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Testosterone slows prostate cancer recurrence in low-risk patients

17-03-2019 10:13
Background
Doctors have long regarded testosterone as a hormone which promotes prostate cancer. The 1941 work of Huggins and Hodges won Huggins the 1966 Nobel Prize for Medicine*, for reporting the dramatic impact of testosterone reduction on prostate cancer. Since then, medicines which reduce levels of the hormone testosterone have become a standard option for many patients**.

However, in the late 1990s to 2000s, doctors discovered that although men on long term anti-testosterone treatments were not dying from prostate cancer, they were dying prematurely of cardiovascular diseaseIt seemed that although anti-testosterone therapies were treating the prostate cancer, the extremely low testosterone levels were significantly worsening metabolic complications such as elevated blood sugar, diabetes, elevated cholesterol, mid-abdomen visceral fat, etc. Low testosterone also caused a loss of sexual function in many men on anti-androgen treatment. This led some doctors*** to suggest testosterone treatment of some low risk men after radiation or surgical treatment.

What have they done?
Starting in 2008 a team of doctors from the University of California, Irvine, led by Professor Thomas Ahlering, began to carefully select patients for testosterone replacement after primary treatment of prostate cancer with robotic radical prostatectomy, in hopes of improving recovery of sexual function.

The team worked with 834 patients undergoing radical prostatectomy. They treated 152 low-risk patients with no evidence of disease with testosterone replacement therapy. After a median of 3.1 years following surgery, they tested the patients for biochemical recurrence of the cancer, as indicated by measurement of the Prostate Specific Antigen (PSA) levels. They found that the cancer had recurred in only approximately 5% of treated patients, whereas the cancer had recurred in 15% of the patients who did not receive testosterone. Overall, after accounting for differences between the groups, they found nearly a three-fold reduction by three years.

Importance
Thomas Ahlering commented “This is not what we set out to prove, so it was a big surprise: not only did testosterone replacement not increase recurrence, but it actually lowered recurrence rates. While the testosterone is not curing the cancer per se, it is slowing the growth of the cancer, giving an average of an extra 1.5 years before traces of cancer can be found. We already know that testosterone can help with physiological markers such as muscle mass, better cholesterol and triglyceride levels and increased sexual activity, so this seems to be a win-win”.

He continued, “There have been smaller studies which have hinted that testosterone may not be risky for certain patient groups, but this is the largest such study ever conducted. We’re not suggesting that treatment methods be changed just yet, but this puts us at the stage where we need to question the taboo against testosterone use in prostate cancer therapy – especially for low-risk patients after radical prostatectomy. We need the oncology/urology community to begin to review testosterone use”.

Commenting, Professor Francesco Montorsi (Milano), European Association of Urology’s Adjunct Secretary General for Science said:
The paper is indeed important, as it stresses the importance of checking testosterone levels as a part of the management of patients with sexual disorders following radical prostatectomy. Obviously selection of the right patients is vital, but if confirmed, this may have immediate benefits on quality of life; the possibility of reducing mortality would be an unexpected bonus. We now need bigger studies to support this work”.

This is an independent comment; Professor Montorsi was not involved in this work.

Notes
*See Nobel citation https://www.nobelprize.org/prizes/medicine/1966/huggins/facts/  
**For background on hormonal treatment see https://www.cancer.org/cancer/prostate-cancer/treating/hormone-therapy.html
***notably Dr Abraham Morgentaler
 
Funding: no external funding was received in support of this work.

ENDS
 

 

The 34th European Association of Urology conference takes place in Barcelona from 15th to 19th March 2019. This is the largest and most important urology congress in Europe, with up to 14,000 expected to attend. Conference website https://eaucongress.uroweb.org/  

Contact details
Professor Thomas Ahlering tahlerin@uci.edu
Professor Francesco Montorsi montorsi.francesco@hsr.it
EAU Press Officer, Tom Parkhill: tom@parkhill.ittelephone +39 349 238 8191

Conference abstract: Testosterone replacement therapy prevents disease progression in men undergoing radical prostatectomy

Authors
Towe M. , Huynh L.M. , El-Khatib F.M. , Yafi F.A. , Ahlering T.
University of California, Dept. of Urology, Irvine, Orange, United States of America

Introduction & Objectives
The use of testosterone replacement therapy (TRT) is currently not recommended in patients with a history of prostate cancer. However, recent data has shown that higher levels of free testosterone (FT) are associated with lower grade cancers, and may be protective against early biochemical recurrence (BCR). We present a study examining the use of TRT in patients with prostate cancer undergoing radical prostatectomy (RP) and its effect on disease progression.

Materials & Methods
850 patients who underwent robot-assisted RP for primary treatment of localized prostate cancer by a single surgeon between December 2009 and June 2018 were included. Prostate Specific Antigen (PSA), pathological grade, and pathological stage were prospectively collected. Post-operative PSA levels were used to assess BCR status (defined as 2 consecutive PSA values of 0.2 ng/dL or greater). Median follow up time after RARP was 2.75 years. Univariate and multivariate comparisons between patients on TRT and those not on TRT were used to assess differences in rates of BCR and time to BCR. Patients in the TRT group remained on TRT up untildate of last follow up or until date of BCR.

Results
Out of 850 patients, 834 had values recorded for all pre-specified variables and 152 (18.2%) were treated with TRT. Of the patients on TRT, 15/152 (9.9%) developed BCR compared with 160/682 (23.5%) patients in the group not on TRT (p<0.001). Overall, 85 patients experienced BCR within a year after surgery, and 4 (4.7%) of those patients were on TRT compared to 81 (95.3%) not on TRT (p<0.0001). In multivariate analysis, being placed on TRT predicted a longer time to BCR and delayed progression by a median of 1.5 years, after adjusting for pathological grade and stage (p=0.005).

Conclusions
The use of TRT in patients with prostate cancer was shown to be beneficial by delaying time to BCR. In all patients that experienced BCR, those that were on TRT had a median 1.5 year longer latency of disease progression. These results provide further evidence that testosterone replacement may be beneficial in prostate cancer patients.

 
 
 
 

 

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