📬 GU Oncology Intelligence Digest — Week 2026-W37

KEYNOTE-564 five-year data show an overall survival benefit for adjuvant pembrolizumab in ccRCC, the 2026 AUA and EAU NMIBC guidelines reclassify high-grade Ta as high-risk and add checkpoint inhibitors to BCG, RADICAL PC-2 finds cardiology referral for men on ADT lowers cholesterol but not cardiovascular events, and a Korean phase 3 shows 26-fraction salvage prostate bed radiotherapy matches 33 fractions.

⚡ TL;DR

🐦 Twitter / 🦋 Bluesky

RADICAL PC-2 at ESC 2026: cardiology referral for men starting ADT lowered cholesterol but not cardiovascular events — In 2,487 men with prostate cancer starting ADT across 55 sites randomized to usual care versus routine cardiology/internist referral with statin for all, cholesterol was lower in the treatment group but the composite of CV death, MI, stroke and heart failure showed sHR 1.08 (0.79 to 1.49) over median follow-up of 5.8 years
Update: KEYNOTE-564 five-year results published in Annals of Oncology turn the adjuvant pembrolizumab DFS benefit into a mature overall survival benefit — At a median follow-up of about 70 months, 5-year DFS was 60.9% vs 52.2% (HR 0.71, 95% CI 0.59-0.86) and 5-year OS 87.7% vs 82.3% (HR 0.66, 95% CI 0.48-0.90) in 994 patients randomized after nephrectomy
FDA approval of durvalumab plus BCG for BCG-naive high-risk NMIBC based on POTOMAC brings medical oncologists into non-muscle-invasive disease — POTOMAC was a phase III trial of BCG plus durvalumab versus BCG alone in BCG-naive high-risk NMIBC, with DFS HR 0.68 and 3-year median DFS 82% vs 77%
FDA approval of belzutifan plus pembrolizumab in adjuvant RCC on LITESPARK-022 arrives with a large grade ≥3 toxicity gap — LITESPARK-022 reported 2.5-year DFS 75.8% vs 68.6% (HR 0.72) and 2.5-year OS 95.6% vs 93.8% (HR 0.78) versus pembrolizumab alone, with grade ≥3 adverse events 42.2% vs 17.9%
Korean phase 3 in JCO: 26-fraction moderately hypofractionated salvage radiotherapy after prostatectomy matches 33 fractions — In 316 patients with biochemical recurrence after radical prostatectomy and median pre-RT PSA 0.36, 65 Gy/26 fx versus 66 Gy/33 fx gave 4-year bPFS 80.1% vs 78.1%, DMFS 91.7% vs 91.0% and CSS 100% in both arms at median follow-up 52.6 months

Full details below ↓

📄 What's Being Published

Manuscripts:

Darolutamide-based triplet therapy versus androgen receptor pathway inhibitor-based doublet therapy for metastatic castration-sensitive prostate cancer: a real-world analysis using the TriNetX database. — Tohi Yoichiro et al., Jpn J Clin Oncol

Among 1,841 patients with mCSPC meeting eligibility criteria from TriNetX data spanning August 2018 to July 2026, after 1:1 propensity score matching (n = 329), triplet therapy was associated with a statistically significant improvement in OS compared with doublet therapy (HR 0.601; 95% CI 0.420–0.862; log-rank P = .005). Depth of PSA response also favoured triplet therapy: PSA ≤0.2 ng/ml was achieved by 26.4% vs 17.0% at 3 months (P = .003) and 50.5% vs 40.1% at any time (P = .008).

Clinical bottom line: This real-world TriNetX comparison continues to favour a darolutamide-docetaxel triplet over ARPI doublets for metastatic castration-sensitive prostate cancer on both overall survival and depth of PSA response; the absence of any head-to-head ARPI doublet trial means the doublet choice itself remains unsettled.

Read full article →

🗂 Every paper considered this week, including the ones that didn’t make it →

🗣️ What People Were Discussing This Week

How these are chosen: filtered for clinical relevance, grouped by the new development discussed, then ordered by engagement (bookmarks and reposts).

RADICAL PC-2 at ESC 2026: cardiology referral for men starting ADT lowered cholesterol but not cardiovascular events

RADICAL PC-2 enrolled 2,487 men with prostate cancer starting ADT across 55 sites and randomized them to usual care versus routine cardiology or internist referral with a statin for all, with a median follow-up of 5.8 years. Cholesterol was lower in the referral group, but the composite of CV death, MI, stroke, and heart failure showed sHR 1.08 (0.79 to 1.49) — no difference between arms. Routine referral improved cholesterol control and overall risk factor management without translating into a reduction in major cardiovascular events. The practical question the data leave open is whether the lesson is to skip the cardiology referral and simply start the statin on day 1 of ADT.

Discussed by: @avirupguha, @jgong15, @JAMAInternalMed

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Update: KEYNOTE-564 five-year results published in Annals of Oncology turn the adjuvant pembrolizumab DFS benefit into a mature overall survival benefit

The five-year follow-up of KEYNOTE-564, now published in Annals of Oncology, reports data from 994 patients randomized after nephrectomy ± metastasectomy to approximately one year of pembrolizumab versus placebo. At a median follow-up of approximately 70 months, 5-year DFS was 60.9% vs 52.2% (HR 0.71, 95% CI 0.59–0.86) and 5-year OS was 87.7% vs 82.3% (HR 0.66, 95% CI 0.48–0.90); a separate long-term summary also cites 6-year DFS of 58.5% vs 48.7% (HR 0.71). Described as the first adjuvant trial in kidney cancer to demonstrate a survival benefit at five or more years, this is now characterised as a sustained overall-survival advantage extending years after a finite treatment course ends — not simply a DFS-positive result. With that maturity, the debate shifts to whether any high-risk resected ccRCC patient exists for whom adjuvant pembrolizumab would not be discussed.

Discussed by: @EladSharonMD, @ChandrakanthMv, @OncoAlert, @OncoAlert, @ulvyeoflas

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FDA approval of durvalumab plus BCG for BCG-naive high-risk NMIBC based on POTOMAC brings medical oncologists into non-muscle-invasive disease

The FDA has approved durvalumab plus BCG for BCG-naive high-risk non-muscle-invasive bladder cancer on the basis of POTOMAC, a phase III trial comparing BCG plus durvalumab versus BCG alone. DFS HR was 0.68, with 3-year median DFS 82% vs 77%. Published in The Lancet, the trial is expected to draw medical oncologists into a disease space historically managed exclusively by urologists, with the anticipated model being urologist-administered durvalumab alongside medical oncologist collaboration for immune-related adverse events. The open question is which specialty should own immune toxicity management in this setting.

Discussed by: @OncBrothers, @urotoday

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FDA approval of belzutifan plus pembrolizumab in adjuvant RCC on LITESPARK-022 arrives with a large grade ≥3 toxicity gap

LITESPARK-022, the phase III trial of belzutifan plus pembrolizumab versus pembrolizumab alone in adjuvant RCC, supported a new FDA approval and reported 2.5-year DFS of 75.8% vs 68.6% (HR 0.72) and 2.5-year OS of 95.6% vs 93.8% (HR 0.78), with grade ≥3 adverse events occurring in 42.2% vs 17.9% of patients. Clinicians are grouping LITESPARK-022 alongside PROTEUS and TALAPRO-3 as part of a trend toward earlier treatment intensification in GU oncology. The central tension is whether a 7-point DFS gain justifies more than doubling grade ≥3 toxicity in patients who are already disease-free after nephrectomy.

Discussed by: @OncBrothers, @katy_beckermann

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Korean phase 3 in JCO: 26-fraction moderately hypofractionated salvage radiotherapy after prostatectomy matches 33 fractions

In 316 patients with biochemical recurrence after radical prostatectomy and median pre-RT PSA of 0.36, 65 Gy in 26 fractions versus 66 Gy in 33 fractions to the prostate bed (51% received ADT; 69% had pelvic nodal coverage) produced 4-year bPFS of 80.1% vs 78.1%, DMFS of 91.7% vs 91.0%, and CSS of 100% in both arms at a median follow-up of 52.6 months. Grade 2 or higher GI toxicity was 7.9% vs 0.7%, concentrated in patients without an endorectal balloon, and all events resolved. The URONCOR 06-24 series similarly showed low and comparable early GU/GI toxicity with no meaningful differences in patient-reported outcomes for salvage hypofractionation. The practical question is whether seven fewer trips to the radiotherapy department is sufficient to make moderate hypofractionation the default salvage prescription after prostatectomy.

Discussed by: @JCO_ASCO, @abraocantoMD

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JAMA Network Open mapping of 436 bladder cancer trials finds 77.3% of US counties have none

A geographic mapping of 436 bladder cancer clinical trials across US counties found that among 3,145 US counties, 77.3% had no bladder cancer trials. Trial access was concentrated in less socially vulnerable counties and was less available in counties with higher mortality — a direct mismatch between where trials are located and where disease burden is greatest. The data prompt a concrete question: what structural step would place a bladder cancer trial in the high-mortality, high-vulnerability counties currently excluded from access?

Discussed by: @neerajaiims, @JAMANetworkOpen

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EORTC 2238 DE-ESCALATE design published in European Urology tests intermittent maximal androgen blockade in mHSPC

The EORTC 2238 DE-ESCALATE trial, with its design now published in European Urology, asks whether intermittent maximal androgen blockade can reduce treatment burden while maintaining outcomes in selected men with mHSPC receiving ADT plus ARPI. The parallel OPTIMAS phase 2 randomized trial is separately evaluating treatment de-intensification in metastatic hormone-sensitive prostate cancer. The debate for clinicians centres on which mHSPC patients on ADT plus ARPI would be appropriate candidates for an intermittent-therapy trial and what evidence would be required before pausing treatment outside a protocol.

Discussed by: @BertrandTOMBAL, @urotoday

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FDA approval of EV plus pembrolizumab in cisplatin-ineligible resectable MIBC on KEYNOTE-B15/EV-304, immediately met with an indirect comparison questioning EV's contribution

KEYNOTE-B15/EV-304, the basis for FDA approval of enfortumab vedotin plus pembrolizumab in cisplatin-ineligible resectable muscle-invasive bladder cancer, reported 2-year EFS of 79.4% vs 66.2% (HR 0.53), 2-year OS of 86.9% vs 81.3% (HR 0.65), and pCR of 55.8% vs 32.5%, with rash and neuropathy as the principal adverse events. An indirect comparison of EV-303 and PURE-01 using Guyot graphical reconstruction of Kaplan-Meier curves in cisplatin-ineligible MIBC has since questioned how much enfortumab vedotin is contributing to pembrolizumab efficacy in this setting. The core debate is how much of the perioperative benefit is attributable to enfortumab vedotin beyond pembrolizumab alone.

Discussed by: @OncBrothers, @urotoday

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PEACE-3 ad hoc analysis shows radium-223 added to enzalutamide produces faster and deeper alkaline phosphatase and PSA responses

An exploratory ad hoc analysis of the PEACE-3 trial — published as "Alkaline Phosphatase and Prostate-specific Antigen Response in Metastatic Castration-resistant Prostate Cancer Treated with Enzalutamide Alone or in Combination with Radium-223: Ad Hoc Analysis of the PEACE-3 Consortium Trial" — found that adding radium-223 to enzalutamide in patients with mCRPC and bone metastases produced faster and more frequent biomarker responses than enzalutamide alone. The combination improved alkaline phosphatase responses and normalization and significantly increased deep PSA responses. The question for clinicians is whether these faster and deeper biomarker responses change the threshold for adding a bone-targeted radiopharmaceutical earlier in the treatment course.

Discussed by: @OncoAlert, @vcclibrary.bsky.social

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Spanish national real-world SBRT cohort in oligometastatic disease reports best PFS and OS in prostate cancer patients

A multicentre Spanish real-world study of 300 oligometastatic patients across 12 radiotherapy centres treated between 2020 and 2024 found 1- and 2-year progression-free survival of 45.1% and 36.3%, overall survival of 92% and 82.9%, and local control of 90.5% and 85.5%; severe toxicity was rare. Multivariable analyses showed significantly better PFS and OS in prostate cancer patients. In selected oligometastatic RCC patients, active surveillance or metastasis-directed therapy may offer time off systemic therapy with no survival disadvantage. The unresolved question is whether real-world SBRT data sufficient to buy time off systemic therapy justify metastasis-directed treatment outside a trial in oligometastatic GU cancers.

Discussed by: @OncoAlert, @ChiaraRe

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🔥 Top Ranked Tweets

OncoAlert @OncoAlert

RT @DrRishabhOnco: KEYNOTE-564: the 5-year update strengthens the case for adjuvant pembrolizumab in high-risk ccRCC.

994 patients after nephrectomy ± metastasectomy were randomized to pembrolizumab for ~1 year vs placebo.

At a median follow-up of ~70 months:

• 5-year DFS: 60.9% vs 52.2%
HR 0.71 (95% CI 0.59–0.86)

• 5-year OS: 87.7% vs 82.3%
HR 0.66 (95% CI 0.48–0.90)

• Benefit remained broadly consistent across key subgroups, including risk category, tumor grade and sarcomatoid features.

Safety was unchanged from prior analyses, with no new treatment-related safety signal emerging with longer follow-up.

Why it matters:
The DFS benefit has matured into a sustained OS advantage. This is no longer just recurrence delay.

Clinical verdict: ✅ Practice-changing and practice-confirming.
For appropriately selected patients with resected ccRCC at increased recurrence risk, adjuvant pembrolizumab remains the benchmark standard.

@ASCO @oncoalert
#KidneyCancer #RCC #KEYNOTE564 #Immunotherapy

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