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Blood sample to determine testosterone levels

Testosterone levels

Ignacio Puche Sanz

Soraya Santana

Ignacio Puche

Despite large amounts of basic-science data supporting a role for androgens in PCa pathogenesis, there are conflicting clinical data on the role of endogenous testosterone in human de novo PCa pathogenesis. The investigators hypothesize that lower baseline serum testosterone is significantly associated with worse clinical outcomes in mHSPC patients undergoing continuous medical castration

Biological rationale:

The 'androgen hypothesis' asserts that prostate cancer (PCa) development and progression is driven by androgens. There is significant evidence that androgens promote prostate cancer in experimental models. However, there is no clear evidence that elevations in endogenous testosterone levels promote the development of prostate cancer in humans. Indeed, despite large amounts of basic-science data supporting a role for androgens in PCa pathogenesis, there are conflicting clinical data on the role of endogenous testosterone in human PCa pathogenesis de novo. In reviewing the literature involving PCa development in PCa naive patients, there are studies implicating elevated testosterone, studies implicating lower testosterone, and studies with no association of testosterone and PCa risk.

A recent review in 2015 delved into the controversial role of androgens and prostate cancer and explains the different theories about the ambiguous action of testosterone on the prostate. In 2012, a research proposed the nonlinear U-shaped behaviour or time dependency theory, which postulates that the endocrine biology of the prostate tissue depends on exposure time at a given androgen concentration, which "relies on the fluctuation of the levels of circulating sex steroids during the lifespan of the individual". Another model is the saturation model based on the observations that prostate tissue is extremely sensitive to changes in serum testosterone at low concentrations. This model suggests that there is a nonprotective effect of low testosterone against PCa but tissue becomes indifferent to changes when increasing androgen concentration reach a limit (saturation point), beyond which no further androgen-driven changes are observed. Anyway, the lack of a satisfying model to explain the relationship between androgens and PCa is simply the consequence of insufficient knowledge of the real intrinsic physiopathology of this disease.

Clinical rationale:

Approximately 15% of mHSPC patients primarily fail to respond to ADT. A recent consensus statement on circulating biomarkers for advanced prostate cancer highlighted the urgent need for prospective trials to clinically qualify circulating biomarkers, the greatest need being metastatic PCa. On the other hand, a very recent paper analysed baseline testosterone in hormone-naïve advanced PCa patients undergoing continuous medical castration and selected from 2 large Phase III RCTs. It demonstrated that lower baseline serum testosterone was significantly associated with worse survival end-points and warrants further prospective research in this scenario.

In this era of complex and expensive next-generation markers, this simple, cheap, and well-known biomarker may still have something to say in PCa.

BAseLine TEstosterone as a Prognostic and/or Predictive bioMARKer in mHSPC

Baseline Testosterone as a Prognostic and/or Predictive Biomarker in Metastatic Hormone Sensitive Prostate Cancer

Proportion of patients with PSA progression or death from PCa within 12 months after initiation of treatment.

Lowest PSA (nadir) reached after initiation of treatment

%percent of decrease in testosterone levels at the moment of PSA nadir.

PSA progression: 2 consecutive increase at least 50% or 5 ng/mL or more above PSA nadir on 2 consecutive measurements at least 2 weeks apart.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
BAseLine TEstosterone as a Prognostic and/or Predictive bioMARKer in mHSPC	NCT05530395	Prostate Cancer...	Testosterone le...	18 Years - 89 Years	University Hospital Virgen de las Nieves
BAseLine TEstosterone as a Prognostic and/or Predictive bioMARKer in mHSPC	NCT05530395	Prostate Cancer...	Testosterone le...	18 Years - 89 Years	University Hospital Virgen de las Nieves

Spots Global Cancer Trial Database for testosterone levels