute urinary retention and surgery. The present study provides evidence that PV plays a role in the development of incident LUTS in men, and furthers our understanding of the natural history of LUTS. However, more risk factors need to be identified to accurately define specific patient groups. The quest for identification of such risk factors continues.

It is well known that lower urinary tract symptoms (LUTS) may regress, progress, or remain stable. Several parameters including age, maximum urinary flow rate, postvoid residual urine volume, serum prostate-specific antigen (PSA), and prostate volume (PV) were associated with the risk of progression in men with moderate to severe LUTS in clinical trial populations and community studies [1], [2], and [3]. EAU guidelines on non-neurogenic male LUTS recognize the important role of an enlarged prostate in LUTS management among men with bothersome symptoms by including prostate size as a decision point in the treatment algorithm [4].

However, there is a paucity of data on the role of PV as a predictor of LUTS progression in men with mild to no symptoms. Data from the Krimpen study showed that PV could be a risk factor for incident LUTS according to univariate analysis; however, after multivariate analysis this effect disappeared [5]. However, increased PSA (a proxy measure for PV) remained a risk factor for LUTS after multivariate analysis.

A 4-yr longitudinal study tried to identify predictors for clinical progression (defined as migration to moderate or severe symptoms) among men with mild LUTS using an artificial neural network that could determine the relative importance of the input variables [6]. The variables of importance for disease progression were, in order of statistical significance, PSA level, obstructive symptom score, and transitional zone volume. Interestingly, the predictive value of total PV did not reach statistical significance.

In this issue of European Urology, Simon et al [7] present a very interesting post hoc analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study that supports the notion that men with mild to no LUTS (International Prostate Symptom Score <8) but increased prostate size are at higher risk of incident LUTS presumed due to benign prostatic hyperplasia (BPH) [7]. More specifically, among men treated with placebo during the 4-yr REDUCE study, those with a prostate size of 40.1–80 ml had a 67% higher risk (hazard risk 1.67, 95% confidence interval 1.23–2.26; p = 0.001) of developing incident LUTS compared to men with smaller prostates. It was also found that there was no association between prostate size and the risk of incident LUTS in men treated with 0.5 mg of dutasteride.

As with prior studies on LUTS, two concerns arise as to the translation of these data into clinical practice:

• 1. Are these results applicable to the general population? One limitation of this post hoc analysis of the REDUCE study is its select population, consisting of men taking a placebo with high PSA (median 5.5 ng/ml), prostate volume <80 ml (median 40.3 ml), and one prior negative biopsy. Therefore, these findings should be interpreted with caution before extrapolation to individual patients.
• 2. What is the significance of these data from a clinical point of view? Can we offer medical treatment to prevent or delay bothersome LUTS onset or other adverse events among men with no or mild symptoms? A post hoc analysis of the Prostate Cancer Prevention Trial (PCPT) focused on the preventative role of finasteride in the management of mild LUTS in men [8]. On the basis of 7 yr of treatment, the number needed to treat (NNT) to prevent one clinical BPH case ranged from 58 for men aged 55–59 yr age to 31 for men older than 65 yr, but NNT was not adjusted for prostate size. In the current study by Simon et al, the reduction in the absolute risk of incident LUTS in men with a prostate volume of 40.1–80 ml treated with dutasteride was 11.7%, resulting in NNT of nine [7]. Of note, the PCPT population had lower PSA and smaller prostates than in the REDUCE trial due to differences in study design. The potential side effects of 5a-reductase inhibitors must also be taken into account, including loss of libido, erectile dysfunction, and gynecomastia. In addition, it is well known that LUTS have a multifactorial etiology, so prostate may not be the only contributor to incident LUTS.

Currently, medical prophylaxis for LUTS cannot be justified. LUTS impose a significant economic burden on health care systems that is set to increase in line with greater life expectancy. In the era of health care reform and global economic pressure, a cost-effective strategy targeting lifestyle factors and intervening in LUTS well before treatment is indicated would be welcome. Implementation of risk stratification for LUTS prevention represents a major challenge. Future research should focus on prevention and improved strategies for subgroups of patients most likely to develop incident LUTS and at high risk of acute urinary retention and surgery. The present study provides evidence that PV plays a role in the development of incident LUTS in men, and furthers our understanding of the natural history of LUTS. However, more risk factors need to be identified to accurately define specific patient groups. The quest for identification of such risk factors continues.

It is well known that lower urinary tract symptoms (LUTS) may regress, progress, or remain stable. Several parameters including age, maximum urinary flow rate, postvoid residual urine volume, serum prostate-specific antigen (PSA), and prostate volume (PV) were associated with the risk of progression in men with moderate to severe LUTS in clinical trial populations and community studies [1], [2], and [3]. EAU guidelines on non-neurogenic male LUTS recognize the important role of an enlarged prostate in LUTS management among men with bothersome symptoms by including prostate size as a decision point in the treatment algorithm [4].

However, there is a paucity of data on the role of PV as a predictor of LUTS progression in men with mild to no symptoms. Data from the Krimpen study showed that PV could be a risk factor for incident LUTS according to univariate analysis; however, after multivariate analysis this effect disappeared [5]. However, increased PSA (a proxy measure for PV) remained a risk factor for LUTS after multivariate analysis.

A 4-yr longitudinal study tried to identify predictors for clinical progression (defined as migration to moderate or severe symptoms) among men with mild LUTS using an artificial neural network that could determine the relative importance of the input variables [6]. The variables of importance for disease progression were, in order of statistical significance, PSA level, obstructive symptom score, and transitional zone volume. Interestingly, the predictive value of total PV did not reach statistical significance.

In this issue of European Urology, Simon et al [7] present a very interesting post hoc analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study that supports the notion that men with mild to no LUTS (International Prostate Symptom Score <8) but increased prostate size are at higher risk of incident LUTS presumed due to benign prostatic hyperplasia (BPH) [7]. More specifically, among men treated with placebo during the 4-yr REDUCE study, those with a prostate size of 40.1–80 ml had a 67% higher risk (hazard risk 1.67, 95% confidence interval 1.23–2.26; p = 0.001) of developing incident LUTS compared to men with smaller prostates. It was also found that there was no association between prostate size and the risk of incident LUTS in men treated with 0.5 mg of dutasteride.

As with prior studies on LUTS, two concerns arise as to the translation of these data into clinical practice:

• 1. Are these results applicable to the general population? One limitation of this post hoc analysis of the REDUCE study is its select population, consisting of men taking a placebo with high PSA (median 5.5 ng/ml), prostate volume <80 ml (median 40.3 ml), and one prior negative biopsy. Therefore, these findings should be interpreted with caution before extrapolation to individual patients.
• 2. What is the significance of these data from a clinical point of view? Can we offer medical treatment to prevent or delay bothersome LUTS onset or other adverse events among men with no or mild symptoms? A post hoc analysis of the Prostate Cancer Prevention Trial (PCPT) focused on the preventative role of finasteride in the management of mild LUTS in men [8]. On the basis of 7 yr of treatment, the number needed to treat (NNT) to prevent one clinical BPH case ranged from 58 for men aged 55–59 yr age to 31 for men older than 65 yr, but NNT was not adjusted for prostate size. In the current study by Simon et al, the reduction in the absolute risk of incident LUTS in men with a prostate volume of 40.1–80 ml treated with dutasteride was 11.7%, resulting in NNT of nine [7]. Of note, the PCPT population had lower PSA and smaller prostates than in the REDUCE trial due to differences in study design. The potential side effects of 5a-reductase inhibitors must also be taken into account, including loss of libido, erectile dysfunction, and gynecomastia. In addition, it is well known that LUTS have a multifactorial etiology, so prostate may not be the only contributor to incident LUTS.

Currently, medical prophylaxis for LUTS cannot be justified. LUTS impose a significant economic burden on health care systems that is set to increase in line with greater life expectancy. In the era of health care reform and global economic pressure, a cost-effective strategy targeting lifestyle factors and intervening in LUTS well before treatment is indicated would be welcome. Implementation of risk stratification for LUTS prevention represents a major challenge. Future research should focus on prevention and improved strategies for subgroups of patients most likely to develop incident LUTS and at high risk of acute urinary retention and surgery. The present study provides evidence that PV plays a role in the development of incident LUTS in men, and furthers our understanding of the natural history of LUTS. However, more risk factors need to be identified to accurately define specific patient groups. The quest for identification of such risk factors continues.

It is well known that lower urinary tract symptoms (LUTS) may regress, progress, or remain stable. Several parameters including age, maximum urinary flow rate, postvoid residual urine volume, serum prostate-specific antigen (PSA), and prostate volume (PV) were associated with the risk of progression in men with moderate to severe LUTS in clinical trial populations and community studies [1], [2], and [3]. EAU guidelines on non-neurogenic male LUTS recognize the important role of an enlarged prostate in LUTS management among men with bothersome symptoms by including prostate size as a decision point in the treatment algorithm [4].

However, there is a paucity of data on the role of PV as a predictor of LUTS progression in men with mild to no symptoms. Data from the Krimpen study showed that PV could be a risk factor for incident LUTS according to univariate analysis; however, after multivariate analysis this effect disappeared [5]. However, increased PSA (a proxy measure for PV) remained a risk factor for LUTS after multivariate analysis.

A 4-yr longitudinal study tried to identify predictors for clinical progression (defined as migration to moderate or severe symptoms) among men with mild LUTS using an artificial neural network that could determine the relative importance of the input variables [6]. The variables of importance for disease progression were, in order of statistical significance, PSA level, obstructive symptom score, and transitional zone volume. Interestingly, the predictive value of total PV did not reach statistical significance.

In this issue of European Urology, Simon et al [7] present a very interesting post hoc analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study that supports the notion that men with mild to no LUTS (International Prostate Symptom Score <8) but increased prostate size are at higher risk of incident LUTS presumed due to benign prostatic hyperplasia (BPH) [7]. More specifically, among men treated with placebo during the 4-yr REDUCE study, those with a prostate size of 40.1–80 ml had a 67% higher risk (hazard risk 1.67, 95% confidence interval 1.23–2.26; p = 0.001) of developing incident LUTS compared to men with smaller prostates. It was also found that there was no association between prostate size and the risk of incident LUTS in men treated with 0.5 mg of dutasteride.

As with prior studies on LUTS, two concerns arise as to the translation of these data into clinical practice:

• 1. Are these results applicable to the general population? One limitation of this post hoc analysis of the REDUCE study is its select population, consisting of men taking a placebo with high PSA (median 5.5 ng/ml), prostate volume <80 ml (median 40.3 ml), and one prior negative biopsy. Therefore, these findings should be interpreted with caution before extrapolation to individual patients.
• 2. What is the significance of these data from a clinical point of view? Can we offer medical treatment to prevent or delay bothersome LUTS onset or other adverse events among men with no or mild symptoms? A post hoc analysis of the Prostate Cancer Prevention Trial (PCPT) focused on the preventative role of finasteride in the management of mild LUTS in men [8]. On the basis of 7 yr of treatment, the number needed to treat (NNT) to prevent one clinical BPH case ranged from 58 for men aged 55–59 yr age to 31 for men older than 65 yr, but NNT was not adjusted for prostate size. In the current study by Simon et al, the reduction in the absolute risk of incident LUTS in men with a prostate volume of 40.1–80 ml treated with dutasteride was 11.7%, resulting in NNT of nine [7]. Of note, the PCPT population had lower PSA and smaller prostates than in the REDUCE trial due to differences in study design. The potential side effects of 5a-reductase inhibitors must also be taken into account, including loss of libido, erectile dysfunction, and gynecomastia. In addition, it is well known that LUTS have a multifactorial etiology, so prostate may not be the only contributor to incident LUTS.

Currently, medical prophylaxis for LUTS cannot be justified. LUTS impose a significant economic burden on health care systems that is set to increase in line with greater life expectancy. In the era of health care reform and global economic pressure, a cost-effective strategy targeting lifestyle factors and intervening in LUTS well before treatment is indicated would be welcome. Implementation of risk stratification for LUTS prevention represents a major challenge. Future research should focus on prevention and improved strategies for subgroups of patients most likely to develop incident LUTS and at high risk of acute urinary retention and surgery. The present study provides evidence that PV plays a role in the development of incident LUTS in men, and furthers our understanding of the natural history of LUTS. However, more risk factors need to be identified to accurately define specific patient groups. The quest for identification of such risk factors continues.

It is well known that lower urinary tract symptoms (LUTS) may regress, progress, or remain stable. Several parameters including age, maximum urinary flow rate, postvoid residual urine volume, serum prostate-specific antigen (PSA), and prostate volume (PV) were associated with the risk of progression in men with moderate to severe LUTS in clinical trial populations and community studies [1], [2], and [3]. EAU guidelines on non-neurogenic male LUTS recognize the important role of an enlarged prostate in LUTS management among men with bothersome symptoms by including prostate size as a decision point in the treatment algorithm [4].

However, there is a paucity of data on the role of PV as a predictor of LUTS progression in men with mild to no symptoms. Data from the Krimpen study showed that PV could be a risk factor for incident LUTS according to univariate analysis; however, after multivariate analysis this effect disappeared [5]. However, increased PSA (a proxy measure for PV) remained a risk factor for LUTS after multivariate analysis.

A 4-yr longitudinal study tried to identify predictors for clinical progression (defined as migration to moderate or severe symptoms) among men with mild LUTS using an artificial neural network that could determine the relative importance of the input variables [6]. The variables of importance for disease progression were, in order of statistical significance, PSA level, obstructive symptom score, and transitional zone volume. Interestingly, the predictive value of total PV did not reach statistical significance.

In this issue of European Urology, Simon et al [7] present a very interesting post hoc analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study that supports the notion that men with mild to no LUTS (International Prostate Symptom Score <8) but increased prostate size are at higher risk of incident LUTS presumed due to benign prostatic hyperplasia (BPH) [7]. More specifically, among men treated with placebo during the 4-yr REDUCE study, those with a prostate size of 40.1–80 ml had a 67% higher risk (hazard risk 1.67, 95% confidence interval 1.23–2.26; p = 0.001) of developing incident LUTS compared to men with smaller prostates. It was also found that there was no association between prostate size and the risk of incident LUTS in men treated with 0.5 mg of dutasteride.

As with prior studies on LUTS, two concerns arise as to the translation of these data into clinical practice:

• 1. Are these results applicable to the general population? One limitation of this post hoc analysis of the REDUCE study is its select population, consisting of men taking a placebo with high PSA (median 5.5 ng/ml), prostate volume <80 ml (median 40.3 ml), and one prior negative biopsy. Therefore, these findings should be interpreted with caution before extrapolation to individual patients.
• 2. What is the significance of these data from a clinical point of view? Can we offer medical treatment to prevent or delay bothersome LUTS onset or other adverse events among men with no or mild symptoms? A post hoc analysis of the Prostate Cancer Prevention Trial (PCPT) focused on the preventative role of finasteride in the management of mild LUTS in men [8]. On the basis of 7 yr of treatment, the number needed to treat (NNT) to prevent one clinical BPH case ranged from 58 for men aged 55–59 yr age to 31 for men older than 65 yr, but NNT was not adjusted for prostate size. In the current study by Simon et al, the reduction in the absolute risk of incident LUTS in men with a prostate volume of 40.1–80 ml treated with dutasteride was 11.7%, resulting in NNT of nine [7]. Of note, the PCPT population had lower PSA and smaller prostates than in the REDUCE trial due to differences in study design. The potential side effects of 5a-reductase inhibitors must also be taken into account, including loss of libido, erectile dysfunction, and gynecomastia. In addition, it is well known that LUTS have a multifactorial etiology, so prostate may not be the only contributor to incident LUTS.

Currently, medical prophylaxis for LUTS cannot be justified. LUTS impose a significant economic burden on health care systems that is set to increase in line with greater life expectancy. In the era of health care reform and global economic pressure, a cost-effective strategy targeting lifestyle factors and intervening in LUTS well before treatment is indicated would be welcome. Implementation of risk stratification for LUTS prevention represents a major challenge. Future research should focus on prevention and improved strategies for subgroups of patients most likely to develop incident LUTS and at high risk of acute urinary retention and surgery. The present study provides evidence that PV plays a role in the development of incident LUTS in men, and furthers our understanding of the natural history of LUTS. However, more risk factors need to be identified to accurately define specific patient groups. The quest for identification of such risk factors continues.

It is well known that lower urinary tract symptoms (LUTS) may regress, progress, or remain stable. Several parameters including age, maximum urinary flow rate, postvoid residual urine volume, serum prostate-specific antigen (PSA), and prostate volume (PV) were associated with the risk of progression in men with moderate to severe LUTS in clinical trial populations and community studies [1], [2], and [3]. EAU guidelines on non-neurogenic male LUTS recognize the important role of an enlarged prostate in LUTS management among men with bothersome symptoms by including prostate size as a decision point in the treatment algorithm [4].

However, there is a paucity of data on the role of PV as a predictor of LUTS progression in men with mild to no symptoms. Data from the Krimpen study showed that PV could be a risk factor for incident LUTS according to univariate analysis; however, after multivariate analysis this effect disappeared [5]. However, increased PSA (a proxy measure for PV) remained a risk factor for LUTS after multivariate analysis.

A 4-yr longitudinal study tried to identify predictors for clinical progression (defined as migration to moderate or severe symptoms) among men with mild LUTS using an artificial neural network that could determine the relative importance of the input variables [6]. The variables of importance for disease progression were, in order of statistical significance, PSA level, obstructive symptom score, and transitional zone volume. Interestingly, the predictive value of total PV did not reach statistical significance.

In this issue of European Urology, Simon et al [7] present a very interesting post hoc analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study that supports the notion that men with mild to no LUTS (International Prostate Symptom Score <8) but increased prostate size are at higher risk of incident LUTS presumed due to benign prostatic hyperplasia (BPH) [7]. More specifically, among men treated with placebo during the 4-yr REDUCE study, those with a prostate size of 40.1–80 ml had a 67% higher risk (hazard risk 1.67, 95% confidence interval 1.23–2.26; p = 0.001) of developing incident LUTS compared to men with smaller prostates. It was also found that there was no association between prostate size and the risk of incident LUTS in men treated with 0.5 mg of dutasteride.

As with prior studies on LUTS, two concerns arise as to the translation of these data into clinical practice:

• 1. Are these results applicable to the general population? One limitation of this post hoc analysis of the REDUCE study is its select population, consisting of men taking a placebo with high PSA (median 5.5 ng/ml), prostate volume <80 ml (median 40.3 ml), and one prior negative biopsy. Therefore, these findings should be interpreted with caution before extrapolation to individual patients.
• 2. What is the significance of these data from a clinical point of view? Can we offer medical treatment to prevent or delay bothersome LUTS onset or other adverse events among men with no or mild symptoms? A post hoc analysis of the Prostate Cancer Prevention Trial (PCPT) focused on the preventative role of finasteride in the management of mild LUTS in men [8]. On the basis of 7 yr of treatment, the number needed to treat (NNT) to prevent one clinical BPH case ranged from 58 for men aged 55–59 yr age to 31 for men older than 65 yr, but NNT was not adjusted for prostate size. In the current study by Simon et al, the reduction in the absolute risk of incident LUTS in men with a prostate volume of 40.1–80 ml treated with dutasteride was 11.7%, resulting in NNT of nine [7]. Of note, the PCPT population had lower PSA and smaller prostates than in the REDUCE trial due to differences in study design. The potential side effects of 5a-reductase inhibitors must also be taken into account, including loss of libido, erectile dysfunction, and gynecomastia. In addition, it is well known that LUTS have a multifactorial etiology, so prostate may not be the only contributor to incident LUTS.

Currently, medical prophylaxis for LUTS cannot be justified. LUTS impose a significant economic burden on health care systems that is set to increase in line with greater life expectancy. In the era of health care reform and global economic pressure, a cost-effective strategy targeting lifestyle factors and intervening in LUTS well before treatment is indicated would be welcome. Implementation of risk stratification for LUTS prevention represents a major challenge. Future research should focus on prevention and improved strategies for subgroups of patients most likely to develop incident LUTS and at high risk of acute urinary retention and surgery. The present study provides evidence that PV plays a role in the development of incident LUTS in men, and furthers our understanding of the natural history of LUTS. However, more risk factors need to be identified to accurately define specific patient groups. The quest for identification of such risk factors continues.

It is well known that lower urinary tract symptoms (LUTS) may regress, progress, or remain stable. Several parameters including age, maximum urinary flow rate, postvoid residual urine volume, serum prostate-specific antigen (PSA), and prostate volume (PV) were associated with the risk of progression in men with moderate to severe LUTS in clinical trial populations and community studies [1], [2], and [3]. EAU guidelines on non-neurogenic male LUTS recognize the important role of an enlarged prostate in LUTS management among men with bothersome symptoms by including prostate size as a decision point in the treatment algorithm [4].

However, there is a paucity of data on the role of PV as a predictor of LUTS progression in men with mild to no symptoms. Data from the Krimpen study showed that PV could be a risk factor for incident LUTS according to univariate analysis; however, after multivariate analysis this effect disappeared [5]. However, increased PSA (a proxy measure for PV) remained a risk factor for LUTS after multivariate analysis.

A 4-yr longitudinal study tried to identify predictors for clinical progression (defined as migration to moderate or severe symptoms) among men with mild LUTS using an artificial neural network that could determine the relative importance of the input variables [6]. The variables of importance for disease progression were, in order of statistical significance, PSA level, obstructive symptom score, and transitional zone volume. Interestingly, the predictive value of total PV did not reach statistical significance.

In this issue of European Urology, Simon et al [7] present a very interesting post hoc analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study that supports the notion that men with mild to no LUTS (International Prostate Symptom Score <8) but increased prostate size are at higher risk of incident LUTS presumed due to benign prostatic hyperplasia (BPH) [7]. More specifically, among men treated with placebo during the 4-yr REDUCE study, those with a prostate size of 40.1–80 ml had a 67% higher risk (hazard risk 1.67, 95% confidence interval 1.23–2.26; p = 0.001) of developing incident LUTS compared to men with smaller prostates. It was also found that there was no association between prostate size and the risk of incident LUTS in men treated with 0.5 mg of dutasteride.

As with prior studies on LUTS, two concerns arise as to the translation of these data into clinical practice:

• 1. Are these results applicable to the general population? One limitation of this post hoc analysis of the REDUCE study is its select population, consisting of men taking a placebo with high PSA (median 5.5 ng/ml), prostate volume <80 ml (median 40.3 ml), and one prior negative biopsy. Therefore, these findings should be interpreted with caution before extrapolation to individual patients.
• 2. What is the significance of these data from a clinical point of view? Can we offer medical treatment to prevent or delay bothersome LUTS onset or other adverse events among men with no or mild symptoms? A post hoc analysis of the Prostate Cancer Prevention Trial (PCPT) focused on the preventative role of finasteride in the management of mild LUTS in men [8]. On the basis of 7 yr of treatment, the number needed to treat (NNT) to prevent one clinical BPH case ranged from 58 for men aged 55–59 yr age to 31 for men older than 65 yr, but NNT was not adjusted for prostate size. In the current study by Simon et al, the reduction in the absolute risk of incident LUTS in men with a prostate volume of 40.1–80 ml treated with dutasteride was 11.7%, resulting in NNT of nine [7]. Of note, the PCPT population had lower PSA and smaller prostates than in the REDUCE trial due to differences in study design. The potential side effects of 5a-reductase inhibitors must also be taken into account, including loss of libido, erectile dysfunction, and gynecomastia. In addition, it is well known that LUTS have a multifactorial etiology, so prostate may not be the only contributor to incident LUTS.

Currently, medical prophylaxis for LUTS cannot be justified. LUTS impose a significant economic burden on health care systems that is set to increase in line with greater life expectancy. In the era of health care reform and global economic pressure, a cost-effective strategy targeting lifestyle factors and intervening in LUTS well before treatment is indicated would be welcome. Implementation of risk stratification for LUTS prevention represents a major challenge. Future research should focus on prevention and improved strategies for subgroups of patients most likely to develop incident LUTS and at high risk of acute urinary retention and surgery. The present study provides evidence that PV plays a role in the development of incident LUTS in men, and furthers our understanding of the natural history of LUTS. However, more risk factors need to be identified to accurately define specific patient groups. The quest for identification of such risk factors continues.