Vol. 41 (6): 1167-1171, November . December, 2015 doi: 10.1590/S1677-5538.IBJU.2014.0528
ORIGINAL ARTICLE
Outcomes of Prostate Biopsy in Men with Hypogonadism Prior or During Testosterone Replacement Therapy _______________________________________________ Daniel A Shoskes 1, Yagil Barazani 1, Khaled Fareed 1, Edmund Sabanegh Jr. 1 Department of Urology, Glickman Urological and Kidney Institute, The Cleveland Clinic, Cleveland, OH, USA 1
ABSTRACT ARTICLE INFO ______________________________________________________________
______________________
Introduction: The relationship between Testosterone Replacement Therapy (TRT) and prostate cancer remains controversial. Most TRT studies show no change in prostate specific antigen (PSA) but some men do have PSA rise or develop an abnormal digital rectal exam (aDRE). Our objective was to examine the biopsy results of men with symptomatic hypogonadism before or during therapy. Materials and Methods: Data was extracted from our medical record on men with hypogonadism who had a prostate biopsy within the past 4 years done by 3 Urologists with guideline driven practice patterns. Results: 96 men were identified. Mean age at biopsy was 63 (range 40-85) and median PSA was 3.78ng/dL (0.5-662). Of the 61 men not on TRT, median PSA was 4.34 (0.5 to 662) and mean total testosterone 254 (191-341). There were 29 (47.5%) prostate cancers found (6 Gleason score 6, 13 Gleason score 7, 10 Gleason score 8 or 9). Of the 35 men on TRT, median PSA was 3.27 (0.5 to 13.7). The %PSA increase ranged from 2 to 251% (mean 93.5%). Mean total testosterone was 383 (146-792). Of the 14 men treated < 2 years, none had cancer. Of the 21 men treated 2 or more years 5 had cancer (2 Gleason score 6, 3 Gleason score 7). Conclusions: Men with hypogonadism and a clinical indication for biopsy often have prostate cancer, many high grade. No men with an initial PSA rise on TRT had cancer. Men on long term TRT should be monitored with PSA and DRE per guidelines.
Key words: Hypogonadism; Testosterone; Biopsy
INTRODUCTION The interaction between Testosterone Replacement Therapy (TRT), hypogonadism and prostate cancer remains controversial. While prostate cancer has remained a contraindication in the package insert of TRT formulations, an emerging body of evidence suggests that TRT does not increase the risk of developing prostate cancer (1), is safe following therapy for prostate cancer (2) and may be safe during active surveillance of prostate cancer (3). Current guide-
Int Braz J Urol. 2015; 41: 1167-71
_____________________ Submitted for publication: October 22, 2014 _____________________ Accepted after revision: March 14, 2015
lines recommend measuring testosterone prior to starting TRT and age appropriate monitoring of Prostate Specific Antigen (PSA) and digital rectal exam before and during therapy (4). Anecdotal evidence so far in North America is that these guideline recommendations are often not followed (5). In studies of TRT, mean PSA usually remains stable (6) or rises slightly (7). Nevertheless, individual patients may have a significant jump in PSA after starting TRT which is concerning for prostate cancer and often
1167
ibju | Prostate Biopsy in Hypogonadism
prompts a prostate biopsy. We have not found any published studies to date that address how often these patients are found to actually have prostate cancer in this clinical scenario. AIM To study the results of prostate biopsy in men with a diagnosis of hypogonadism, comparing the outcomes both prior to and after starting TRT, with an emphasis on men whose PSA rapidly rises following initiation of therapy. MATERIALS AND METHODS Under an Institutional Review Board approved protocol we retrospectively extracted data from the Cleveland Clinic electronic medical record of patients with a prostate biopsy done between 2010 to 2014 with a concurrent clinical diagnosis of hypogonadism (CPT 257.2). We focused on patients cared for by three urologists specialized in the evaluation and treatment of men with low testosterone and who all follow common clinical guidelines for diagnosis, treatment and monitoring (4). Initially 125 men were identified. Following individual chart review 29 men were excluded for reasons such as prior prostate cancer, incorrect diagnosis or missing data. This left 96 patients for analysis. Data collected included age, initial PSA, prior PSA, initial morning total testosterone, testosterone after therapy (most recent value prior to biopsy), duration of therapy and pathology of biopsy including Gleason score. Men on testosterone therapy received a variety of agents including injections, topical gels and implantable subcutaneous pellets. All patients had a minimum of 12 cores taken for pathology and graded according to the latest Gleason score. The study period predates our use of MRI-fusion biopsy. Data was analyzed using Prism 5.0 for Mac (GraphPad). Continuous variables were compared by t test or ANOVA when parametric and Mann-Whitney or Kruskal-Wallis test when non-parametric. Categorical outcomes were compared by the Chi squared test with Fischer correction. All tests were double sided. Statistical significance was set at P
ORIGINAL ARTICLE
Outcomes of Prostate Biopsy in Men with Hypogonadism Prior or During Testosterone Replacement Therapy _______________________________________________ Daniel A Shoskes 1, Yagil Barazani 1, Khaled Fareed 1, Edmund Sabanegh Jr. 1 Department of Urology, Glickman Urological and Kidney Institute, The Cleveland Clinic, Cleveland, OH, USA 1
ABSTRACT ARTICLE INFO ______________________________________________________________
______________________
Introduction: The relationship between Testosterone Replacement Therapy (TRT) and prostate cancer remains controversial. Most TRT studies show no change in prostate specific antigen (PSA) but some men do have PSA rise or develop an abnormal digital rectal exam (aDRE). Our objective was to examine the biopsy results of men with symptomatic hypogonadism before or during therapy. Materials and Methods: Data was extracted from our medical record on men with hypogonadism who had a prostate biopsy within the past 4 years done by 3 Urologists with guideline driven practice patterns. Results: 96 men were identified. Mean age at biopsy was 63 (range 40-85) and median PSA was 3.78ng/dL (0.5-662). Of the 61 men not on TRT, median PSA was 4.34 (0.5 to 662) and mean total testosterone 254 (191-341). There were 29 (47.5%) prostate cancers found (6 Gleason score 6, 13 Gleason score 7, 10 Gleason score 8 or 9). Of the 35 men on TRT, median PSA was 3.27 (0.5 to 13.7). The %PSA increase ranged from 2 to 251% (mean 93.5%). Mean total testosterone was 383 (146-792). Of the 14 men treated < 2 years, none had cancer. Of the 21 men treated 2 or more years 5 had cancer (2 Gleason score 6, 3 Gleason score 7). Conclusions: Men with hypogonadism and a clinical indication for biopsy often have prostate cancer, many high grade. No men with an initial PSA rise on TRT had cancer. Men on long term TRT should be monitored with PSA and DRE per guidelines.
Key words: Hypogonadism; Testosterone; Biopsy
INTRODUCTION The interaction between Testosterone Replacement Therapy (TRT), hypogonadism and prostate cancer remains controversial. While prostate cancer has remained a contraindication in the package insert of TRT formulations, an emerging body of evidence suggests that TRT does not increase the risk of developing prostate cancer (1), is safe following therapy for prostate cancer (2) and may be safe during active surveillance of prostate cancer (3). Current guide-
Int Braz J Urol. 2015; 41: 1167-71
_____________________ Submitted for publication: October 22, 2014 _____________________ Accepted after revision: March 14, 2015
lines recommend measuring testosterone prior to starting TRT and age appropriate monitoring of Prostate Specific Antigen (PSA) and digital rectal exam before and during therapy (4). Anecdotal evidence so far in North America is that these guideline recommendations are often not followed (5). In studies of TRT, mean PSA usually remains stable (6) or rises slightly (7). Nevertheless, individual patients may have a significant jump in PSA after starting TRT which is concerning for prostate cancer and often
1167
ibju | Prostate Biopsy in Hypogonadism
prompts a prostate biopsy. We have not found any published studies to date that address how often these patients are found to actually have prostate cancer in this clinical scenario. AIM To study the results of prostate biopsy in men with a diagnosis of hypogonadism, comparing the outcomes both prior to and after starting TRT, with an emphasis on men whose PSA rapidly rises following initiation of therapy. MATERIALS AND METHODS Under an Institutional Review Board approved protocol we retrospectively extracted data from the Cleveland Clinic electronic medical record of patients with a prostate biopsy done between 2010 to 2014 with a concurrent clinical diagnosis of hypogonadism (CPT 257.2). We focused on patients cared for by three urologists specialized in the evaluation and treatment of men with low testosterone and who all follow common clinical guidelines for diagnosis, treatment and monitoring (4). Initially 125 men were identified. Following individual chart review 29 men were excluded for reasons such as prior prostate cancer, incorrect diagnosis or missing data. This left 96 patients for analysis. Data collected included age, initial PSA, prior PSA, initial morning total testosterone, testosterone after therapy (most recent value prior to biopsy), duration of therapy and pathology of biopsy including Gleason score. Men on testosterone therapy received a variety of agents including injections, topical gels and implantable subcutaneous pellets. All patients had a minimum of 12 cores taken for pathology and graded according to the latest Gleason score. The study period predates our use of MRI-fusion biopsy. Data was analyzed using Prism 5.0 for Mac (GraphPad). Continuous variables were compared by t test or ANOVA when parametric and Mann-Whitney or Kruskal-Wallis test when non-parametric. Categorical outcomes were compared by the Chi squared test with Fischer correction. All tests were double sided. Statistical significance was set at P
