CUA 2018: Serum Sex Steroids as Prognostic Biomarkers in Patients Receiving ADT for Recurrent Prostate Cancer Post-Radiotherapy: A Post-Hoc Analysis of the PR.7 Trial

Halifax, Nova Scotia ( Toren Paul, MD gave a presentation on a study examining serum sex steroids as prognostic biomarkers in patients receiving androgen deprivation therapy (ADT) for recurrent prostate cancer (PC) after radiotherapy. 

Predictive and prognostic biomarkers for PC patients starting ADT can assist in personalizing treatment. There is a shift in recent years toward earlier treatment and combination treatment for recurrent and metastatic PC. Serum sex steroids possess characteristics of good biomarkers:
  • Accessible
  • Reliable and reproducible
  • Affordable
  • There is biologic plausibility
Nadir testosterone levels within the first year of ADT initiation predict the development of castration resistance and PC mortality. The biologic explanation for these findings is unclear. The objective of this study was to evaluate the prognostic role of serum sex steroids on the development of castration resistance in patients receiving continuous ADT following biochemical recurrence post-radiotherapy. The primary outcome was time to castration resistance, and secondary outcomes included cancer-specific survival (CSS), and overall survival (OS).

A total of 1386 patients were initially enrolled, as can be seen in figure 1.

Figure 1 – Trial consort diagram:
UroToday CUA 2018 Serum Sex Steroids as Prognostic Biomarkers in Patients Receiving ADT 1

The serum of the patients was cryopreserved for Gas chromatography-mass spectrometry (GC-MS) analysis. The sex steroids that were analyzed with their lower limit of quantification (LLOQ) are demonstrated in table 1 and figure 2.

Table 1 – Sex steroids analyzed in this study:
UroToday CUA 2018 Serum Sex Steroids as Prognostic Biomarkers in Patients Receiving ADT 2

Figure 2 – The sex steroids that were analyzed:
UroToday CUA 2018 Serum Sex Steroids as Prognostic Biomarkers in Patients Receiving ADT 3

Patient characteristics are demonstrated in table 2. The median follow-up was ~7 years.

The results showed that increasing age was associated with decreasing sex steroid values. There was also high intra-patient correlation among all steroids, except progesterone and 3 beta-diol, where values commonly fell below the LLOQ. Estrone (E1) and estradiol (E2) levels were shown to significantly predict time to CRPC. Furthermore, rising adrenal androgen (DHEA and androsterone) levels also were shown to predict time to CRPC. 

The overall levels of circulating sex steroids levels appear to impact the time to castration resistance. The increase of DHEA and androsterone implicated in ‘backdoor’ androgen synthesis pathway may signal a particular resistance phenotype. This is the first study to indicate that estrone and estradiol serum levels following ADT initiation have long-term prognostic value. Further research is needed to understand how sex steroids impact the intraluminal biology of castration resistance and how these prognostic biomarkers can help us personalize therapy. Unfortunately, sex steroids were not measured prior to ADT initiation, so baseline data was unavailable.

Table 2 – Patient characteristics:
UroToday CUA 2018 Serum Sex Steroids as Prognostic Biomarkers in Patients Receiving ADT 4
Toren summarized his talk by emphasizing that higher estrone, estradiol and serum androgens (DHEA and androsterone) levels following ADT are associated with faster time to castration resistance. These findings require validation before use of these biomarkers to personalize treatment for men initiating ADT.

Presented by: Toren Paul, MD, Department of Surgery, Division of Urology, Université Laval, Quebec, QC, Canada

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, @GoldbergHanan at the 73rd Canadian Urological Association Annual Meeting - June 23 - 26, 2018 - Halifax, Nova Scotia

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