Prostate cancer at ASCO 2026: Which late-breakers could change practice?

PROTEUS

→ Abstract LBA1: Taplin ME, Gleave M, Shore ND, et al. Perioperative (neoadjuvant and adjuvant) apalutamide (APA) + androgen deprivation therapy (ADT) vs placebo (PBO) + ADT with radical prostatectomy (RP) in high-risk localized or locally advanced prostate cancer (HR LPC/LAPC): Final analysis of the PROTEUS phase 3 study. Presented at: ASCO, Chicago, IL, USA. May 29 to June 2, 2026

The phase 3 PROTEUS trial (NCT03767244) randomized 2,109 patients with high-risk localized or locally advanced prostate cancer to perioperative apalutamide plus androgen deprivation therapy (ADT) or placebo plus ADT with radical prostatectomy. After a median follow-up of 61.7 months, both primary endpoints were met. The pCR/MRD rate was 8.9% versus 1.0% (OR 10.17; 95% CI 5.27-19.64; p<0.0001). Metastasis-free survival was significantly improved with HR 0.80 (95% CI 0.67-0.96; p=0.0169), with 5-year MFS rates of 78.2% versus 73.5%. Grade 3/4 adverse events occurred in 39.6% versus 31.0%. The data support perioperative apalutamide plus ADT as a potential new standard for high-risk localized disease.

Key clinical takeaways
PROTEUS provides phase 3 evidence supporting perioperative androgen receptor pathway intensification in high-risk localized disease. The absolute improvement in 5-year MFS was modest but statistically significant, and the higher pCR/MRD rates suggest enhanced disease control before and after surgery. Toxicity was increased, and the balance between efficacy and treatment burden will need consideration in routine practice. Longer-term overall survival data and patient selection strategies will be important in determining how broadly this approach is adopted.

TALAPRO-3

→ Abstract LBA5007: Agarwal N, Matsubara N, Azad A, et al. TALAPRO-3: Talazoparib (TALA) + enzalutamide (ENZA) compared with placebo (PBO) + ENZA for the treatment of patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) harboring homologous recombination repair (HRR) gene alterations. Presented at: ASCO, Chicago, IL, USA. May 29 to June 2, 2026.

The phase 3 TALAPRO-3 trial (NCT04821622) randomized 599 patients with homologous recombination repair (HRR)-altered metastatic castration-sensitive prostate cancer (mCSPC) to talazoparib plus enzalutamide or placebo plus enzalutamide. At a median follow-up of 37.6 months and 37.7 months, talazoparib significantly improved radiographic progression-free survival (rPFS) (HR, 0.481; 95% CI, 0.357–0.647; 2-sided P<0.0001), with median rPFS not reached versus 45.8 months. Benefit was observed in both BRCA-mutated (HR 0.368; 95% CI, 0.222–0.609) and non-BRCA-mutated (HR 0.567; 95% CI, 0.392–0.819) subgroups. Interim overall survival favored the combination (HR, 0.767; 95% CI, 0.564–1.044) but was not statistically significant.

Key clinical takeaways
TALAPRO-3 extends PARP inhibitor use into the hormone-sensitive setting for biomarker-selected patients. The magnitude of rPFS benefit appears notable, particularly in BRCA-mutated disease, supporting earlier genomic testing in metastatic prostate cancer. However, hematologic toxicity remains substantial, with anemia reported in 71.2% of patients and treatment discontinuation in 18.7%. Overall survival data remain immature, and longer follow-up will clarify whether earlier PARP inhibition translates into durable survival benefit.

COMPPARE 

→ LBA5012: Mendenhall NP, Bryant C, Katz AJ, et al. Early results of COMPPARE, a prospective comparison of outcomes with proton and photon radiation in prostate cancer. Presented at: ASCO, Chicago, IL, USA. May 29 to June 2, 2026

COMPPARE (NCT03561220) is a prospective, non-randomized comparative effectiveness study evaluating proton therapy (PT) versus intensity-modulated radiation therapy (IMRT) in localized prostate cancer. Among 2,524 enrolled patients, 1,404 PT and 939 IMRT patients were included in this analysis. At a median follow-up of 4.0 years, there was no significant difference in the primary endpoint of patient-reported bowel urgency (p=0.324) or bowel frequency (p=0.514) over 2 years. Grade ≥2 gastrointestinal toxicity at 2 years was 5.2% for PT and 5.6% for IMRT (HR 0.91; 95% CI 0.65–1.28; p=0.6). Three-year freedom from biochemical progression was 98.0% versus 97.9% (HR 0.95; 95% CI 0.52–1.71; p=0.90).

Key clinical takeaways
These early findings do not demonstrate a measurable advantage for proton therapy over IMRT in bowel toxicity or short-term disease control. Given the substantial cost differential between modalities, these data may influence payer and institutional decision-making. However, the non-randomized design and relatively early follow-up remain important limitations. Longer-term endpoints, particularly late toxicity and secondary malignancies, may still be relevant in defining any comparative benefit.

ProstACT Global 

→ LBA5009: Barata P, Tincknell G, Gill DM, et al. Safety and dosimetry of ¹⁷⁷Lu-rosopatamab tetraxetan plus SoC in patients with metastatic castration-resistant prostate cancer: Preliminary results from part 1 of phase 3 ProstACT Global study. Presented at: ASCO, Chicago, IL, USA. May 29 to June 2, 2026

Part 1 of the phase 3 ProstACT Global study (NCT06520345) reported preliminary safety and dosimetry findings for ¹⁷⁷Lu-rosopatamab tetraxetan combined with standard of care in 36 patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). Patients received two 76 mCi intravenous doses 14 days apart alongside abiraterone, enzalutamide, or docetaxel. Treatment-emergent adverse events were predominantly hematologic, including thrombocytopenia (77.8%; Grade ≥3 44.4%), neutropenia (63.9%; Grade ≥3 47.2%), and lymphopenia (55.6%; Grade ≥3 41.7%). Xerostomia was limited, with nine Grade 1 events reported. Dosimetry showed highest absorbed radiation in the liver, while lesion activity remained detectable at 15 days.

Key clinical takeaways
These preliminary lead-in data suggest that ¹⁷⁷Lu-rosopatamab can be delivered with expected hematologic toxicity and limited salivary gland toxicity, which remains a relevant consideration for PSMA-targeted radioligands. The dosimetry profile may support further exploration, particularly given prolonged tumor residence and organ exposure below recommended thresholds. However, efficacy outcomes are not yet available, and the small sample size means these findings should primarily be viewed as feasibility and safety data ahead of the randomized component.

This content has been developed independently by Touch Medical Media for touchONCOLOGY. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media. This article was created by the editorial team utilizing AI as an editorial tool (ChatGPT 5.5 [Large language model]. https://chat.openai.com/chat.) The content was developed and edited by human editors. No funding was received in the publication of this article.

Cite: Prostate cancer at ASCO 2026: Which late-breakers could change practice? touchONCOLOGY. 17th June 2026.

Editor: Sophie Nickelson.