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Highlights from the 2026 ASCO Genitourinary Cancers Symposium
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| ADT and Radiotherapy with or Without Cabazitaxel in Very High-Risk Localized Prostate Cancer: First Results of the PEACE-2 Randomized Phase III Trial
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| Karim Fizazi, MD, PhD
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| Karim Fizazi presented PEACE‑2 which randomized 761 men with very high‑risk localized prostate cancer to ADT + prostate radiotherapy with or without neoadjuvant cabazitaxel (and with or without pelvic RT) and found no improvement in clinical progression‑free survival, biochemical PFS, metastasis‑free survival, or prostate cancer–specific survival with cabazitaxel.
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| External Validation of a Digital Pathology-Based MMAI-Derived Prognostic Biomarker in the Randomized Phase III CHHiP Trial
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| Anna Wilkins
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| In the CHHiP phase III radiotherapy trial, application of the locked ArteraAI MMAI digital pathology model to 1,797 men with localized prostate cancer showed that the MMAI score was strongly associated with both biochemical/clinical recurrence and distant metastases, with high‑risk patients having about a fivefold higher recurrence risk than low‑risk patients. Incorporating MMAI into existing Cambridge Prognostic Group and NCCN risk models significantly improved prognostic discrimination and model fit, supporting its potential use to better personalize treatment intensity in localized prostate cancer.
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| Genomic Alterations and Pathologic Responses to Neoadjuvant ARPI Doublets Versus Docetaxel Triplets in the Genomic Umbrella Neoadjuvant Study (GUNS)
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| Martin Gleave, MD, FRCSC, FACS
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| In the phase 2 GUNS trial, high-risk localized prostate cancers with aggressive genomic alterations had markedly higher minimal residual disease rates with neoadjuvant ARPI + docetaxel triplet therapy than with ARPI doublet alone. ETS fusions were linked to poorer pathologic responses in these biomarker-selected tumors, and ongoing expansion of the docetaxel triplet cohort aims to refine how genomic subtypes should guide intensified neoadjuvant strategies
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| Preliminary Phase 1 Dose Escalation Results of VIR-5500 (AMX-500), a Dual Masked PRO-XTEN T-Cell Engager, in mCRPC
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| Johann De Bono, MD, MSc, PhD, FRCP
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| Preliminary phase 1 data with the dual-masked T‑cell engager VIR‑5500 in heavily pretreated mCRPC show a favorable safety profile with mostly low‑grade CRS, no dose‑limiting toxicities, and a low rate of grade ≥3 treatment‑related events even without prophylactic steroids or anti–IL‑6. At higher Q3W doses, VIR‑5500 induced rapid, deep, and in some cases durable responses, including PSA50/PSA90 declines and a 45% objective response rate in RECIST‑evaluable patients, supporting further development of this PRO‑XTEN platform.
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| HRQoL, Pain, and Symptomatic Skeletal Events in the Phase 3 PSMAddition Study of 177Lu-PSMA-617 Combined with ADT and ARPI in Patients with PSMA-Positive mHSPC
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| Michael Morris, MD
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| In PSMAddition, adding 177Lu‑PSMA‑617 to ADT plus an ARPI in PSMA‑positive mHSPC improved radiographic PFS without compromising patient experience. Health-related quality of life, pain scores, and time to symptomatic skeletal events were broadly similar between arms over roughly two years of follow-up, suggesting that the radioligand therapy can deepen disease control while maintaining day‑to‑day functioning.
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| First-in-Human Assessment of 225Ac-PSMA-Trillium (BAY 3563254) in mCRPC: Dose-Escalation Results of the Phase 1 PAnTHA Study
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| Fred Saad, CQ, MD, FRCS, FCAHS
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| In the phase 1 PAnTHA trial, first‑in‑human 225Ac‑PSMA‑Trillium showed a favorable safety profile in mCRPC, with no dose‑limiting toxicities, no grade 3 xerostomia, and primarily low‑grade dry mouth as the main side effect. At the selected expansion dose of 125 kBq/kg, antitumor activity was striking, with high PSA response rates and substantial objective responses—especially in patients with high PSMA PET uptake—supporting ongoing dose‑expansion cohorts to define its role across post‑ and pre‑chemotherapy settings and after 177Lu‑PSMA‑617.
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| Real-World Outcomes of Radium-223 in the FRONTIER Study: Impact of Prior Up-Front Therapy in mCRPC
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| Takuma Kato, MD, PhD
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| The FRONTIER study, presented by Dr. Takuma Kato at ASCO GU 2026, examined real-world outcomes of radium-223 in 802 Japanese mCRPC patients, comparing those with prior upfront intensified therapy during the hormone-sensitive phase to those on vintage hormonal therapy. After propensity score matching, radium-223 showed comparable six-cycle completion rates, progression times, overall survival, and safety profiles, regardless of prior intensification.
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| Real-World Characteristics of Long-Term Survivors with mCRPC Treated with Radium-223: An Analysis of the Global REASSURE Study
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| Saby George, MD, FACP
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| The REASSURE study analysis, presented by Dr. Saby George characterized long-term survivors among 1,472 mCRPC patients with bone metastases, finding 27% achieved this milestone with median OS of 38.1 months versus 10.7 months for others. Long-term survivors had favorable baseline traits like better ECOG status, lower disease burden, and no prior ARPI/taxane therapy, with ≥5 radium-223 doses strongly predicting survival.
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| PAM50 Intrinsic Subtyping and Decipher Genomic Classifier in BCR After Prostatectomy: Implications for ADT Selection
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| Jonathan Tward, MD, PhD, FASTRO
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| This single-institution study of 123 men with biochemical recurrence after prostatectomy found that PAM50 Luminal B tumors had the highest Decipher genomic risk scores and the greatest reduction in metastasis risk when ADT was added to salvage radiotherapy. However, many Non–Luminal B tumors also had high Decipher scores, and no statistically significant interaction between subtype and ADT benefit was detected, suggesting ADT should not be withheld solely based on non–Luminal B status when genomic risk is elevated.
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| Androgen-Receptor Pathway Inhibitors Triplet Therapy (ARAAT): Real-World Outcomes in Metastatic Hormone-Sensitive Prostate Cancer
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| Alicia Morgans, MD, MPH
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| The ARAAT real-world study of 592 mHSPC patients treated with triplet therapy found that darolutamide + ADT + docetaxel was associated with significantly longer time to treatment discontinuation, progression free survival, time to next treatment, and overall survival than abiraterone + ADT + docetaxel after adjustment for baseline factors.
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| Survival Outcomes of Patients with mCRPC Receiving 177Lu-PSMA-617 by Prior Taxane Exposure
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| Micah Ostrowski, MD
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| This Flatiron Health–based retrospective analysis of 850 mCRPC patients treated with 177Lu‑PSMA‑617 after prior ARPI found that the radioligand maintained clinical activity regardless of taxane timing, with median real-world overall survival of 12 months for taxane-before-Lu, 16 months for taxane-after-Lu, and 14 months for taxane-naïve patients.
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| Treatment Utilization Among Patients with mHSPC in Real-World US Settings: A Prostate Cancer Disease Observation (PRECISION) Data Platform Analysis
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| Daniel George, MD
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| Daniel George's analysis from the PRECISION dataset examined treatment patterns in 43,415 US mHSPC patients diagnosed 2020-2025, revealing 39.2% received ADT monotherapy overall, 57.1% doublet therapy, and 3.8% triplet therapy. In the first 4 months post-diagnosis, 49.2% started ADT alone, with 20.4% later intensifying to doublet/triplet; uptake of intensified regimens grew modestly over time but lagged guidelines, especially in community urology versus academic oncology.
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| ctDNA Dynamics in Bone-Dominant mCRPC Treated with Radium-223 with or Without Olaparib: Biomarker Analyses from the Multicenter, Randomized, Phase 2, Investigator-Initiated COMRADE Trial
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| Rana McKay, MD
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| In the phase 2 COMRADE trial of bone-dominant mCRPC, early on-treatment ctDNA dynamics at cycle 2 day 1 were prognostic: patients with undetectable ctDNA or ≥50% tumor-fraction decline had markedly longer radiographic progression-free and overall survival than those without molecular response, whereas early PSA changes were not informative.
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| Comparison of Docetaxel Triplet Therapy with ARPI Doublet in US Veterans with mHSPC
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| Abigail Chu, BS
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| In this real-world VA cohort of 608 propensity-matched men with mHSPC, docetaxel triplet therapy was associated with significantly lower mortality than ARPI doublet therapy, with median overall survival not yet reached in either group. The survival advantage was concentrated in patients with synchronous, high-volume disease, while no clear benefit emerged in metachronous or low-volume cases; an exploratory analysis suggested darolutamide-based triplets may outperform abiraterone-based triplets but requires prospective validation.
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| Development and Validation of CHAI-Powered Prognostic and Predictive Biomarkers in mHSPC Using ENZAMET and CHAARTED Prospective Randomized Phase 3 Trials
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| Neeraj Agarwal, MD, FASCO
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| This analysis used a deep learning histology platform on H&E slides from ENZAMET, CHAARTED, and real-world cohorts to develop three biomarkers in mHSPC: a prognostic score and two predictive scores for docetaxel and ARPI benefit. All three were externally validated in phase 3 trials, where ProgPC independently stratified survival risk and PredDoce/PredARPI showed significant treatment–biomarker interactions for both PFS and OS, suggesting they could help personalize when to escalate to triplet or ARPI-based therapy in mHSPC.
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| Phase 2 Expansion Study of 212Pb-ADVC001 in Metastatic Prostate Cancer: The TheraPb Trial
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| Aaron Hansen, MD
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| The TheraPb phase 2 expansion study is evaluating 212Pb‑ADVC001, an alpha‑emitting PSMA‑targeted radioligand, in three metastatic prostate cancer settings: suboptimally responding mHSPC, 177Lu‑PSMA–naïve mCRPC, and mCRPC previously treated with 177Lu‑PSMA. Patients are randomized to 160 or 200 MBq every cycle for up to 4 induction and as many as 12 total adaptive doses, with efficacy assessed by PSA, conventional imaging, and PSMA PET/CT plus detailed safety, dosimetry, and biomarker analyses over up to 5 years of follow‑up.
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| OPTIMAS: A Phase II Randomized, Decentralized, De-Escalation Trial in Patients with mHSPC Achieving Optimal PSA Response
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| Umang Swami, MD, MS
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| OPTIMAS is a phase II, randomized, de-escalation trial testing whether men with mHSPC who achieve an optimal PSA response on relugolix + ARPI can safely switch to intermittent therapy instead of continuing continuous treatment. Cohort A randomizes optimal responders to intermittent versus continuous relugolix + ARPI with fatigue and quality-of-life as primary/secondary outcomes, while Cohort B is a single-arm intermittent cohort focused on 1‑year progression-free survival, aiming to reduce treatment toxicity without compromising disease control in this biologically selected population.
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| Dose Optimization and PSMA Receptor Intensification with 177Lu-PSMA-597 in mCRPC: The Randomized Phase II OPTIMAL-PSMA Trial
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| Louise Emmett, BSc(HONS), MBChB, FRACP, FAANMS, MD
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| Louise Emmett presented on the OPTIMAL-PSMA is a randomized phase II trial in mCRPC testing whether an intensified induction schedule of 177Lu‑PSMA‑597 (three doses over 15 days followed by 10‑weekly maintenance) can safely improve PSA50 response and other outcomes compared with standard 6‑weekly dosing.
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