The 2024 European Society for Medical Oncology (ESMO) and American Society for Radiation Oncology (ASTRO) meetings featured significant updates in the treatment of prostate and bladder cancers, ranging from novel hormonal therapies to advanced radiotherapy techniques.
Transdermal Estradiol as an Alternative to LHRH Analogs
Ursula Vogl highlighted the PATCH trial, a phase III study combined with a STAMPEDE arm, which evaluated transdermal estradiol versus LHRH analogs in non-metastatic prostate cancer. The trial demonstrated non-inferiority in metastasis-free survival (MFS) with transdermal estradiol, showing a three-year MFS of 87% in both arms. Transdermal estradiol also resulted in fewer hot flashes, although it was associated with a higher incidence of gynecomastia (43%). This offers a potential alternative for patients concerned about the metabolic side effects of LHRH analogs.
Darolutamide in Metastatic Hormone-Sensitive Prostate Cancer
The ARANOTE trial, a phase III study, investigated the addition of darolutamide to androgen deprivation therapy (ADT) in metastatic hormone-sensitive prostate cancer (mHSPC). The trial met its primary endpoint of radiographic progression-free survival (rPFS), with a hazard ratio of 0.5 favoring the darolutamide arm. While overall survival data are still immature, the combination showed a favorable trend. Notably, darolutamide was well-tolerated, with adverse events similar to placebo plus ADT, though bone fractures were more frequent.
Metformin's Metabolic Benefits in Prostate Cancer
The STAMPEDE trial also explored the role of metformin in prostate cancer treatment. Although metformin did not improve overall survival as a primary endpoint, subgroup analysis suggested a potential benefit in high-volume disease. Metformin significantly improved metabolic parameters, reducing weight gain, cholesterol, and glucose levels, suggesting a role in mitigating metabolic adverse events associated with hormonal treatments.
PEACE-3 Trial: Radium-223 Plus Enzalutamide in mCRPC
The PEACE-3 trial evaluated the combination of Radium-223 and enzalutamide in metastatic castration-resistant prostate cancer (mCRPC). The study met its primary endpoint of rPFS, with overall survival data pending further follow-up. The combination was generally well-tolerated, although increased rates of anemia and neutropenia were observed. This suggests a potential new standard of care for first-line mCRPC patients with predominant bone metastasis.
Radioligand Therapy with Lutetium PSMA-I&T
The SPLASH trial presented data on lutetium PSMA-I&T in mCRPC, demonstrating a reduction in the risk of rPFS or death by 29% compared to a second androgen receptor pathway inhibitor (ARPI). While overall survival data are immature, the therapy was well-tolerated. However, logistical and regulatory hurdles may limit its widespread implementation.
Radiotherapy Innovations in GU Malignancies
ASTRO 2024 featured discussions on the evolving role of radiotherapy in genitourinary (GU) malignancies. Phuoc Tran discussed the "space-time continuum" in metastatic castration-sensitive prostate cancer (mCSPC), emphasizing the impact of metastatic burden and timing on treatment outcomes. Brandon Mahal highlighted the use of MRI-defined microboost to enhance precision in prostate radiation therapy, improving biochemical disease-free survival. Savita Dandapani presented initial results from the SHARP Phase 2 trial, evaluating stereotactic body radiation therapy, androgen deprivation therapy, and Radium-223 in oligometastatic castrate-sensitive prostate cancer, showing a median progression-free survival of 21.7 months.
Bladder Cancer: Personalized Radiotherapy and Novel Therapeutics
Leslie Ballas emphasized bladder preservation as a modern treatment choice for muscle-invasive bladder cancer, using trimodality therapy. Ananya Choudhury discussed the need for personalized radiotherapy in bladder cancer, highlighting the RAIDER study's findings on adaptive radiotherapy and hypofractionation. Gopakumar Iyer presented on integrating novel therapeutics, like immune checkpoint inhibitors and antibody-drug conjugates, with trimodal therapy for muscle-invasive bladder cancer, citing ongoing clinical trials like Keynote 992 and SWOG S1806. Vedang Murthy presented results from the phase III Bladder Adjuvant RadioTherapy (BART) trial, evaluating the safety of post-cystectomy radiotherapy in high-risk bladder cancer patients, showing reduced locoregional recurrence but increased acute toxicity.
