Clinical trial NCT05530395: BAseLine TEstosterone as a Prognostic and/or Predictive bioMARKer in mHSPC
Official title: Baseline Testosterone as a Prognostic and/or Predictive Biomarker in Metastatic Hormone Sensitive Prostate Cancer
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Prostate Cancer Metastatic
Keywords: Testosterone, biomarker
Lead sponsor: University Hospital Virgen de las Nieves
Sponsor class: OTHER
Collaborators: name: Hospital Universitario Reina Sofia de Cordoba
name: Hospitales Universitarios Virgen del Rocío
name: Hospital Universitario Torrecárdenas
name: Hospital Neurotraumatologico de Jaen
name: Hospital San Carlos, Madrid
name: Institut Mutualiste Montsouris
name: San Raffaele University Hospital, Italy
name: Azienda Ospedaliera San Giovanni Battista
name: Chinese University of Hong Kong
name: Medical University Innsbruck
name: University of Padova
name: UMC Utrecht
First posted: 2022-09-07
Enrollment: 300
Sex: MALE
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Metastatic hormone sensitive prostate cancer (mHSPC) patients diagnosed by any imaging test (at least CT and/or bone scan).

Brief summary: 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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Metastatic hormone sensitive prostate cancer (mHSPC) patients diagnosed by any imaging test (at least CT and bone scan) including:

  * Any newly diagnosed mHSPC with no prior treatments.
  * Primarily treated PCa that have progressed to mHSPC with no prior ADT in the last 2 years.
  * Patients receiving ADT + EBRT as primary treatment will also be included.
* Patients who agree to be followed prospectively according to routine clinical practice in the context of this study.

Exclusion Criteria:

* Any prior androgen deprivation therapy (ADT) scheme 2 years before recruitment. - Any prior testosterone replacement therapy scheme 2 years before recruitment.
* Previous intermittent ADT schemes.
* Prior testicular excision surgery.
* Absence or testicular atrophy from any cause.
* Whenever further prospective clinical follow-up is not possible or patient do not accept follow-up in the context of this study.

Primary outcomes:
measure: Early treatment failure
timeFrame: 1 year
measure: PSA response
timeFrame: 6 months
Secondary outcomes:
measure: Testosterone response.
timeFrame: 6 months
measure: Biochemical progression-free survival (bPFS)
timeFrame: 1 year
measure: Radiologic progression-free survival (rPFS)
timeFrame: 1 year
measure: Time to CRPC
timeFrame: 1 year
Other outcomes:
Locations:
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
state: Andalucía
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
state: Andalucía
city: Seville
country: Spain
facility: Hospital Universitario Virgen del Rocio
Study officials:
affiliation: Fundación para la Investigación Biosanitaria de Andalucía Oriental (FIBAO)
name: Ignacio Puche
role: PRINCIPAL_INVESTIGATOR
References:
citation: Michaud JE, Billups KL, Partin AW. Testosterone and prostate cancer: an evidence-based review of pathogenesis and oncologic risk. Ther Adv Urol. 2015 Dec;7(6):378-87. doi: 10.1177/1756287215597633.
citation: Pierorazio PM, Ferrucci L, Kettermann A, Longo DL, Metter EJ, Carter HB. Serum testosterone is associated with aggressive prostate cancer in older men: results from the Baltimore Longitudinal Study of Aging. BJU Int. 2010 Mar;105(6):824-9. doi: 10.1111/j.1464-410X.2009.08853.x. Epub 2009 Sep 14.
citation: Yano M, Imamoto T, Suzuki H, Fukasawa S, Kojima S, Komiya A, Naya Y, Ichikawa T. The clinical potential of pretreatment serum testosterone level to improve the efficiency of prostate cancer screening. Eur Urol. 2007 Feb;51(2):375-80. doi: 10.1016/j.eururo.2006.08.047. Epub 2006 Sep 12.
citation: Rajek NJ. Developing an evening clinical experience for baccalaureate community health nursing students. J Nurs Educ. 1987 May;26(5):197-200. doi: 10.3928/0148-4834-19870501-07.