Does Testosterone Therapy Worsen Prostate Cancer Progression?

MedicalResearch.com Interview with:
Ryan Flannigan MD FRCSC
PGY 5 Urology Resident
Department of Urological Sciences
University of British Columbia

MedicalResearch.com: What is the background for this study?

Dr. Flannigan: In the aging population the incidence of both prostate cancer and testosterone deficiency (TD) increase and even overlap in many patients. However, since Huggins’ original research in 1940, we have understood that prostate cancer is largely regulated by the androgen receptor (AR). Thus, the thought of treating someone with exogenous testosterone (T) was concerning for fear of further activation of the androgen receptor, and therefore promoting prostate cancer growth. However, further research has continued to add clarity to this complex interaction between androgens and the prostate. The saturation theory describes the observation that prostate specific antigen (PSA) responds to increasing serum testosterone levels only to a value of approximately 8.7nmol/L, with no inflation of PSA beyond these T levels. This is likely not the whole story when it comes to the interaction of T and the prostate, but it does suggest the prostate may not experience changes in cellular function with serum testosterone beyond low levels. It is also understood that prostate cancer requires AR activation to grow but is not caused by AR activation. Thus, we hypothesized that among those with un-treated prostate cancer, ie. patients on active surveillance, would not experience changes in biochemical recurrence (BCR) or changes in disease progression. In addition, we hypothesized that patients with previously treated prostate cancer would not have viable prostate cancer cells and thus, PSA would not increase.

MedicalResearch.com:? What are the main findings? 

Dr. Flannigan: The findings of our study were consistent with our hypothesis. We retrospectively reviewed 82 patients from our local clinical practice with a diagnosis of prostate cancer who had also since received TT. Eight of these patients were on AS with untreated prostate cancer. Seventy four patients had previous definitive therapy including: 22 patients treated with radical prostatectomy (RP), 37 with external beam radiation therapy (EBRT), 13 with brachytherapy (BT), 1 with HIFU, and 1 with cryotherapy. The patients on AS were followed for a median of 27 months, and none have progressed on biopsy or undergone definitive therapy. Two of these patients developed a transient rise in PSA, which led to stopping TT. Upon cessation of TT, PSA values returned to each patient’s respective baseline. PSA values significantly increased following TT overall, but upon subgroup analysis this was due to the low risk patients in the AS group. Thus, those with treated prostate cancer did not have a statistically significant increase in PSA. This may be explained by the saturation theory as the mean T levels prior to therapy were 6.3mmol/L and increased beyond the saturation level of 8.7mmol/L to 13.2mmol/L. No incidences of BCR occurred among the RP patients. Among the radiation therapy patients, 3 (6%) developed BCR. This level of BCR is lower than previous reports in the literature of approximately 22%. These findings are reassuring that the BCR is not largely elevated compared to previous reports but conclusions regarding such small numbers must be reserved. 

MedicalResearch.com: What should clinicians and patients take away from your report 

Dr. Flannigan: The available level of evidence for TT among patients with either active or treated localized prostate cancer is limited to cases series and the limitations have to be respected. However, our findings are consistent with previous reports of the use of TT for symptomatic hypogonadal men with treated or active localized prostate cancer. Testosterone therapy does not appear to increase BCR or disease progression in this patient cohort. We do recommend careful patient selection and very close monitoring of any patient with a history of prostate cancer on TT including PSA.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Dr. Flannigan: The diagnoses of hypogonadism and prostate cancer are intersecting with increased frequency. The present level of evidence for use of TT in patients with prostate cancer, treated or active, is limited to case series. There is a need for prospective cohorts or randomized controlled trials to evaluate the clinical efficacy and safety of TT among patients with localized prostate cancer.

Citation:

Testosterone Therapy In Patients With Treated and Untreated Prostate Cancer: Impact on Oncologic Outcomes

Jesse OryRyan FlanniganColin LundeenJames G. HuangPeter PommervilleS Larry Goldenberg1
Accepted 19 April 2016, Available online 27 April 2016
The Journal of Urology
Available online 27 April 2016

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