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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Prostate Cancer Metastatic
• Intervention / Treatment: Diagnostic test: Testosterone levels

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.

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

• Study Contact: Name: Ignacio Puche Sanz; Phone Number: 0034 958 023 158; Email: naho.puchesanz@gmail.com
• Study Contact Backup: Name: Soraya Santana; Phone Number: 0034 958 023 158; Email: ssantana@fibao.es

Study Locations

• Spain
  • Seville, Spain
    • Hospital Universitario Virgen del Rocío
  • Andalucía
    • Córdoba, Andalucía, Spain
      • Hospital Universitario Reina Sofia
    • Granada, Andalucía, Spain
      • Hospital Universitario Virgen de Las Nieves

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• 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).

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early treatment failure	Proportion of patients with PSA progression or death from PCa within 12 months after initiation of treatment.	1 year
PSA response	Lowest PSA (nadir) reached after initiation of treatment	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Testosterone response.	%percent of decrease in testosterone levels at the moment of PSA nadir.	6 months
Biochemical progression-free survival (bPFS)	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.	1 year
Radiologic progression-free survival (rPFS)	Assessed by PCWG3 progression criteria on nodal, visceral and bone disease.	1 year
Time to CRPC	Time (months) from treatment initiation to the development of a CRPC status.	1 year

Collaborators and Investigators

• Sponsor: Ignacio Puche Sanz
• Collaborators: Chinese University of Hong Kong; UMC Utrecht; University of Padova; Medical University Innsbruck; Azienda Ospedaliera San Giovanni Battista; Hospital Universitario Reina Sofia de Cordoba; Hospitales Universitarios Virgen del Rocío; Hospital San Carlos, Madrid; San Raffaele University Hospital, Italy; Institut Mutualiste Montsouris; Hospital Universitario Torrecárdenas; Hospital Neurotraumatologico de Jaen
• Investigators: Principal Investigator: Ignacio Puche, Fundación para la Investigación Biosanitaria de Andalucía Oriental (FIBAO)

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2023
• Primary Completion (Anticipated): January 1, 2025
• Study Completion (Anticipated): January 1, 2026

Study Registration Dates

• First Submitted: September 2, 2022
• First Submitted That Met QC Criteria: September 2, 2022
• First Posted (Actual): September 7, 2022

Study Record Updates

• Last Update Posted (Actual): September 14, 2022
• Last Update Submitted That Met QC Criteria: September 9, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Testosterone, biomarker
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Androgens; Testosterone
• Other Study ID Numbers: BATEMARK-YAUPCa-21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No