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Re: Prediction of Erectile Function Following Treatment for Prostate Cancer
Urological Survey
Urological Oncology: Prostate Cancer Re: Prediction of Erectile Function Following Treatment for Prostate Cancer M. Alemozaffar, M. M. Regan, M. R. Cooperberg, J. T. Wei, J. M. Michalski, H. M. Sandler, L. Hembroff, N. Sadetsky, C. S. Saigal, M. S. Litwin, E. Klein, A. S. Kibel, D. A. Hamstra, L. L. Pisters, D. A. Kuban, I. D. Kaplan, D. P. Wood, J. Ciezki, R. L. Dunn, P. R. Carroll and M. G. Sanda Urology Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts JAMA 2011; 306: 1205–1214.
Context: Sexual function is the health-related quality of life (HRQOL) domain most commonly impaired after prostate cancer treatment; however, validated tools to enable personalized prediction of erectile dysfunction after prostate cancer treatment are lacking. Objective: To predict long-term erectile function following prostate cancer treatment based on individual patient and treatment characteristics. Design: Pretreatment patient characteristics, sexual HRQOL, and treatment details measured in a longitudinal academic multicenter cohort (Prostate Cancer Outcomes and Satisfaction With Treatment Quality Assessment; enrolled from 2003 through 2006), were used to develop models predicting erectile function 2 years after treatment. A community-based cohort (community-based Cancer of the Prostate Strategic Urologic Research Endeavor [CaPSURE]; enrolled 1995 through 2007) externally validated model performance. Patients in US academic and community-based practices whose HRQOL was measured pretreatment (N ⫽ 1201) underwent follow-up after prostatectomy, external radiotherapy, or brachytherapy for prostate cancer. Sexual outcomes among men completing 2 years’ follow-up (n ⫽ 1027) were used to develop models predicting erectile function that were externally validated among 1913 patients in a community-based cohort. Main Outcome Measures: Patient-reported functional erections suitable for intercourse 2 years following prostate cancer treatment. Results: Two years after prostate cancer treatment, 368 (37% [95% CI, 34%– 40%]) of all patients and 335 (48% [95% CI, 45%–52%]) of those with functional erections prior to treatment reported functional erections; 531 (53% [95% CI, 50%–56%]) of patients without penile prostheses reported use of medications or other devices for erectile dysfunction. Pretreatment sexual HRQOL score, age, serum prostate-specific antigen level, race/ethnicity, body mass index, and intended treatment details were associated with functional erections 2 years after treatment. Multivariable logistic regression models predicting erectile function estimated 2-year function probabilities from as low as 10% or less to as high as 70% or greater depending on the individual’s pretreatment patient characteristics and treatment details. The models performed well in predicting erections in external validation among CaPSURE cohort patients (areas under the receiver operating characteristic curve, 0.77 [95% CI, 0.74 – 0.80] for prostatectomy; 0.87 [95% CI, 0.80 – 0.94] for external radiotherapy; and 0.90 [95% CI, 0.85– 0.95] for brachytherapy). Conclusion: Stratification by pretreatment patient characteristics and treatment details enables prediction of erectile function 2 years after prostatectomy, external radiotherapy, or brachytherapy for prostate cancer. Editorial Comments: This paper provides some new insights into factors that influence recovery of sexual function following treatments for prostate cancer. For example in men undergoing surgery or external radiation preoperative prostate specific antigen (PSA) was found to be a significant factor associated with recovery, presumably because it reflects the extent of disease. For example for men in their fifties with normal 0022-5347/12/1876-2094/0 THE JOURNAL OF UROLOGY® © 2012 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
2094
www.jurology.com
AND
RESEARCH, INC.
Vol. 187, 2094-2100, June 2012 Printed in U.S.A. DOI:10.1016/j.juro.2012.03.038
PROSTATE CANCER
2095
sexual function who were felt to be candidates for bilateral nerve sparing if their PSA was less than 10 ng/ml the likelihood of functional erections 2 years postoperatively was 70% vs 50% if their PSA was greater than 10 ng/ml. For the same patient with nonnerve sparing surgery the comparable numbers were 39% and 21%. For men undergoing external beam radiotherapy if the pretreatment PSA level was more or less than 4 ng/ml, the chances were 92% vs 79%. PSA did not appear to be predictive for patients undergoing brachytherapy. Instead, here preoperative body mass index (BMI) influenced recovery. For a 60-year-old black man with normal sexual function preoperatively if his BMI was less than 25, his chance of functional erections 2 years following treatment was 98% vs 81% if his BMI was greater than or equal to 35. Patrick C. Walsh, M.D.
This multicenter study contains a wealth of information regarding 2-year outcomes following radical prostatectomy or radiation. Pretreatment patient characteristics, sexual HRQOL and treatment details measured in a longitudinal academic multicenter cohort (Prostate Cancer Outcomes and Satisfaction With Treatment Quality Assessment, enrolled from 2003 through 2006) were used to develop models predicting erectile function 2 years after treatment. A community based cohort (community based CaPSURE, enrolled 1995 through 2007) externally validated model performance. A total of 1,201 patients in United States academic and community based practices whose HRQOL was measured before treatment underwent followup after prostatectomy, external radiotherapy or brachytherapy for prostate cancer. Sexual outcomes among 1,027 men completing 2 years of followup were used to develop models predicting erectile function that were externally validated among 1,913 patients in a community based cohort. At 2 years after treatment erectile dysfunction was reported by 619 of 987 men (63%, 95% CI 60 – 66), including 334 of 511 (65%, 95% CI 61– 69) in the prostatectomy group, 145 of 229 (63%, 95% CI 57–70) in the external radiotherapy group and 140 of 247 (57%, 95% CI 50 – 63) in the brachytherapy group. Among men who were potent before treatment 248 of 414 (60%, 95% CI 55– 65) in the prostatectomy group, 51 of 121 (42%, 95% CI 33–51) in the external radiotherapy group and 59 of 158 (37%, 95% CI 30 – 45) in the brachytherapy group reported ED. The ability to attain functional erections suitable for intercourse at 2 years after treatment was reported among 177 of 511 men (35%, 95% CI 30 –39) who underwent prostatectomy. In univariable analyses younger age, fewer comorbid conditions, lower PSA level, lower cancer severity/risk category, pretreatment potency, better (higher) pretreatment EPIC-26 (Expanded Prostate Cancer Index Composite) sexual HRQOL score, better (lower) pretreatment American Urological Association Symptom Index and plan for nerve sparing surgical technique were associated with greater probability of attaining functional erections at 2 years (all p ⴝ 0.05), while association of prostate size with sexual outcome was not statistically significant (p ⴝ 0.07). In multivariable analysis younger age, lower PSA level, better pretreatment sexual functioning score and nerve sparing surgery were associated with increased log odds of functional erections (all p ⴝ 0.05, AUC 0.77, 95% CI 0.72– 0.82). The log odds of erectile function increased approximately linearly with decreasing age and with increasing pretreatment sexual functioning score. The ability to attain functional erections suitable for intercourse at 2 years after treatment was reported among 84 of 229 men (37%, 95% CI 30 – 43) who opted for external radiotherapy as primary therapy. In univariable analyses younger age, lower PSA level, lower risk category, better pretreatment sexual functioning score, better pretreatment American Urological Association Symptom Index and no use of neoadjuvant hormone therapy were associated with greater probability of functional erections 2 years after treatment (all p <0.05). In multivariable analysis lower PSA level, better pretreatment sexual functioning score and no use of neoadjuvant hormone therapy were associated with
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increased log odds of functional erections after treatment (all p <0.05, AUC 0.83, 95% CI 0.78 – 0.88). The log odds of functional erections increased approximately linearly with increasing pretreatment sexual HRQOL score. The ability to attain functional erections suitable for intercourse at 2 years was reported among 107 of 247 men (43%, 95% CI 37–50) who opted for brachytherapy as primary treatment. In univariable analyses younger age, college graduate status, fewer comorbid conditions and better pretreatment sexual HRQOL score were associated with greater probability of functional erections 2 years after treatment (all p <0.05). In multivariable analysis better pretreatment sexual HRQOL score, younger age, black race/ethnicity and lower body mass index were associated with increased log odds of better erectile function (all p <0.05, AUC 0.89, 95% CI 0.85– 0.94). The log odds of erectile function 2 years after treatment increased approximately linearly with increasing pretreatment sexual HRQOL score and decreased approximately linearly with increasing age. The common theme in this study and the subsequent reports is that age, premorbid erectile function and a nerve sparing procedure all seem to be associated with better erectile function following radical prostatectomy, external beam radiation therapy or brachytherapy. Allen D. Seftel, M.D.
Re: Prostate Cancer in the Elderly: Frequency of Advanced Disease at Presentation and Disease-Specific Mortality E. Scosyrev, E. M. Messing, S. Mohile, D. Golijanin and G. Wu Department of Urology, University of Rochester Medical Center, Rochester, New York Cancer 2011; Epub ahead of print.
Background: The objectives of this study were to determine the frequency of metastatic (M1) prostate cancer (PC) at presentation in different age groups, to examine the association of age with PC-specific mortality, and to calculate the relative contribution of different age groups to the pool of M1 cases and PC deaths. Methods: Records from 464,918 patients who were diagnosed with PC from 1998 to 2007 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The patients were categorized according to age into groups ages ⬍50 years, 50 to 54 years, 55 to 59 years, 60 to 64 years, 65 to 69 years, 70 to 74 years, 75 to 79 years, 80 to 84 years, 85 to 89 years, and ⱖ90 years. The cumulative incidence of death from PC was computed using the Gray method. Results: The frequency of M1 PC at presentation was 3% for the group aged ⬍75 years, 5% for the group ages 75 to 79 years, 8% for the group ages 80 to 84 years, 13% for the group ages 85 to 89 years, and 17% for the group aged ⱖ90 years. The 5-year cumulative incidence of death from PC was 3% to 4% for all patients with PC in any category aged ⬍75 years, 7% for patients ages 75 to 79 years, 13% for patients ages 80 to 84 years, 20% for patients ages 85 to 89 years, and 30% for patients aged ⱖ90 years. Although patients aged ⱖ75 years at PC diagnosis represented just over a quarter (26%) of all PC cases, they contributed almost half (48%) of all M1 cases and more than half (53%) of all PC deaths. Conclusions: Compared with younger patients (aged ⬍75 years), older patients were more likely to present with very advanced disease, had a greater risk of death from PC despite higher death rates from competing causes, and contributed more than half of all PC deaths. Awareness of this issue may improve future outcomes for elderly patients with PC. Editorial Comment: It was once believed that when prostate cancer was diagnosed in older men, it was usually slow growing and these patients would die of some other cause. More recently it has become clear that prostate cancer in older men is more likely to be aggressive, and this paper provides some startling statistics. For example men who were diagnosed with prostate cancer after the age of 75 represented almost half of all prostate cancer deaths. For men diagnosed with prostate cancer between ages 75 and 79 only 5% died of prostate cancer over the next 5 years. In contrast, in men diagnosed at age 90 almost 30% had died of the disease 5 years later. If we are told to stop prostate specific
Urological Oncology: Prostate Cancer Re: Prediction of Erectile Function Following Treatment for Prostate Cancer M. Alemozaffar, M. M. Regan, M. R. Cooperberg, J. T. Wei, J. M. Michalski, H. M. Sandler, L. Hembroff, N. Sadetsky, C. S. Saigal, M. S. Litwin, E. Klein, A. S. Kibel, D. A. Hamstra, L. L. Pisters, D. A. Kuban, I. D. Kaplan, D. P. Wood, J. Ciezki, R. L. Dunn, P. R. Carroll and M. G. Sanda Urology Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts JAMA 2011; 306: 1205–1214.
Context: Sexual function is the health-related quality of life (HRQOL) domain most commonly impaired after prostate cancer treatment; however, validated tools to enable personalized prediction of erectile dysfunction after prostate cancer treatment are lacking. Objective: To predict long-term erectile function following prostate cancer treatment based on individual patient and treatment characteristics. Design: Pretreatment patient characteristics, sexual HRQOL, and treatment details measured in a longitudinal academic multicenter cohort (Prostate Cancer Outcomes and Satisfaction With Treatment Quality Assessment; enrolled from 2003 through 2006), were used to develop models predicting erectile function 2 years after treatment. A community-based cohort (community-based Cancer of the Prostate Strategic Urologic Research Endeavor [CaPSURE]; enrolled 1995 through 2007) externally validated model performance. Patients in US academic and community-based practices whose HRQOL was measured pretreatment (N ⫽ 1201) underwent follow-up after prostatectomy, external radiotherapy, or brachytherapy for prostate cancer. Sexual outcomes among men completing 2 years’ follow-up (n ⫽ 1027) were used to develop models predicting erectile function that were externally validated among 1913 patients in a community-based cohort. Main Outcome Measures: Patient-reported functional erections suitable for intercourse 2 years following prostate cancer treatment. Results: Two years after prostate cancer treatment, 368 (37% [95% CI, 34%– 40%]) of all patients and 335 (48% [95% CI, 45%–52%]) of those with functional erections prior to treatment reported functional erections; 531 (53% [95% CI, 50%–56%]) of patients without penile prostheses reported use of medications or other devices for erectile dysfunction. Pretreatment sexual HRQOL score, age, serum prostate-specific antigen level, race/ethnicity, body mass index, and intended treatment details were associated with functional erections 2 years after treatment. Multivariable logistic regression models predicting erectile function estimated 2-year function probabilities from as low as 10% or less to as high as 70% or greater depending on the individual’s pretreatment patient characteristics and treatment details. The models performed well in predicting erections in external validation among CaPSURE cohort patients (areas under the receiver operating characteristic curve, 0.77 [95% CI, 0.74 – 0.80] for prostatectomy; 0.87 [95% CI, 0.80 – 0.94] for external radiotherapy; and 0.90 [95% CI, 0.85– 0.95] for brachytherapy). Conclusion: Stratification by pretreatment patient characteristics and treatment details enables prediction of erectile function 2 years after prostatectomy, external radiotherapy, or brachytherapy for prostate cancer. Editorial Comments: This paper provides some new insights into factors that influence recovery of sexual function following treatments for prostate cancer. For example in men undergoing surgery or external radiation preoperative prostate specific antigen (PSA) was found to be a significant factor associated with recovery, presumably because it reflects the extent of disease. For example for men in their fifties with normal 0022-5347/12/1876-2094/0 THE JOURNAL OF UROLOGY® © 2012 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
2094
www.jurology.com
AND
RESEARCH, INC.
Vol. 187, 2094-2100, June 2012 Printed in U.S.A. DOI:10.1016/j.juro.2012.03.038
PROSTATE CANCER
2095
sexual function who were felt to be candidates for bilateral nerve sparing if their PSA was less than 10 ng/ml the likelihood of functional erections 2 years postoperatively was 70% vs 50% if their PSA was greater than 10 ng/ml. For the same patient with nonnerve sparing surgery the comparable numbers were 39% and 21%. For men undergoing external beam radiotherapy if the pretreatment PSA level was more or less than 4 ng/ml, the chances were 92% vs 79%. PSA did not appear to be predictive for patients undergoing brachytherapy. Instead, here preoperative body mass index (BMI) influenced recovery. For a 60-year-old black man with normal sexual function preoperatively if his BMI was less than 25, his chance of functional erections 2 years following treatment was 98% vs 81% if his BMI was greater than or equal to 35. Patrick C. Walsh, M.D.
This multicenter study contains a wealth of information regarding 2-year outcomes following radical prostatectomy or radiation. Pretreatment patient characteristics, sexual HRQOL and treatment details measured in a longitudinal academic multicenter cohort (Prostate Cancer Outcomes and Satisfaction With Treatment Quality Assessment, enrolled from 2003 through 2006) were used to develop models predicting erectile function 2 years after treatment. A community based cohort (community based CaPSURE, enrolled 1995 through 2007) externally validated model performance. A total of 1,201 patients in United States academic and community based practices whose HRQOL was measured before treatment underwent followup after prostatectomy, external radiotherapy or brachytherapy for prostate cancer. Sexual outcomes among 1,027 men completing 2 years of followup were used to develop models predicting erectile function that were externally validated among 1,913 patients in a community based cohort. At 2 years after treatment erectile dysfunction was reported by 619 of 987 men (63%, 95% CI 60 – 66), including 334 of 511 (65%, 95% CI 61– 69) in the prostatectomy group, 145 of 229 (63%, 95% CI 57–70) in the external radiotherapy group and 140 of 247 (57%, 95% CI 50 – 63) in the brachytherapy group. Among men who were potent before treatment 248 of 414 (60%, 95% CI 55– 65) in the prostatectomy group, 51 of 121 (42%, 95% CI 33–51) in the external radiotherapy group and 59 of 158 (37%, 95% CI 30 – 45) in the brachytherapy group reported ED. The ability to attain functional erections suitable for intercourse at 2 years after treatment was reported among 177 of 511 men (35%, 95% CI 30 –39) who underwent prostatectomy. In univariable analyses younger age, fewer comorbid conditions, lower PSA level, lower cancer severity/risk category, pretreatment potency, better (higher) pretreatment EPIC-26 (Expanded Prostate Cancer Index Composite) sexual HRQOL score, better (lower) pretreatment American Urological Association Symptom Index and plan for nerve sparing surgical technique were associated with greater probability of attaining functional erections at 2 years (all p ⴝ 0.05), while association of prostate size with sexual outcome was not statistically significant (p ⴝ 0.07). In multivariable analysis younger age, lower PSA level, better pretreatment sexual functioning score and nerve sparing surgery were associated with increased log odds of functional erections (all p ⴝ 0.05, AUC 0.77, 95% CI 0.72– 0.82). The log odds of erectile function increased approximately linearly with decreasing age and with increasing pretreatment sexual functioning score. The ability to attain functional erections suitable for intercourse at 2 years after treatment was reported among 84 of 229 men (37%, 95% CI 30 – 43) who opted for external radiotherapy as primary therapy. In univariable analyses younger age, lower PSA level, lower risk category, better pretreatment sexual functioning score, better pretreatment American Urological Association Symptom Index and no use of neoadjuvant hormone therapy were associated with greater probability of functional erections 2 years after treatment (all p <0.05). In multivariable analysis lower PSA level, better pretreatment sexual functioning score and no use of neoadjuvant hormone therapy were associated with
2096
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increased log odds of functional erections after treatment (all p <0.05, AUC 0.83, 95% CI 0.78 – 0.88). The log odds of functional erections increased approximately linearly with increasing pretreatment sexual HRQOL score. The ability to attain functional erections suitable for intercourse at 2 years was reported among 107 of 247 men (43%, 95% CI 37–50) who opted for brachytherapy as primary treatment. In univariable analyses younger age, college graduate status, fewer comorbid conditions and better pretreatment sexual HRQOL score were associated with greater probability of functional erections 2 years after treatment (all p <0.05). In multivariable analysis better pretreatment sexual HRQOL score, younger age, black race/ethnicity and lower body mass index were associated with increased log odds of better erectile function (all p <0.05, AUC 0.89, 95% CI 0.85– 0.94). The log odds of erectile function 2 years after treatment increased approximately linearly with increasing pretreatment sexual HRQOL score and decreased approximately linearly with increasing age. The common theme in this study and the subsequent reports is that age, premorbid erectile function and a nerve sparing procedure all seem to be associated with better erectile function following radical prostatectomy, external beam radiation therapy or brachytherapy. Allen D. Seftel, M.D.
Re: Prostate Cancer in the Elderly: Frequency of Advanced Disease at Presentation and Disease-Specific Mortality E. Scosyrev, E. M. Messing, S. Mohile, D. Golijanin and G. Wu Department of Urology, University of Rochester Medical Center, Rochester, New York Cancer 2011; Epub ahead of print.
Background: The objectives of this study were to determine the frequency of metastatic (M1) prostate cancer (PC) at presentation in different age groups, to examine the association of age with PC-specific mortality, and to calculate the relative contribution of different age groups to the pool of M1 cases and PC deaths. Methods: Records from 464,918 patients who were diagnosed with PC from 1998 to 2007 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The patients were categorized according to age into groups ages ⬍50 years, 50 to 54 years, 55 to 59 years, 60 to 64 years, 65 to 69 years, 70 to 74 years, 75 to 79 years, 80 to 84 years, 85 to 89 years, and ⱖ90 years. The cumulative incidence of death from PC was computed using the Gray method. Results: The frequency of M1 PC at presentation was 3% for the group aged ⬍75 years, 5% for the group ages 75 to 79 years, 8% for the group ages 80 to 84 years, 13% for the group ages 85 to 89 years, and 17% for the group aged ⱖ90 years. The 5-year cumulative incidence of death from PC was 3% to 4% for all patients with PC in any category aged ⬍75 years, 7% for patients ages 75 to 79 years, 13% for patients ages 80 to 84 years, 20% for patients ages 85 to 89 years, and 30% for patients aged ⱖ90 years. Although patients aged ⱖ75 years at PC diagnosis represented just over a quarter (26%) of all PC cases, they contributed almost half (48%) of all M1 cases and more than half (53%) of all PC deaths. Conclusions: Compared with younger patients (aged ⬍75 years), older patients were more likely to present with very advanced disease, had a greater risk of death from PC despite higher death rates from competing causes, and contributed more than half of all PC deaths. Awareness of this issue may improve future outcomes for elderly patients with PC. Editorial Comment: It was once believed that when prostate cancer was diagnosed in older men, it was usually slow growing and these patients would die of some other cause. More recently it has become clear that prostate cancer in older men is more likely to be aggressive, and this paper provides some startling statistics. For example men who were diagnosed with prostate cancer after the age of 75 represented almost half of all prostate cancer deaths. For men diagnosed with prostate cancer between ages 75 and 79 only 5% died of prostate cancer over the next 5 years. In contrast, in men diagnosed at age 90 almost 30% had died of the disease 5 years later. If we are told to stop prostate specific