📬 GU Oncology Intelligence Digest — Week 2026-W40

FDA approved belzutifan plus lenvatinib in post-IO advanced clear cell RCC on LITESPARK-011 and granted priority review to perioperative durvalumab plus neoadjuvant enfortumab vedotin in MIBC on VOLGA, while NECTIN4 validation, the CIPHER carboplatin trial and a JAMA Network Open cisplatin-versus-carboplatin evidence appraisal drove the week's debates.

⚡ TL;DR

🐦 Twitter / 🦋 Bluesky

Cell-free DNA methylation signals reported years before breast and prostate cancer diagnosis reopen the early-detection argument — The report describes the potential to predict breast and prostate cancer up to 8 years before it is diagnosed from blood cell-free DNA methylation patterns
JAMA Review of cancer vaccines lists prostate and bladder cancer among the few settings with approved uses — The review describes cancer vaccines being evaluated for treatment and prevention across multiple malignant neoplasms, with current approved uses in melanoma, prostate cancer, and bladder cancer
FDA approves belzutifan plus lenvatinib after PD-1/PD-L1 therapy in clear cell RCC, with clinicians flagging the missing overall survival benefit — On September 24, 2026 the FDA approved belzutifan plus lenvatinib for adults with advanced renal cell carcinoma containing a clear cell component after PD-1/PD-L1 inhibitor treatment
FDA priority review for perioperative durvalumab plus neoadjuvant enfortumab vedotin in MIBC puts VOLGA against EV-303 before the data are even presented — FDA granted priority review for VOLGA, in which 3 neoadjuvant cycles of EV and a year of perioperative durvalumab were given for muscle invasive bladder cancer, with the press release stating an EFS and OS advantage
JAMA Network Open appraisal of 11 meta-analyses finds most cisplatin-versus-carboplatin guidance rests on low-certainty evidence — The paper examined the certainty of evidence of the 11 major meta-analyses (12 683 patients) on which guidelines based their cisplatin versus carboplatin recommendations

Full details below ↓

📄 What's Being Published

Manuscripts:

Phase 1 study of KHK2455, a long-acting, potent and selective IDO1 inhibitor, in combination with avelumab in patients with locally advanced or metastatic urothelial carcinoma. — Zakharia Yousef et al., J Immunother Cancer

This multicenter open-label phase 1 enrolled 16 subjects receiving oral KHK2455 at 30, 100, or 200 mg plus avelumab 800 mg biweekly (n=4, 4, and 8 in the 30, 100 and 200 mg cohorts, respectively) in locally advanced or metastatic urothelial carcinoma. No TEAEs were considered related to KHK2455 or avelumab, and four subjects had fatal TEAEs considered not related to treatment. One subject in the 30 mg cohort achieved a complete response and one in the 200 mg cohort achieved a partial response; the subject with CR had the highest baseline Tumor Inflammation Signature score (9.06) compared with 4.8 in the subject with PR, and all 13 evaluable biopsies expressed PD-L1 in at least one compartment, with 31% (4/13) positive on tumor cells and 69.2% (9/13) on tumor-associated immune cells.

Clinical bottom line: This 16-patient phase 1 changes nothing in urothelial carcinoma practice today: IDO1 inhibition with KHK2455 added to avelumab was tolerable and produced one complete and one partial response, so it remains an early-phase signal tied to inflamed tumors rather than a treatment option.

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).

Cell-free DNA methylation signals reported years before breast and prostate cancer diagnosis reopen the early-detection argument

Blood cell-free DNA methylation patterns carry the potential to predict breast and prostate cancer up to 8 years before diagnosis. In the NHS-Galleri RCT of 142,250 patients with a median follow-up of 17 months, the primary endpoint was not met, though a decrease in stage 4 disease was observed alongside 52% PPV and 99.5% specificity; an 80% reduction in metastatic urothelial cancer diagnoses was noted, yet a number needed to treat above 150 and low positive predictive value remain central to the debate about whether an 8-year methylation lead time justifies moving blood-based early detection toward routine clinical use.

Discussed by: @EricTopol, @arnabguonc

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Sources cited: Cell Press

JAMA Review of cancer vaccines lists prostate and bladder cancer among the few settings with approved uses

A JAMA review covering vaccines evaluated for treatment and prevention across multiple malignant neoplasms identifies current approved uses in melanoma, prostate cancer, and bladder cancer, noting that vaccines can stimulate adaptive immunity against neoantigens, nonmutated tumor proteins, or tumor-derived antigens. Long-term follow-up from a randomized phase 2 trial reported extended survival with the pTVG-HP DNA vaccine in PSA-recurrent prostate cancer. Specialists note that CD8 T cells are associated with response to checkpoint inhibitors but not with BCG, suggesting different immunotherapies require different biomarkers — a gap that directly shapes how patient selection should be structured in therapeutic cancer vaccine trials.

Discussed by: @JAMA_current, @weoncologists

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Sources cited: JAMA Network · OncLive

FDA approves belzutifan plus lenvatinib after PD-1/PD-L1 therapy in clear cell RCC, with clinicians flagging the missing overall survival benefit

On September 24, 2026, the FDA approved belzutifan plus lenvatinib for adults with advanced renal cell carcinoma containing a clear cell component after PD-1/PD-L1 inhibitor treatment, based on LITESPARK-011, in which median PFS was 14.6 versus 10.6 months (HR 0.74) and ORR was 53% versus 40% compared with cabozantinib. Median OS was 33.7 versus 28.6 months (HR 0.85, p=0.061), which was not significant at final analysis, while grade ≥3 adverse events occurred in 72% versus 66% of patients; key safety concerns include anemia, hypoxia, cardiac dysfunction, hypertension, and embryo-fetal toxicity. Oncologists acknowledged a 4-month PFS gain, higher ORR (53% vs 40%), and duration of response (23 vs 12 months), but flagged unresolved questions about performance after first-line IO/IO versus IO/TKI and optimal sequencing, with the absence of a significant OS benefit central to the debate about whether this combination should displace cabozantinib in the second-line setting.

Discussed by: @DrChoueiri, @drenriquegrande, @Merck, @scocmem, @OncBrothers, @OncBrothers, @ilyassahinMD, @DrMirallas

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Sources cited: FDA press release · Merck press release · OncLive

FDA priority review for perioperative durvalumab plus neoadjuvant enfortumab vedotin in MIBC puts VOLGA against EV-303 before the data are even presented

The FDA granted priority review for VOLGA, in which 3 neoadjuvant cycles of enfortumab vedotin plus a year of perioperative durvalumab were given for muscle-invasive bladder cancer, with the press release stating an event-free survival and overall survival advantage supported by statistically significant and clinically meaningful improvements in those endpoints. Clinicians noted it was unusual to see a priority review announcement with a PDUFA action date already in Q4 2026 for a study not yet fully presented, and contextualized VOLGA against EV-303, which established perioperative enfortumab vedotin plus pembrolizumab with an EFS HR of 0.40 and OS HR of 0.50 versus radical cystectomy alone — while noting that even in EV-303, only 67% of patients undergoing cystectomy started adjuvant therapy. A dissenting view pointed out that VOLGA does not compare its regimen against enfortumab vedotin plus pembrolizumab, which has already shown a survival benefit and received FDA approval in cisplatin-ineligible MIBC, leaving the relative contribution of the adjuvant component unresolved.

Discussed by: @OncBrothers, @Uromigos, @DrChoueiri, @PGrivasMDPhD, @dr_yakupergun, @OncBrothers, @weoncologists

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JAMA Network Open appraisal of 11 meta-analyses finds most cisplatin-versus-carboplatin guidance rests on low-certainty evidence

A JAMA Network Open paper examined the certainty of evidence underlying the 11 major meta-analyses (12,683 patients) on which guidelines have based their cisplatin-versus-carboplatin recommendations. The only high-certainty evidence signal identified was for cisplatin over carboplatin in objective response rate in urothelial cancer, and for no PFS difference between cisplatin and carboplatin in ovarian cancer; most other guidelines-based recommendations rest on low or ultra-low GRADE evidence. The authors argue that new trials may not be needed, only greater access to data from completed studies — a position that directly challenges whether cisplatin eligibility remains the appropriate gatekeeper for perioperative and first-line regimen selection in bladder cancer.

Discussed by: @scocmem, @DrMirallas

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Sources cited: JAMA Network

Independent European Urology validation in 322 patients makes NECTIN4 a predictive, not merely prognostic, biomarker for EV plus pembrolizumab

In 322 patients receiving first-line enfortumab vedotin plus pembrolizumab for metastatic urothelial cancer, NECTIN4-high tumors had an ORR of 67.4% versus 41.9% and OS of 21.5 versus 14.2 months, with an adjusted OS HR of 0.62; NECTIN4 expression remained independently associated with response and OS in multivariable analyses. Critically, NECTIN4 was not significantly associated with outcome in an independent pembrolizumab-monotherapy cohort, supporting its classification as predictive rather than purely prognostic. Integrating amplification and membranous NECTIN4 has shown correlation with enfortumab vedotin responses, with HER2 described as functioning as a delivery address rather than a classical target — framing the debate over whether NECTIN4 expression is now sufficient to guide front-line patient selection or should be reserved for decisions at progression.

Discussed by: @OncoAlert, @Uromigos, @scocmem

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Sources cited: ScienceDirect

No consensus on adjuvant systemic therapy for upper tract urothelial carcinoma, with nivolumab and carboplatin data both underwhelming

The clinical scenario under debate was a cisplatin-ineligible patient after nephroureterectomy for high-grade T3N0M0 upper tract urothelial cancer with PD-L1-positive, ctDNA-negative disease — a setting where neither available option performs convincingly: nivolumab data in upper tract disease showed a DFS HR of 1.23 (0.67–2.23), and the carboplatin subset of POUT showed an OS HR of 0.87 (0.50–1.53). Although ctDNA appeared to work for UTUC in IM010, it was excluded from IM011 due to concerns from the nivolumab data in this subgroup; one view favored enfortumab vedotin plus pembrolizumab in ctDNA-positive patients with surveillance of ctDNA-negative patients — acknowledged as off protocol. Colleagues responded that a dedicated adjuvant UTUC trial comparing an ADC-IO combination against platinum/IO is needed, with work cited as underway through the EAONC.

Discussed by: @Uromigos, @Uromigos, @scocmem

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🔥 Top Ranked Tweets

OncoAlert @OncoAlert

RT @OncoAlert: 🚨 Five years later, the KEYNOTE-564 question is becoming even harder to ignore: does adjuvant immunotherapy change the long-term trajectory of high-risk ccRCC?

Article📰
https://t.co/hGhJNVXKxR

Adjuvant pembrolizumab for the treatment of clear cell renal cell carcinoma: Five-year results from the phase III KEYNOTE-564 study

With a median 70-month follow-up, KEYNOTE-564 confirms durable benefits from adjuvant pembrolizumab🧪 in clear cell renal cell carcinoma at increased risk of recurrence after surgery. Pembrolizumab 📈 improved disease-free survival (HR 0.71) and overall survival (HR 0.66), with estimated 5-year DFS of 60.9% versus 52.2% and OS of 87.7% 🆚 82.3%. Benefits remained consistent across key subgroups, while safety remained largely unchanged, supporting pembrolizumab as standard care. #KidneyCancer

@tompowles1
@DrChoueiri
@Dr_Tom_Ferguson
@HowardGurney

Pinging our faculty
@apolo_andrea
@neerajaiims
@montypal
@Silke_Gillessen
@AOmlin
@brian_rini
@PGrivasMDPhD
@TiansterZhang
@AlbigesL
@cdanicas
@amerseburger
@sonpavde
@DrDanielHeng
@declangmurphy
@seanmmcbride
@HHammersMD
@shilpaonc
@DrRanaMcKay
@scserendipity1
@DrYukselUrun
@scocmem
@ravikanesvaran
@AmandaNizamMD
@drenriquegrande
@BraunMDPhD
@EfstathiouEleni
@nataliagandur
@crisbergerot

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📬 GU Oncology Intelligence Digest — Week 2026-W40

⚡ TL;DR

📄 What's Being Published

🗣️ What People Were Discussing This Week

Cell-free DNA methylation signals reported years before breast and prostate cancer diagnosis reopen the early-detection argument

JAMA Review of cancer vaccines lists prostate and bladder cancer among the few settings with approved uses

FDA approves belzutifan plus lenvatinib after PD-1/PD-L1 therapy in clear cell RCC, with clinicians flagging the missing overall survival benefit

FDA priority review for perioperative durvalumab plus neoadjuvant enfortumab vedotin in MIBC puts VOLGA against EV-303 before the data are even presented

JAMA Network Open appraisal of 11 meta-analyses finds most cisplatin-versus-carboplatin guidance rests on low-certainty evidence

Independent European Urology validation in 322 patients makes NECTIN4 a predictive, not merely prognostic, biomarker for EV plus pembrolizumab

No consensus on adjuvant systemic therapy for upper tract urothelial carcinoma, with nivolumab and carboplatin data both underwhelming

🔥 Top Ranked Tweets

🧪 Newly Recruiting Trials