📬 GU Oncology Intelligence Digest — Week 2026-W35

ENZAMET reports 8-year survival with enzalutamide in mHSPC, FASTRACK II delivers 100% local control at 5 years for kidney SBRT, and the first positive individualized neoantigen therapy trial in melanoma redirects attention to ongoing RCC and bladder vaccine studies.

⚡ TL;DR

📄 Publications

Eight-year outcomes of testosterone suppression plus enzalutamide or a non-steroidal anti-androgen for metastatic, hormone-sensitive prostate cancer (ENZAMET; ANZUP 1304). — At a median follow-up of 8.1 years, median OS 7.9 vs 5.8 years and 8-year OS 50% vs 40% with enzalutamide versus NSAA (HR 0.73)

🐦 Twitter / 🦋 Bluesky

FASTRACK II final results: 100% local control and 100% cancer-specific survival at 5 years with kidney SBRT — With median follow-up of 5 years, FASTRACK II reported no local recurrences at 36, 60 or 84 months, 100% cancer-specific survival, and grade 3 AEs at 10%
First positive individualized neoantigen therapy trial in melanoma redirects attention to the INTerpath RCC and bladder studies — Personalized mRNA-based neoantigen vaccines plus pembrolizumab are being tested in randomised adjuvant bladder and renal trials, and the first positive trial was announced in melanoma
Update: hereditary RCC algorithm keeps circulating as a clinic-and-exam reference for genotype-driven surveillance — The algorithm advises VHL imaging from age 15 with intervention around 3 cm and nephron-sparing surgery, Birt-Hogg-Dube renal imaging every 3 years from age 20, and TSC renal imaging every 1-3 years from age 12
Panitumumab-based EGFR blockade in renal medullary carcinoma published in Clinical Cancer Research — A study of panitumumab-based EGFR blockade in renal medullary carcinoma has been published in Clinical Cancer Research
Positive surgical margins after partial nephrectomy quadruple local recurrence risk but do not track with systemic progression — In 1,441 RCC patients treated over 24 years with 5.6% positive surgical margins, PSM carried a 4-fold higher risk of local recurrence with no significant association with systemic progression, cancer-specific or overall mortality

Full details below ↓

📄 What's Being Published

Manuscripts:

Eight-year outcomes of testosterone suppression plus enzalutamide or a non-steroidal anti-androgen for metastatic, hormone-sensitive prostate cancer (ENZAMET; ANZUP 1304). — Zhang A Y et al., Ann Oncol

At a median follow-up of 8.1 years, OS was longer with enzalutamide than NSAA (median 7.9 vs 5.8 years; 8-year OS 50% vs 40%; HR 0.73, 95% CI 0.63 to 0.86; p=0.0001), and clinical PFS at 8 years also favoured enzalutamide (43% vs 20%; HR 0.49, 95% CI 0.42 to 0.57; p<0.0001). Median treatment duration was 4.8 years with enzalutamide versus 1.9 years with NSAA; of 185 participants still receiving enzalutamide at data cut-off, 163 (88%) remained on the full 160 mg dose. Rates of grade 3–5 adverse events per 100 person-years were similar between groups for cardiac (2.2 vs 2.2) and nervous system disorders (2.3 vs 2.0), with more falls observed with enzalutamide (0.70 vs 0.24).

Clinical bottom line: Eight-year ENZAMET data settle the durability question for upfront enzalutamide in metastatic hormone-sensitive prostate cancer: the survival gain persists, most long-term responders stay on full dose, and there is no excess non-prostate-cancer mortality.

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APUC-6 Genes as a Potential Prognostic and Predictive Biomarker in the CHAARTED Prostate Cancer Trial. — Shi Xiaolei et al., JCO Precis Oncol

Transcriptomic data from 160 patients in the phase III CHAARTED trial were analyzed and stratified by APUC-6 and AR expression. Patients with APUC-6-high/AR-low expression showed significantly improved time to castration-resistant prostate cancer (HR 0.43, 95% CI 0.22 to 0.82; p=0.0092), time to clinical recurrence (HR 0.56, 95% CI 0.32 to 1; p=0.049), and OS (HR 0.31, 95% CI 0.16 to 0.61; p=0.0003), but did not appear to benefit from the addition of docetaxel. Statistical interaction analysis supported that patients with APUC-6-low/AR-low expression were more likely to benefit from docetaxel (HR 0.36, 95% CI 0.19 to 0.66; p=0.001).

Clinical bottom line: A six-gene androgen-production panel combined with AR expression splits metastatic castration-sensitive prostate cancer into groups that do and do not gain from adding docetaxel, giving transcriptomics a concrete role in the doublet-versus-triplet decision.

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Expression patterns of potential targets for antibody-directed therapy in metastatic castration-resistant prostate cancer patients. — van Dijk Tanja C et al., Eur J Cancer

Gene expression of 62 antibody-targetable proteins was analyzed in 296 mCRPC biopsies. Established targets KLK2, FOLH1 (PSMA), and STEAP1 showed the highest median expression across the cohort. Notably, CD46 was highly expressed in tumors with low KLK2, FOLH1, and STEAP1 expression, a subgroup associated with poor prognosis.

Clinical bottom line: Antibody target expression in mCRPC tracks with transcriptomic subtype rather than genomic alterations, and CD46 is the target worth pursuing for the PSMA/STEAP1-low, poor-prognosis tumors that current agents miss.

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🗂 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).

FASTRACK II final results: 100% local control and 100% cancer-specific survival at 5 years with kidney SBRT

With a median follow-up of 5 years, FASTRACK II reported no local recurrences at 36, 60, or 84 months, 100% cancer-specific survival, and grade 3 adverse events remaining at 10%. Running alongside this, 25-year prospective NCI data supporting a 3 cm rule in bilateral multifocal papillary RCC reinforce the argument that kidney cancer does not mandate automatic surgery. The central question is whether 5-year 100% local control is sufficient to move SBRT from a surgical alternative for the unfit to a genuine option for operable primary RCC.

Discussed by: @_ShankarSiva, @drphil_urology

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First positive individualized neoantigen therapy trial in melanoma redirects attention to the INTerpath RCC and bladder studies

Personalized mRNA-based neoantigen vaccines plus pembrolizumab are being tested in randomized adjuvant trials across multiple tumor types, and the first positive pivotal trial — reporting a relapse-free survival improvement in melanoma from Merck/Moderna — was announced this week. In GU oncology, INTerpath-004 is a randomized, double-blind phase II study evaluating adjuvant V940 plus pembrolizumab versus placebo plus pembrolizumab following nephrectomy in patients with RCC at increased risk of recurrence, with disease-free survival as the primary endpoint; INTerpath-011 is a randomized phase II study of V940 plus BCG versus BCG alone in treatment-naive high-risk non-muscle-invasive bladder cancer; and INTerpath-005 is evaluating V940 plus pembrolizumab versus pembrolizumab in muscle-invasive urothelial carcinoma. One reading is that INTerpath-011 may be the most informative of the three: if a personalized neoantigen vaccine adds anything on top of BCG, it would indicate that the ceiling of BCG has been about the response lacking tumor specificity rather than insufficient immune activation. If individualized neoantigen therapy works in RCC — a tumor without high mutational burden — the question of which patients should be selected for these vaccines becomes central to the field.

Discussed by: @OncoAlert, @OncoAlert, @BalazsHalmosMD, @OncoAlert, @OncoAlert

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Update: hereditary RCC algorithm keeps circulating as a clinic-and-exam reference for genotype-driven surveillance

A widely shared hereditary RCC surveillance algorithm specifies VHL imaging from age 15 with intervention around 3 cm and nephron-sparing surgery; Birt-Hogg-Dubé renal imaging every 3 years from age 20; and TSC renal imaging every 1–3 years from age 12. FH-deficient RCC/HLRCC is the major exception — no size-based surveillance threshold applies, with annual imaging from age 8–10 and prompt aggressive surgery. A parallel Lynch syndrome surveillance cohort of 517 carriers found a 4.16% annual cancer incidence, with 34% of cancers arising outside guideline-surveilled organs; separately, more than 9% of unselected patients with urinary tract cancer carried a germline pathogenic variant, with approximately 0.7% consistent with Lynch syndrome and 6–8% carrying a DDR variant, and more than a third of patients are missed with current NCCN and EAU guidelines. The open question is whether germline-driven surveillance in GU cancers should be broadened beyond the kidney and urinary tract when a third of Lynch-associated cancers arise outside surveilled organs.

Discussed by: @OncoAlert, @OncoAlert, @VivekSubbiah

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Panitumumab-based EGFR blockade in renal medullary carcinoma published in Clinical Cancer Research

A study of panitumumab-based EGFR blockade in renal medullary carcinoma has been published in Clinical Cancer Research. Investigators emphasize that conducting trials in non-clear cell kidney cancer requires multi-institution collaboration, and a SoCal network has been established for GU research toward that end. The practical debate is whether EGFR-directed therapy can be positioned in renal medullary carcinoma in the absence of a randomized trial, given the rarity of the disease.

Discussed by: @PavlosMsaouel, @montypal

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Positive surgical margins after partial nephrectomy quadruple local recurrence risk but do not track with systemic progression

In a series of 1,441 RCC patients treated over 24 years, a positive surgical margin rate of 5.6% was associated with a 4-fold higher risk of local recurrence, yet carried no significant association with systemic progression, cancer-specific mortality, or overall mortality. Separately, 25-year prospective NCI data supporting the 3 cm intervention threshold in bilateral multifocal papillary RCC demonstrate excellent oncologic outcomes and minimized cumulative harms of repeat treatment, reinforcing a conservative approach to local disease. The operative question is whether a positive margin after partial nephrectomy justifies anything beyond intensified imaging surveillance.

Discussed by: @ChiaraRe, @drphil_urology

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SPP1+ macrophage-rich, T-cell-suppressed tumors in urothelial cancer link IL-6/CRP blood markers to immunotherapy resistance

High IL-6/CRP tracks with SPP1+ macrophage-rich, T-cell-suppressed tumors in urothelial cancer across immune checkpoint blockade cohorts, connecting routine blood biomarkers to an immunosuppressive tumor microenvironment and a potentially targetable axis of resistance to immunotherapy. A separate study examining immune cells surrounding bladder tumors identifies a contribution to chemotherapy resistance and points to a potential therapeutic target. The clinical debate is whether routine inflammatory blood markers such as IL-6 and CRP could be used to stratify urothelial cancer patients before starting checkpoint inhibition.

Discussed by: @OncoAlert, @stolaney1

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ARPI toxicity tables and metabolic monitoring become the practical focus of long-term prostate cancer therapy

A ToxCheck discussion covered dosing, adverse events, and clinical management pearls for abiraterone, apalutamide, darolutamide, and enzalutamide in prostate cancer. Long-term ARPI management recommendations include monitoring cardiovascular and metabolic health, bone health, and quality of life alongside imaging. As men remain on these agents for years, the practical debate concerns which toxicity monitoring should be treated as mandatory rather than discretionary.

Discussed by: @OncBrothers, @OncoAlert

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ENZAMET at 8.1 years: enzalutamide survival gain holds, and clinicians pivot to long-term monitoring and PSA-discordant progression

Mature 8-year ENZAMET data show OS of 50% vs 40% (HR 0.73), with 43% of patients clinically progression-free and one third still on enzalutamide — 88% of them at full dose. Median OS was 7.9 vs 5.8 years, with OS HR 0.73, clinical PFS HR 0.49, and PSA-PFS HR 0.48; benefit persisted across key subgroups including patients who received early docetaxel, though docetaxel was not randomized in ENZAMET and the trial should not be used to estimate its incremental benefit. PSA ≤0.2 ng/mL at 7 months identified patients with particularly favorable long-term outcomes. Radiographic progression without prior or concurrent PSA progression occurred in 10% of all patients and accounted for approximately 30% of observed progression events; among enzalutamide-treated patients who developed radiographic progression in ARCHES, 25% had no PSA rise and 62% did not meet conventional PSA-progression criteria. With a third of men still on enzalutamide at 8 years, clinicians are debating how frequently imaging should be repeated in patients whose PSA remains suppressed.

Discussed by: @OncoAlert, @OncoAlert, @K_Yadavir, @OncoAlert

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SBRT in five fractions matches but does not beat conventional fractionation for 3-year control in favorable intermediate-risk prostate cancer

In favorable intermediate-risk prostate cancer, 5-fraction SBRT versus 20–28 fractions was far more convenient but not superior for 3-year disease control — the gain is in time, not tumor control. A separate randomized trial, RadTARGET, is now underway testing tumor-focused radiotherapy for prostate cancer. The residual clinical question is which patients should still be offered 20–28 fractions if ultrahypofractionation delivers convenience rather than superior control.

Discussed by: @neerajaiims, @TylerSbrt

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🔥 Top Ranked Tweets

OncoAlert @OncoAlert

RT @niklas_kluemper: 🚨 EV+P is practice-changing in MIBC. Now we need to learn how much EV each patient actually needs.

The updated FDA label provides an important perspective on peripheral neuropathy (PN):

Perioperative MIBC (EV-303/304 pooled)
• PN: 42%
• Grade ≥2: 17%
• complete resolution: 41%

la/mUC (EV-302/103 pooled)
• PN: 67%
• Grade ≥2: 43%
• complete resolution: 13%

Reassuringly, PN appears substantially more reversible with finite perioperative EV exposure. But 59% still had residual neuropathy at last assessment, and among those, 30% remained Grade ≥2.

And Grade ≥2 PN matters—this is no longer just tingling. It can interfere with instrumental daily activities: walking longer distances, driving, working, writing/typing or other fine-motor tasks.

Importantly, median onset of Grade ≥2 PN in MIBC was 4.9 months. Given only 3–4 neoadjuvant EV cycles in EV-303/304, this timing suggests that a substantial part of clinically relevant cumulative neurotoxicity may emerge during the postoperative/adjuvant treatment period.

🎯 This raises an important question for the next generation of perioperative trials:

Does every patient need all 9 cycles of EV?

Can pCR, ctDNA/MRD, pathology or molecular biomarkers identify patients in whom EV can be safely de-escalated after surgery?

VOLGA will provide interesting complementary information because its experimental arms use EV preoperatively but not postoperatively—although it does not directly randomize adjuvant EV vs no adjuvant EV, so it cannot answer this question alone.

We have a highly effective, practice-changing regimen. Now precision oncology should help us preserve efficacy while minimizing cumulative toxicity—especially neuropathy in patients we aim to cure. 🔬

More treatment is not necessarily better treatment. The right treatment intensity for the right patient should be the next goal!

@OncoAlert @weoncologists @DrChoueiri @tompowles1 @MattGalsky @apolo_andrea @UroDocAsh @urotoday @Uromigos @Markuseckstein3 @katy_beckermann @ViktorGruenwald @drenriquegrande @DrYukselUrun @Uroweb

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