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APCCC 2024: Escalation Strategies in Patients with mHSPC and an Unfavourable PSA Decline – Is More Better?

(UroToday.com) The 2024 Advanced Prostate Cancer Consensus Conference (APCCC) meeting featured a session on the management of mHSPC, and a presentation by Dr. Mary-Ellen Taplin discussing escalation strategies in patients with mHSPC and an unfavorable PSA decline. Dr. Taplin started by emphasizing that an unfavorable PSA decline is not equivalent to disease progression. Progression should be based on PSA progression, radiographic progression, and clinical progression. Data from the SWOG 9346 trial of intermittent versus continuous ADT suggests that an unfavorable PSA nadir is prognostic:1

SWOG 9346 trial of intermittent versus continuous ADT
Post-hoc analyses of the CHAARTED data also suggest that a PSA after 7 months of treatment is prognostic for survival among all patients, those receiving ADT alone, or those treated with ADT + docetaxel:2
Post-hoc analyses of the CHAARTED data
Furthermore, Dr. Taplin notes that a PSA nadir is prognostic for AR axis inhibitors in mHSPC:

  • Titan (apalutamide)3
  • LATITUDE (abiraterone)4
  • The STAMPEDE trial arms
  • Various “real world” analyses of apalutamide and a variety of AR-axis inhibitors

A posthoc analysis of the LATITUDE trial showed that PSA kinetics correlated with overall survival and radiographic progression-free survival:5post-hoc analysis of the LATITUDE trial
Dr. Taplin notes that there are several unanswered questions with regard to PSA nadir as a prognostic biomarker:

  1. What time point should we assess? 7 months, or 12 months versus a true nadir?
  2. Is < 0.2 ng/mL the optimal target? Versus 0.02 ng/mL, 0.1 ng/mL, or 0.3 ng/mL
  3. How do genomics factor into the assessment?

Previous work has shown that RB1 alteration is associated with poor survival and that RB1, AR, and TP53 alterations are associated with shorter term on treatment with ARSIs. What should we consider for a patient on therapy for mHSPC who has a suboptimal PSA nadir? Currently, there is no data that exists to change systemic therapy based on PSA nadir, and PSA nadir on therapy can be a randomization point for clinical trials.

Dr. Taplin then provided several clinical considerations:

  • Is the ADT optimal?
    • We need to check testosterone levels
    • If the testosterone level is not castrate, consider measuring in a second lab
    • If the testosterone is measurable, consider assessment of proper injection administration or changing ADT agents and reassessing testosterone decline
  • If on oral therapy, we need to assess if the patient is taking as prescribed
  • If the patient is on an oral AR-axis inhibitor and dose reduced, consider the risk/benefit of increasing to full dose
  • If prostate radiotherapy has not been administered, consider prostate radiotherapy if applicable
  • If the patient was a candidate for stereotactic body radiotherapy to oligo-metastases and did not receive stereotactic body radiotherapy, consider restaging and reconsideration
  • If the patient was a candidate for triplet therapy (especially if synchronous, high volume disease) and is on doublet therapy, consider adding the third therapy, especially if the patient is < 6 months from initiation of therapy
  • If not performed, recommend germ-line testing to prepare for subsequent therapy
  • If not performed, consider somatic sequencing either on the initial biopsy tissue, metastasis biopsy, or liquid test (high likelihood of non-diagnostic if the patient is responding to treatment)
  • Discuss with the patient the concern with suboptimal PSA nadir and strategize on schedule for PSA testing and trigger for imaging restaging – there should be consideration for more frequent monitoring of the patient at risk for early progression

Dr. Taplin concluded her presentation discussing escalation strategies in patients with mHSPC and an unfavourable PSA decline with the following take-home messages:

  • PSA nadir is a prognostic biomarker for radiographic progression free survival and overall survival
  • PSA nadir is not a validated endpoint to change systemic therapy
  • Recognition of suboptimal PSA nadir is an opportunity to evaluate if available standard treatment options are maximized
  • Recognition of suboptimal PSA nadir should prompt careful considerations of future patient assessments

Presented by: Professor Mary-Ellen Taplin, MD, Dana Farber Cancer Institute, Boston, MA

Written by: Zachary Klaassen, MD, MSc - Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 Advanced Prostate Cancer Consensus Conference (APCCC) Meeting, Lugano, Switzerland, Thurs, Apr 25 - Sat, Apr 27, 2024. 

Related content: Escalation Strategies for Suboptimal PSA Decline in mHSPC - Mary-Ellen Taplin

References:

  1. Hussain M, Tangen CM, Higano C, et al. Absolute prostate-specific antigen value after androgen deprivation is a strong independent predictor of overall survival in new metastatic prostate cancer: Data from Southwest Oncology Group Trial 9346 (INT-0162). J Clin Oncol. 2006 Aug 20;24(24):3984-3990.
  2. Harshman LC, Chen YH, Liu G, et al. Seven-month prostate-specific antigen is Prognostic in Metastatic Hormone-Sensitive Prostate Cancer Treated with Androgen Deprivation with or without Docetaxel. J Clin Oncol. 2018 Feb 1;36(4):376-382.
  3. Chi KN, Agarwal N, Bjartell A, et al. Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med 2019 Jul 4;381(1):13-24.
  4. Fizazi K, Tran N, Fein L, et al. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. 2017;377(4):352-360.
  5. Matsubara N, Chi KN, Ozguroglu M, et al. Correlation of Prostate-specific antigen Kinetics with Overall Survival and Radiographic Progression-Free Survival in Metastatic Castration-sensitive Prostate Cancer Treated with Abiraterone Acetate plus Prednisone or Placebo Added to Androgen Deprivation Therapy: Post hoc Analysis of Phase 3 LATITUDE Study. Eur Urol. 2020 Apr;77(4):494-500.