madman
Super Moderator
Oncological safety and functional outcomes of testosterone replacement therapy in symptomatic adult‑onset hypogonadal prostate cancer patients following robot‑assisted radical prostatectomy
Abstract
Purpose Testosterone replacement therapy (TRT) remains controversial in men with treated prostate cancer. We assessed its safety and functional impacts in patients after definitive surgical treatment with robotic-assisted radical prostatectomy (RARP).
Methods We performed a retrospective analysis of 1303 patients who underwent RARP during the years 2006–2019. We identified men with symptoms of andropause and low serum testosterone who received TRT post-RARP; then we divided the cohort into two groups accordingly for comparison. Biochemical recurrence (BCR) was the primary endpoint. Secondary endpoints included functional outcomes. Predictors of BCR, including the effect of TRT on BCR, were evaluated using univariable and multivariable logistic regression.
Results Among the forty-seven men who received TRT, the mean age was 60.83 years with a median follow-up of 48 months. Three (6.4%) and 157 (12.56%) patients experienced BCR in TRT and non-TRT groups, respectively. Baseline characteristics were similar between both groups except for higher mean BMI in the TRT group (p=0.03). In the multivariate analysis (MVA), higher pre-RARP prostate-specific antigen (PSA) (p=0.043), higher International Society of Urological Pathology score (p<0.001), seminal vesical invasion (p=0.018), and positive surgical margin (p<0.001) were predictors of BCR. However, TRT was not (p=0.389). In addition, there was a significant change in the Sexual Health Inventory for Men (p=0.022), and serum testosterone level (p<0.001) before and 6 months after initiation of TRT.
Conclusion: Our findings suggest that TRT, in well-selected, closely followed, symptomatic men post-RARP is an oncologically safe and functionally effective treatment in prostate cancer patients post-RARP.
Introduction
Prostate cancer (PCa) is projected to be the most commonly diagnosed cancer in men for the year 2020, with an estimate of 21% of new cases [1]. It is the second leading cause of deaths in males estimated at 10% [1]. Screening and early detection, especially in low-risk disease, have steered towards excellent oncological outcomes allowing surgeons to focus on improving functional endpoints, mainly potency and urinary continence [2, 3].
Hypogonadism or the so-called “late-onset hypogonadism” is the combination of low serum testosterone and androgen deficiency symptoms. Validated clinical tools such as the Androgen Deficiency in Ageing Males (ADAM) questionnaire have been developed to assist during patient counseling [4]. Testosterone replacement therapy (TRT) is the treatment of choice [5]. However, the use of TRT in men with PCa or previously treated PCa has long been controversial. Since Huggins and Hodges Nobel prize-winning observation (1941), which uncovered that castration ameliorated metastatic prostate cancer and its growth are linearly related to testosterone concentration, testosterone was scientifically forbidden from being given to those patients [6].
During the last two decades, “The saturation model”, which describes a level of testosterone above which the androgen receptors in the prostate tissues become saturated and insensitive to androgen stimulation while below which the tissues remain highly sensitive to androgens, challenged previously established conclusions [7, 8]. Indeed, several studies have shown the oncological safety of TRT in elderly men, men treated with external beam radiation, brachytherapy, or radical prostatectomy, and the benefits of TRT on human physiology and psychology [5, 9, 10].
Taking into consideration the scarcity of data relative to patients receiving TRT after robotic-assisted radical prostatectomy (RARP), we aimed to evaluate the oncological safety and functional outcomes in this population.
*Most published studies along with ours have a drawback of being retrospective. This affects patient selection (patient sexuality, partner’s interest, and other medical comorbidities). Nonetheless, our 47 patients are a good addition to this pool of patients who received TRT after RP and our results support those from multiple publications on the track to compile a larger number of patients refecting the TRT’s safety. A promising study to look for is large prospective phase II randomized placebo-controlled trials started in March 2019 looking at TRT in PCa patient after radical prostatectomy (ClinicalTrials.gov Identifier: NCT03716739). Our study has several limitations including those mentioned above (retrospective nature, lack of randomization in patient selection), in addition, to delays in treatment due to patient safety reasons, the short follow-up period that again can be considered longer than most of the previously published literature.
Conclusion
Our study results demonstrate that testosterone replacement therapy can be used safely in patients with prostate cancer after surgical therapy of curative intent with no significant effect on BCR. TRT has improved subjective and objective functional measures in those patients. Meanwhile, TRT should be delivered only to patients who are well informed and closely monitored with serial blood tests and clinical exams.
Abstract
Purpose Testosterone replacement therapy (TRT) remains controversial in men with treated prostate cancer. We assessed its safety and functional impacts in patients after definitive surgical treatment with robotic-assisted radical prostatectomy (RARP).
Methods We performed a retrospective analysis of 1303 patients who underwent RARP during the years 2006–2019. We identified men with symptoms of andropause and low serum testosterone who received TRT post-RARP; then we divided the cohort into two groups accordingly for comparison. Biochemical recurrence (BCR) was the primary endpoint. Secondary endpoints included functional outcomes. Predictors of BCR, including the effect of TRT on BCR, were evaluated using univariable and multivariable logistic regression.
Results Among the forty-seven men who received TRT, the mean age was 60.83 years with a median follow-up of 48 months. Three (6.4%) and 157 (12.56%) patients experienced BCR in TRT and non-TRT groups, respectively. Baseline characteristics were similar between both groups except for higher mean BMI in the TRT group (p=0.03). In the multivariate analysis (MVA), higher pre-RARP prostate-specific antigen (PSA) (p=0.043), higher International Society of Urological Pathology score (p<0.001), seminal vesical invasion (p=0.018), and positive surgical margin (p<0.001) were predictors of BCR. However, TRT was not (p=0.389). In addition, there was a significant change in the Sexual Health Inventory for Men (p=0.022), and serum testosterone level (p<0.001) before and 6 months after initiation of TRT.
Conclusion: Our findings suggest that TRT, in well-selected, closely followed, symptomatic men post-RARP is an oncologically safe and functionally effective treatment in prostate cancer patients post-RARP.
Introduction
Prostate cancer (PCa) is projected to be the most commonly diagnosed cancer in men for the year 2020, with an estimate of 21% of new cases [1]. It is the second leading cause of deaths in males estimated at 10% [1]. Screening and early detection, especially in low-risk disease, have steered towards excellent oncological outcomes allowing surgeons to focus on improving functional endpoints, mainly potency and urinary continence [2, 3].
Hypogonadism or the so-called “late-onset hypogonadism” is the combination of low serum testosterone and androgen deficiency symptoms. Validated clinical tools such as the Androgen Deficiency in Ageing Males (ADAM) questionnaire have been developed to assist during patient counseling [4]. Testosterone replacement therapy (TRT) is the treatment of choice [5]. However, the use of TRT in men with PCa or previously treated PCa has long been controversial. Since Huggins and Hodges Nobel prize-winning observation (1941), which uncovered that castration ameliorated metastatic prostate cancer and its growth are linearly related to testosterone concentration, testosterone was scientifically forbidden from being given to those patients [6].
During the last two decades, “The saturation model”, which describes a level of testosterone above which the androgen receptors in the prostate tissues become saturated and insensitive to androgen stimulation while below which the tissues remain highly sensitive to androgens, challenged previously established conclusions [7, 8]. Indeed, several studies have shown the oncological safety of TRT in elderly men, men treated with external beam radiation, brachytherapy, or radical prostatectomy, and the benefits of TRT on human physiology and psychology [5, 9, 10].
Taking into consideration the scarcity of data relative to patients receiving TRT after robotic-assisted radical prostatectomy (RARP), we aimed to evaluate the oncological safety and functional outcomes in this population.
*Most published studies along with ours have a drawback of being retrospective. This affects patient selection (patient sexuality, partner’s interest, and other medical comorbidities). Nonetheless, our 47 patients are a good addition to this pool of patients who received TRT after RP and our results support those from multiple publications on the track to compile a larger number of patients refecting the TRT’s safety. A promising study to look for is large prospective phase II randomized placebo-controlled trials started in March 2019 looking at TRT in PCa patient after radical prostatectomy (ClinicalTrials.gov Identifier: NCT03716739). Our study has several limitations including those mentioned above (retrospective nature, lack of randomization in patient selection), in addition, to delays in treatment due to patient safety reasons, the short follow-up period that again can be considered longer than most of the previously published literature.
Conclusion
Our study results demonstrate that testosterone replacement therapy can be used safely in patients with prostate cancer after surgical therapy of curative intent with no significant effect on BCR. TRT has improved subjective and objective functional measures in those patients. Meanwhile, TRT should be delivered only to patients who are well informed and closely monitored with serial blood tests and clinical exams.
