ASCO Genitourinary Cancers Symposium (Low testosterone at first PSA failure)

[pjoshea13]

After 14 years of PubMed reading, regarding PCa & testosterone [T], I have at least two strong opinions:

i) men on active surveillance should be offered T replacement [TRT] if T is near or below 350 ng/dL.

ii) men on intermittent ADT [IADT] should be offered TRT to rapidly restore T during the off phase.

"Low testosterone at prostate cancer diagnosis has been associated with a worse prognosis. Whether this is true and how to define the best treatment approach at first PSA failure following definitive therapy and prior to the documentation of metastatic disease has not been elucidated and was studied."

"After a median follow-up of 6.68 years following first PSA failure, 31 men (53.4%) died; 10 from prostate cancer (32.3%), of which 8/11 (72.7%) versus 2/47 (4.3%) occurred in men with low versus normal testosterone at PSA failure, respectively. "

"Low testosterone at first PSA failure confers a very poor prognosis. Given prolonged survival when abiraterone or docetaxel is added to ADT in men with castrate-sensitive metastatic prostate cancer and possibly in men with localized high-risk prostate cancer provides rationale to support their use with ADT in men with low testosterone at PSA failure in the setting of a phase II trial."

-Patrick

45 Poster Session (Board #C9), Thu, 11:30 AM-1:00 PM and

5:15 PM-6:15 PM

Low testosterone at first PSA failure and assessment of the risk of death in men with unfavorable-risk prostate cancer treated on prospective clinical trials.

Katelyn Mae Atkins, Ming-Hui Chen, Jing Wu, Andrew A. Renshaw, Marian Loffredo, Philip W. Kantoff, Eric Jay Small, Anthony Victor D’Amico; Harvard Medical School Radiation Oncology Program/ Dana-Farber Cancer Institute/ Brigham and Women’s Hospital, Boston, MA; University of Connecticut, Storrs, CT; University of Rhode Island, Kingston, RI; Baptist Hospital and Miami Cancer Institute, Miami, FL; Dana-Farber Cancer Institute/ Brigham and Women’s Hospital, Boston, MA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; University of California San Francisco, San Francisco, CA

Background: Low testosterone at prostate cancer diagnosis has been associated with a worse prognosis. Whether this is true and how to define the best treatment approach at first PSA failure following definitive therapy and prior to the documentation of metastatic disease has not been elucidated and was studied.

Methods: Between 1995 to 2001, 58 men with unfavorable-risk prostate cancer treated on clinical trials with radiation and androgen deprivation therapy (ADT) had testosterone levels at PSA failure available. Cox and Fine and Gray regressions were performed to ascertain whether low versus normal testosterone at PSA failure was associated with the risk of prostate cancer-specific, other-cause and all-cause mortality (PCSM, OCM, ACM) adjusting for age, salvage ADT use and known prostate cancer prognostic factors.

Results: After a median follow-up of 6.68 years following first PSA failure, 31 men (53.4%) died; 10 from prostate cancer (32.3%), of which 8/11 (72.7%) versus 2/47 (4.3%) occurred in men with low versus normal testosterone at PSA failure, respectively. A significant increase in the risk of ACM (adjusted hazard ratio, AHR [2.54, 95% CI 1.04-6.21]; P = 0.04) and PCSM (AHR [13.71, 95% CI 2.4-78.16]; P = 0.003), with a reciprocal trend toward decreased risk of OCM (AHR [0.18, 95% CI 0.02-1.55]; P = 0.12) was observed in men with low versus normal testosterone at first PSA failure.

Conclusions: Low testosterone at first PSA failure confers a very poor prognosis. Given prolonged survival when abiraterone or docetaxel is added to ADT in men with castrate-sensitive metastatic prostate cancer and possibly in men with localized high-risk prostate cancer provides rationale to support their use with ADT in men with low testosterone at PSA failure in the setting of a phase II trial.

[eggraj8]

Very interesting. This also raises the question are men with low T being adequately tested for PC in the first place. If they get diagnosed when PC is well established then treatment is less likely to be successful

[pjoshea13 in reply to eggraj8]

It's not clear if men with low T have greater risk for PCa. The problem is that some men with very low T are, in effect on ADT-light, which would delay diagnosis.

But men diagnosed with PCa who have low T are at greater risk for more serious disease.

Low T (usually accompanied with higher estradiol [E2]) is a risk factor for other conditions too, & I do think that T should be monitored by one's GP.

it's really a sad situation, since with early T replacement, PCa cells might become indolent.

-Patrick

[eggraj8 in reply to pjoshea13]

I am wondering if the measured low T is actually due to the cancer in the prostate taking the testosterone out of the blood so it is reduced. The testosterone would appear to be low even though it was produced at a higher possibly normal rate. High estradiol may be a controlling factor in T production. Other men with normal estradiol may compensate for any testosterone depletion due to PC by increasing production in the testicles. If this were the case then giving testosterone replacement would be harmful to those men because it would make testosterone more available to the PC.

Your Low T and high estradiol risk factor makes lots of sense from what I understand. i am just not clear that early T replacement is a solution.

[pjoshea13 in reply to eggraj8]

Patrick Walsh at Hopkins reported ~20 years ago that T rises after prostatectomy.

Two other institutions reported the same. All 3 measured T before RP & one year later. The conclusion was that PCa is able to negatively influence T production.

That in itself seems reason enough to replace T.

-Patrick