📬 GU Oncology Intelligence Digest — Week 2026-W32

FDA approved Lu-177 PSMA-617 plus ARPI for PSMA-positive mHSPC on PSMAddition, TALAPRO-3 published in NEJM, RADICAL showed radium-223 adds nothing to cabozantinib in bone-metastatic RCC, and BOND-003 Cohort C reported a 75% complete response rate in BCG-unresponsive NMIBC.

⚡ TL;DR

📄 Publications

Intravesical cretostimogene grenadenorepvec oncolytic immunotherapy in high-risk, BCG-unresponsive, non-muscle-invasive bladder cancer with carcinoma in situ (BOND-003 Cohort C): a single-arm, phase 3 trial. — Complete response at any time occurred in 83 (75%) of 110 patients after median follow-up of 25.8 months
Phase II Randomized Trial of Radium-223 Dichloride and Cabozantinib in Patients With Renal Cell Carcinoma With Bone Metastases: RADICAL (Alliance A031801). — Median SSE-free survival was 16.7 vs 17.6 months (sHR 1.46) with cabozantinib plus radium-223 versus cabozantinib

🐦 Twitter / 🦋 Bluesky

Update: KEYNOTE-B15/EV-304 discussion shifts to who does NOT benefit from perioperative EV plus pembrolizumab — 2-year EFS 79.4% vs 66.2% (HR 0.53), OS HR 0.65, pCR 55.8% vs 32.5%, grade >=3 AEs 75.7% vs 67.2%
FDA approves Lu-177 PSMA-617 plus ARPI for PSMA-positive metastatic hormone-sensitive prostate cancer on PSMAddition — Approval was based on PSMAddition with a progression-free survival hazard ratio of 0.72 and immature overall survival
Milan criteria paper argues cystectomy can be spared in selected MIBC patients with clinical complete response — The paper argues cystectomy can be spared in selected MIBC patients with complete response after neoadjuvant therapy
TALAPRO-3 in NEJM: talazoparib plus enzalutamide improves radiographic PFS in HRR-altered metastatic hormone-sensitive prostate cancer — Adding talazoparib to enzalutamide plus ADT reduced risk of progression or death by 52% (HR 0.48), with 3-year rPFS 77% vs 56% and grade >=3 anemia in 51%
Update: LITESPARK-022 FDA approval and quality-of-life debate now centre on whether CTCAE measures what patients feel — Belzutifan plus pembrolizumab was approved with 2.5-year DFS 75.8% vs 68.6% (HR 0.72) and grade >=3 AEs 42.2% vs 17.9%

Full details below ↓

📄 What's Being Published

Manuscripts:

Intravesical cretostimogene grenadenorepvec oncolytic immunotherapy in high-risk, BCG-unresponsive, non-muscle-invasive bladder cancer with carcinoma in situ (BOND-003 Cohort C): a single-arm, phase 3 trial. — Tyson Mark D et al., Lancet Oncol

In BOND-003 Cohort C, after a median follow-up of 25.8 months (IQR 22.1–33.1), complete response at any time was observed in 83 (75% [95% CI 66.3–83.2]) of 110 patients. Treatment-related adverse events occurred in 71 (63%) of 112 patients — most commonly bladder spasm in 28 (25%), pollakiuria in 25 (22%), and micturition urgency in 23 (21%) patients — with no grade 3 or 4 treatment-related adverse events and no treatment-related discontinuations or deaths.

Clinical bottom line: Intravesical cretostimogene delivers a 75% any-time complete response with no grade 3–4 treatment-related toxicity, making it a credible bladder-sparing option for BCG-unresponsive NMIBC with carcinoma in situ.

Read full article →

Phase II Randomized Trial of Radium-223 Dichloride and Cabozantinib in Patients With Renal Cell Carcinoma With Bone Metastases: RADICAL (Alliance A031801). — McKay Rana R et al., J Clin Oncol

In RADICAL, median SSE-free survival for cabozantinib with radium-223 versus cabozantinib alone was 16.7 versus 17.6 months (sHR 1.46 [90% CI 0.86 to 2.51]), median OS was 28.3 versus 19.7 months (sHR 1.40 [95% CI 0.70 to 2.79]), and ORR was 19.4% versus 25.0% (P = .78). The prespecified interim futility analysis was conducted after 90 patients were enrolled and crossed the futility boundary, leading to closure at 98 patients.

Clinical bottom line: Radium-223 should not be added to cabozantinib for bone-metastatic RCC: the combination failed on SSE-free survival, overall survival, and response rate, and the trial closed for futility.

Read full article →

🔗 Also discussed on social media →

Influence of Adverse Pathologic Features on Potential Benefit of Hormone Therapy Use with Postoperative Radiotherapy in Recurrent Prostate Cancer: An Individual Patient Data Meta-analysis. — Kishan Amar U et al., Eur Urol

This meta-analysis included IPD from 4,781 patients with a median follow-up of 9.1 years across five randomized phase 3 trials. Adverse feature count did not significantly modify the OS benefit of hormone therapy (interaction HR 0.93; 95% CI 0.79–1.10; p = 0.4) or the MFS benefit (interaction HR 0.88; 95% CI 0.77–1.01; p = 0.08).

Clinical bottom line: Adverse pathological features are prognostic but not predictive of hormone therapy benefit with postoperative radiotherapy, so they should not be used alone to justify adding hormone therapy at PSA below 0.5 ng/ml.

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Antibody Drug Conjugates in Urothelial Carcinoma: Current Evidence and Practice Considerations. — Salem Samer et al., JCO Oncol Pract

Immune checkpoint inhibitors benefit only approximately 20% of patients in the postplatinum setting. Enfortumab vedotin, targeting Nectin-4, in combination with pembrolizumab has displaced platinum-based chemotherapy as the decades-long standard of care in locally advanced and metastatic disease and has also moved into the perioperative setting for muscle-invasive bladder cancer.

Clinical bottom line: Antibody-drug conjugates have replaced platinum chemotherapy as the backbone of urothelial carcinoma treatment, and the practical problems now are dose optimization, biomarker selection, and sequencing after ADC exposure.

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🗣️ 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).

Update: KEYNOTE-B15/EV-304 discussion shifts to who does NOT benefit from perioperative EV plus pembrolizumab

KEYNOTE-B15/EV-304 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 more grade ≥3 adverse events (75.7% vs 67.2%) in the EV plus pembrolizumab arm over cisplatin-based chemotherapy. Attention has turned to patients who do not achieve pCR, a subgroup in which EV plus pembrolizumab showed little separation from cisplatin-based chemotherapy (HR 0.90), identifying a population with major unmet need. Commentators argue that membranous NECTIN4 expression, NECTIN4 amplification, histologic subtype, and spatial tumor heterogeneity should be integrated to better identify who derives the greatest benefit from perioperative EV-based treatment. The central debate is whether, for MIBC patients who do not achieve pCR on EV plus pembrolizumab, chemoimmunotherapy is a better upfront choice, and whether NECTIN4 expression can identify them before treatment.

Discussed by: @urotoday, @urotoday, @OncoAlert, @OncBrothers, @OncoAlert, @OncoAlert

→ View representative tweet

FDA approves Lu-177 PSMA-617 plus ARPI for PSMA-positive metastatic hormone-sensitive prostate cancer on PSMAddition

The FDA approved lutetium-177 PSMA-617 (Pluvicto, Novartis) in combination with an androgen receptor pathway inhibitor for PSMA-positive metastatic hormone-sensitive prostate cancer, based on the PSMAddition trial (HR PFS 0.72, immature OS). In 1,144 PSMA PET-positive mHSPC patients, the combination of Lu-PSMA-617 plus ADT plus ARPI versus ADT plus ARPI alone met its primary endpoint, with an 8% discontinuation rate; an updated analysis showed the risk of progression or death cut by 33% (HR 0.67), with a still-maturing overall survival trend (HR 0.80). The central debate is which mHSPC patients should be offered radioligand therapy up front rather than at castration resistance, given immature overall survival data. Clinicians also flag that the approval may widen the gap in care standards between rural and community settings versus urban and academic centers.

Discussed by: @EladSharonMD, @neerajaiims, @OncoAlert, @DCockrellMD, @OncBrothers, @urotoday

→ View representative tweet

Milan criteria paper argues cystectomy can be spared in selected MIBC patients with clinical complete response

A paper argues that cystectomy can be spared in selected patients with muscle-invasive bladder cancer who achieve complete response following neoadjuvant therapy, with discussants proposing that a standardized clinical complete response — defined by TURBT biopsies, urine cytology, and imaging as a composite biomarker — could guide bladder-sparing strategies. Against this, panelists counter that the survival benefit of EV plus pembrolizumab was achieved with surgical consolidation, that tumor response does not equal cure, and that outside a clinical trial, cystectomy should not be omitted. The debate centers on whether a standardized clinical complete response is sufficient to safely omit cystectomy today, or whether that decision must await results from EV-309 and NEO-BLAST.

Discussed by: @urotoday, @OncoAlert, @urotoday, @DrOmarMian

→ View representative tweet

TALAPRO-3 in NEJM: talazoparib plus enzalutamide improves radiographic PFS in HRR-altered metastatic hormone-sensitive prostate cancer

In HRR-altered mHSPC, adding talazoparib to enzalutamide plus ADT significantly improved imaging-based progression-free survival versus enzalutamide alone (3-year rates: 77% vs 56%; HR 0.48, P<0.001), reducing the risk of progression or death by 52%; an interim overall survival analysis favored talazoparib (HR 0.77) but was not definitive, and two treatment-related deaths were reported. Toxicity was notably higher with talazoparib, particularly grade ≥3 anemia in 51% of patients. The FDA granted priority review to a supplemental NDA for talazoparib plus enzalutamide in HRR gene-altered mCSPC. The key question is whether upfront PARP intensification should be offered to all HRR-altered mHSPC patients given that grade ≥3 anemia occurred in half of them.

Discussed by: @neerajaiims, @OncoAlert, @neerajaiims, @MedwatchKate

→ View representative tweet

Update: LITESPARK-022 FDA approval and quality-of-life debate now centre on whether CTCAE measures what patients feel

Belzutifan plus pembrolizumab received FDA approval with 2.5-year DFS of 75.8% vs 68.6% (HR 0.72), 2.5-year OS of 95.6% vs 93.8% (HR 0.78), and grade ≥3 adverse events in 42.2% vs 17.9% of patients. Despite more than 50% grade 3–4 toxicity in the pembrolizumab/belzutifan arm of LITESPARK-022, three quality-of-life instruments — FKSI, EORTC QLQ-30, and GP5 — showed only a temporary dip in global and physical/role function that did not reach predefined clinically meaningful levels. This has prompted investigators to propose characterizing toxicity as "life altering" as a more meaningful measure than CTCAE grading alone. The debate is what instrument should decide whether adjuvant belzutifan is worth it if CTCAE grade 3–4 events do not translate into measurable quality-of-life loss.

Discussed by: @OncBrothers, @OncoAlert, @BethN01, @montypal

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RADICAL published in JCO: adding radium-223 to cabozantinib fails in bone-metastatic RCC

Bone metastases occur in approximately 30% of patients with metastatic RCC and are associated with increased skeletal morbidity and worse survival; RADICAL tested whether adding radium-223 to cabozantinib could improve outcomes in this population. The trial stopped early for futility after enrolling 98 patients, with no improvement in symptomatic skeletal event-free survival, overall survival, or response rate. Lower-than-expected skeletal event rates were attributed to the impact of earlier palliative radiotherapy and optimal bone health care. The resulting question is how future bone-targeted trials in metastatic RCC should define a meaningful endpoint when modern supportive care already suppresses skeletal events.

Discussed by: @DrChoueiri, @nataliagandur, @scocmem, @OncoAlert

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Bio-digital avatars for bladder cancer: patient-derived organoids plus AI to forecast resistance

The Weill Cornell/NewYork-Presbyterian group combines patient-derived cancer organoids with AI to create "bio-digital avatars" of each patient's cancer, with the aim of predicting treatment response and personalizing therapy sequencing for bladder cancer. Presented findings show that resistant clones emerge through evolutionary selection under treatment pressure, and SOX2 emerged as a key stemness-associated program linked to resistance. The central question is what prospective validation would make organoid-plus-AI resistance forecasting usable for choosing the next line of bladder cancer therapy.

Discussed by: @FaltasLab, @chavarriagaj, @BrendanGuercio

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First network meta-analysis of perioperative MIBC trials ranks EV plus pembrolizumab highest

Described as the first network meta-analysis of perioperative trials in MIBC, the analysis incorporated 2,293 patients from three randomized controlled trials. Compared with gemcitabine–cisplatin, both enfortumab vedotin–pembrolizumab and gemcitabine–cisplatin plus durvalumab improved overall survival, event-free survival, and pathological complete response, with enfortumab vedotin–pembrolizumab ranking highest across outcomes. The debate is how much weight indirect comparisons across these three perioperative MIBC trials should carry in the absence of any head-to-head trial.

Discussed by: @OncoAlert, @tumayipekci, @OncoAlert

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Sawyers plenary on lineage plasticity: RB1 loss primes prostate cancer for neuroendocrine transition

RB1 loss primes prostate cancer for neuroendocrine transition; removal of extracellular matrix causes ASCL1 induction and progression to neuroendocrine prostate cancer within days, with TIP60/KAT5 inhibition identified as a potential target that kills NEPC via MYC dependency. In the clinic, the phase II CHAMP study of cabazitaxel/carboplatin plus nivolumab/ipilimumab demonstrated encouraging activity in NEPC/AVPC. The open question is whether epigenetic targets such as TIP60/KAT5 can be tested in patients with aggressive-variant prostate cancer if neuroendocrine transdifferentiation proves reversible in the laboratory.

Discussed by: @youngkwangchae, @DrChoueiri

→ View representative tweet

🔥 Top Ranked Tweets

Neeraj Agarwal, MD, FASCO @neerajaiims

RT @OncoAlert: 79.4% vs 66.2%: Could enfortumab vedotin plus pembrolizumab redefine perioperative treatment for bladder cancer?

Enfortumab Vedotin and Pembrolizumab in Cisplatin-Eligible Bladder Cancer

The phase 3 🗝️ KEYNOTE-B15/EV-304 trial found that perioperative enfortumab vedotin plus pembrolizumab 🧪 significantly improved outcomes versus neoadjuvant cisplatin–gemcitabine in cisplatin-eligible muscle-invasive #BladderCancer . Two-year event-free survival was 79.4% versus 66.2%, while overall survival was 86.9% versus 81.3%. Pathologic complete response was also higher (55.8% vs 32.5%), but grade ≥3 adverse events were more frequent, highlighting improved efficacy alongside increased toxicity.

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@Uro_Oncologist

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