(UroToday.com) The 2025 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA was host to the Case-Based Session: Management of Biochemical Recurrence After Radiation Therapy for Localized Prostate Cancer. Dr. Alicia Morgans discussed the Impact of Salvage Therapies: Functional Outcomes and Quality of Life
Dr. Morgans began her presentation by emphasizing that quality of life (QOL) considerations should be a standard component of all treatment-related decisions and should be non-negotiable.
QOL encompasses patient-reported outcomes (PROs), health-related quality of life (HRQOL), fatigue, pain, symptoms, function, and treatment satisfaction—factors that influence medication adherence. Additionally, the "X factor," often underrecognized in clinical trials, includes burdens on family, ability to work, and time spent at hospital and clinic visits. Efforts should focus on mitigating these challenges in clinical trials to improve patient experience and adherence.
Patient-reported outcome measures (PROMs) are standardized, validated tools that quantify qualitative data, allowing for comparisons between groups and translating subjective experiences into measurable outcomes. Prostate cancer-specific questionnaires include FACT-P, EORTC-PR25, EPIC-26, and PROSQOLI. General measures assess various aspects of well-being, such as depression/anxiety (PHQ-9, HADS), overall QOL (SF-36, EQ-5D, FACT-G), and advanced cancer QOL (EORTC QLQ-C30).
When considering systemic therapy in this scenario, trials like PRESTO provide insight. In PRO data, the QOL outcome curves largely overlap between intermittent and continuous systemic therapy, suggesting similar patient-reported experiences. However, since all patients in these analyses have suppressed testosterone, these findings are not particularly surprising.1
We are not necessarily capturing these factors with high accuracy. Dr. Morgans then discussed the EMBARK trial, highlighting that testosterone levels were elevated with enzalutamide monotherapy but decreased with ADT ± enzalutamide, as shown in the data below.2
Notably, the sexual domain was the only domain that showed a difference compared to the other groups favouring enzalutamide monotherapy. When examining the hormonal and other domains, the curves appear to overlap. This raises an important question: Why is there so little difference in QOL despite such a significant difference in testosterone levels? This is something many of us struggle to understand in clinical practice Dr. Morgans mentioned.
She then discussed the PR-7 study, which evaluated intermittent androgen deprivation therapy (IADT). Patient-reported QOL was superior for hot flashes (P<0.001), desire for sexual activity (P<0.001), and urinary symptoms (P=0.006) with IADT. There was no significant difference in fatigue, or in physical or global health. Notably, 35% of patients recovered to baseline testosterone levels, and 79% achieved testosterone ≥144 ng/dL, which was required at eligibility. However, fewer and fewer patients experienced a treatment-off period over time, and fewer had testosterone recovery. While IADT showed benefits in some QOL domains, overall global health and fatigue remained similar between groups.3
She posed the critical question: Are we measuring what matters? Systemic therapy trials often suggest minimal differences in QOL between treatment approaches when testosterone is suppressed. While testosterone recovery is sometimes associated with improved QOL, other times it is not. This raises the need for a deeper understanding of how to better capture an individual’s lived experience. Efforts are underway to develop new PROMs that more accurately reflect patient priorities, but more work is needed in this area to ensure we are measuring what truly impacts patient well-being.
Future research efforts, such as the INDICATE study, aim to address some of the unanswered questions in this field. This ECOG-led trial utilizes PSMA PET to guide treatment intensity with SBRT, potentially refining treatment strategies for patients. The results, expected in the coming years, may provide valuable insights into optimizing prostate cancer management based on advanced imaging techniques.
Dr. Morgans discussed two additional trials aimed at avoiding ADT/castration in PSMA PET+ BCR. The first, PSMA DC, randomizes patients to ¹⁷⁷Lu-PSMA-617 or SBRT, while the NRG PROMETHEAN study randomizes patients to SBRT with or without Relugolix. These trials seek to refine treatment strategies for patients with biochemically recurrent prostate cancer, potentially reducing the need for systemic hormonal therapy.
Other trials in progress are the ARASTEP and PRIMORDIUM both evaluating ARPIs early in this setting of BCR.
Dr. Morgans concluded her presentation with the following key messages:
- Quality of Life considerations should be standard components of all treatment-related decisions.
- Patient reported QOL in existing trials suggests that systemic therapy has mild to moderate impact, but we may not be measuring what matters.
- Trials that reduce exposure or avoid castration may eventually provide an opportunity to maximize QOL and maintain disease control.
- Asking patients about QOL and offering interventions to address complaints is a critical and achievable first step in improving QOL.
Presented by: Alicia K. Morgans, MD, MPH, FASCO, Medical Oncologist at the Dana-Farber Cancer Institute, Boston, MA.
Written by: Julian Chavarriaga, MD – Urologic Oncologist at Cancer Treatment and Research Center (CTIC) via Society of Urologic Oncology (SUO) Fellow at The University of Toronto. @chavarriagaj on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025.
References:- Rahul Aggarwal et al, PRESTO: A Phase III, Open-Label Study of Intensification of Androgen Blockade in Patients With High-Risk Biochemically Relapsed Castration-Sensitive Prostate Cancer (AFT-19). JCO 42, 1114-1123(2024) DOI:10.1200/JCO.23.01157
- Freedland SJ, de Almeida Luz M, De Giorgi U, Gleave M, Gotto GT, Pieczonka CM, Haas GP, Kim CS, Ramirez-Backhaus M, Rannikko A, Tarazi J, Sridharan S, Sugg J, Tang Y, Tutrone RF Jr, Venugopal B, Villers A, Woo HH, Zohren F, Shore ND; EMBARK Study. Improved Outcomes with Enzalutamide in Biochemically Recurrent Prostate Cancer. N Engl J Med. 2023 Oct 19;389(16):1453-1465. doi: 10.1056/NEJMoa2303974. PMID: 37851874.
- Crook JM, O'Callaghan CJ, Duncan G, Dearnaley DP, Higano CS, Horwitz EM, Frymire E, Malone S, Chin J, Nabid A, Warde P, Corbett T, Angyalfi S, Goldenberg SL, Gospodarowicz MK, Saad F, Logue JP, Hall E, Schellhammer PF, Ding K, Klotz L. Intermittent androgen suppression for rising PSA level after radiotherapy. N Engl J Med. 2012 Sep 6;367(10):895-903. doi: 10.1056/NEJMoa1201546. Erratum in: N Engl J Med. 2012 Dec 6;367(23):2262. PMID: 22931259; PMCID: PMC3521033.