📬 GU Oncology Intelligence Digest — Week 2026-W42

FDA approvals landed for durvalumab in BCG-naive high-risk NMIBC (POTOMAC), belzutifan plus pembrolizumab in adjuvant RCC (LITESPARK-022), belzutifan plus lenvatinib in 2L ccRCC (LITESPARK-011), lutetium-177 PSMA-617 in mHSPC (PSMAddition) and ctDNA-guided adjuvant atezolizumab (IMvigor011), while urine cfRNA, PSMA-guided radiotherapy and ESMO26 perioperative bladder trials dominated discussion.

⚡ TL;DR

📄 Publications

Phase I/II Study of Bavdegalutamide, a Proteolysis-Targeting Chimera Androgen Receptor Degrader, in Metastatic Castration-Resistant Prostate Cancer. — Phase I enrolled 95 patients and established bavdegalutamide 420 mg once daily as the recommended phase II dose in mCRPC previously treated with an ARPI

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TROFUSE-055 tests SAC-TMT plus pembrolizumab followed by chemoradiation in NMIBC, and clinicians question the role of chemoRT after an ADC-driven clinical complete response — TROFUSE-055 is a randomized phase 3 non-muscle invasive bladder cancer trial testing SAC-TMT with pembrolizumab, which had a 68% response rate in advanced disease, followed by chemoradiation against a chemoRT control with or without neoadjuvant chemotherapy
Update: urine cell-free RNA uRARE-seq draws a second wave of clinician commentary on false positives, post-treatment surveillance and validation partnerships — uRARE-seq is a tumor-naive liquid biopsy method for analyzing urine cell-free RNA in bladder cancer and other genitourinary cancers, published in Nature Medicine
Three randomized perioperative MIBC trials set for ESMO26 reopen the question of whether PD-1 plus cisplatin reproduces NIAGARA or antagonizes chemotherapy — Three randomized trials in muscle invasive bladder cancer are coming at ESMO26: VOLGA testing neoadjuvant EV plus perioperative durvalumab, and ENERGIZE and KEYNOTE-866 testing cisplatin-based neoadjuvant chemotherapy with or without nivolumab or pembrolizumab
FDA approves belzutifan plus pembrolizumab as adjuvant therapy in RCC on LITESPARK-022, with a DFS gain and immature overall survival — Belzutifan plus pembrolizumab was FDA approved on LITESPARK-022, a phase III versus pembrolizumab in adjuvant RCC, with 2.5-year DFS 75.8% versus 68.6% (HR 0.72)
PSA nadir ≤0.2 ng/mL emerges as an early prognostic marker in mHSPC with large separations in OS and PFS — In mHSPC, PSA nadir ≤0.2 ng/mL was associated with OS of 92.8 versus 34 months (HR 0.27) and PFS not reached versus 12.1 months (HR 0.19)

Full details below ↓

📄 What's Being Published

Manuscripts:

Phase I/II Study of Bavdegalutamide, a Proteolysis-Targeting Chimera Androgen Receptor Degrader, in Metastatic Castration-Resistant Prostate Cancer. — Gao Xin et al., J Clin Oncol

In phase I (N = 95), bavdegalutamide 420 mg once daily was the RP2D in mCRPC previously treated with an ARPI. In phase II, PSA50 and PSA30 rates were 60.0% and 70.0% with AR T878 and/or H875 mutations (n = 20), versus 4.3% and 6.5% with wild-type AR or other AR alterations (n = 46) and 3.1% and 6.3% with AR L702H or AR-V7 (n = 32). Median rPFS in these subgroups was 11.1, 4.2, and 5.1 months, respectively. Among less-pretreated patients (n = 42), PSA50 was 21.4%, PSA30 was 23.8%, and median rPFS was 11.1 months. Among 144 phase II patients, 17.4% had grade 3 TRAEs and none had grade ≥4 TRAEs, with dose reduction in 11.8% and discontinuation in 11.1%.

Clinical bottom line: Bavdegalutamide is an investigational, biomarker-restricted option. Meaningful PSA and rPFS activity is confined to mCRPC with AR T878/H875 ligand-binding-domain mutations, so AR genotyping would be mandatory before any future use.

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Disitamab Vedotin Plus Tislelizumab in Transurethrally Unresectable, ERBB2-Positive, Non-Muscle-Invasive Bladder Cancer: A Nonrandomized Clinical Trial. — Qie Yunkai et al., JAMA Oncol

This single-arm phase 2 Simon 2-stage trial included 28 participants from 137 screened, with a median follow-up of 29.4 months. Complete response of high-risk disease was achieved in 19 of 26 (73.1%; 95% CI, 54.8%-91.3%), meeting the prespecified 70% goal. Among all 28 participants, 19 responded (67.9%). Among responders, 24-month sustained response was 83.5% (95% CI, 68.0%-100.0%), with no muscle-invasive or metastatic progression. Treatment-related adverse events occurred in 25 patients (89.3%), including grade 3 to 4 events in 4 (14.3%), discontinuation in 2 (7.1%), and no grade 5 events.

Clinical bottom line: For the narrow group with transurethrally unresectable ERBB2-positive very-high-risk NMIBC who refuse or cannot have cystectomy, disitamab vedotin plus tislelizumab offers a 73% complete response with durable control. With 28 patients and no randomization, it remains an investigational bridge, not a replacement for cystectomy.

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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).

TROFUSE-055 tests SAC-TMT plus pembrolizumab followed by chemoradiation in NMIBC, and clinicians question the role of chemoRT after an ADC-driven clinical complete response

TROFUSE-055 is a randomized phase 3 NMIBC trial testing SAC-TMT with pembrolizumab, which had a 68% response rate in advanced disease, followed by chemoradiation against a chemoRT control with or without neoadjuvant chemotherapy. Unlike EV-309, which gives no chemoRT in the study arm, it raises an unanswered question: is chemoRT needed after an ADC-driven clinical complete response, and many trials will be needed to define the optimal approach. Bladder-preservation advocates warn that very liberal trimodality criteria predispose patients to failure and more salvage cystectomies. Others frame surgery sparing as a recurring pattern across tumor types, with bladder next because patients want their organs.

Discussed by: @seanmmcbride, @Uromigos, @TylerSbrt, @marklewismd

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Update: urine cell-free RNA uRARE-seq draws a second wave of clinician commentary on false positives, post-treatment surveillance and validation partnerships

uRARE-seq, a tumor-naive urine cfRNA liquid biopsy published in Nature Medicine, drew praise for its independence from tissue. This matters in Ta, small-focus high-grade, or CIS disease, where tumor-informed utDNA is difficult. Proponents cite sensitive MRD detection and immune signatures predicting BCG versus chemotherapy response. Urologists caution that BCG prediction is underpowered, that false positives occurred in non-cancer controls, and that the assay has no post-treatment validation, where surveillance is hardest. Cleveland Clinic Urology plans to partner with Diehn and ReseroBio on further validation.

Key numbers: Sensitivity 95% at 90% specificity · False positives 11% in non-cancer controls

Discussed by: @OncoAlert, @PGrivasMDPhD, @DrewMoghanaki, @weoncologists, @liaojoe1, @SCIDirector

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Sources cited: Nature · Urine cell-free RNA for bladder cancer detection and treatment response prediction (Nature Medicine, 2026)

Three randomized perioperative MIBC trials set for ESMO26 reopen the question of whether PD-1 plus cisplatin reproduces NIAGARA or antagonizes chemotherapy

ESMO26 will feature VOLGA, which compares EV plus durvalumab, EV plus durvalumab plus tremelimumab, and cystectomy. It will also feature KEYNOTE-866 and ENERGIZE, which test gemcitabine-cisplatin with or without pembrolizumab or nivolumab. The question is whether the chemo-plus-PD-1 trials reproduce NIAGARA's OS hazard ratio of 0.75 or show the platinum antagonism seen in metastatic disease. In VOLGA, EV is limited to three neoadjuvant cycles, versus nine in KEYNOTE-905, where perioperative EV-pembrolizumab gave an OS HR of 0.5-0.6. The debate is whether lower EV exposure is a fair trade, especially since VOLGA has no EV-pembrolizumab comparator despite that regimen's FDA approval.

Discussed by: @tompowles1, @weoncologists, @dr_yakupergun, @OncUpdates

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FDA approves belzutifan plus pembrolizumab as adjuvant therapy in RCC on LITESPARK-022, with a DFS gain and immature overall survival

The FDA approved belzutifan plus pembrolizumab based on LITESPARK-022, a phase III trial against 1 year of pembrolizumab in adjuvant RCC. DFS improved, but OS remains immature with median not reached. Grade ≥3 toxicity rose substantially, and a subset of patients required packed red blood cells or erythropoiesis-stimulating agents. Clinicians debate whether the DFS gain justifies adding a year of belzutifan given the toxicity cost.

Key numbers: 2.5-yr DFS 75.8% vs 68.6%, HR 0.72 · 2.5-yr OS 95.6% vs 93.8%, HR 0.78 · Grade ≥3 AEs 42.2% vs 17.9% · ~12% PRBC/ESA

Discussed by: @OncBrothers, @DrKarineTawagi, @MikeSerzanMD

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PSA nadir ≤0.2 ng/mL emerges as an early prognostic marker in mHSPC with large separations in OS and PFS

Reaching the PSA nadir threshold was associated with markedly longer OS and PFS in mHSPC, supporting it as an early prognostic marker. Clinicians discussed PSA monitoring as a guide to treatment decisions. Others noted that no biomarker is perfect, citing a U-shaped association of PSA with prostate cancer-specific mortality in Gleason 8-10 disease in the PET era. The open question is whether failing to reach the nadir should trigger intensification or remain purely prognostic.

Key numbers: OS 92.8 vs 34 mo, HR 0.27 · PFS NR vs 12.1 mo, HR 0.19

Discussed by: @g_procopio_, @jjnaylor02, @urotoday

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PROpel non-BRCA subgroup analysis published, with an rPFS gain but no overall survival difference

In the post hoc, exploratory non-BRCA-mutated PROpel subgroup, olaparib plus abiraterone improved rPFS over abiraterone alone with no new safety signals. OS did not differ significantly. HRR/BRCA testing still guides who benefits most, and clinicians argue that HRR-positive is not one biology, so the gene and disease state matter. The debate is whether the combination should be offered to non-BRCA mCRPC at all.

Key numbers: rPFS 24.1 vs 19.0 mo, HR 0.76 · OS 39.6 vs 38.0 mo, HR 0.91 (NS)

Discussed by: @g_procopio_, @urbano_anido, @ChandrakanthMv

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Sources cited: Elsevier

🔥 Top Ranked Tweets

UroToday.com @urotoday

Lutetium-177-PSMA-617 radiographic PFS benefit in the #PSMAddition trial for metastatic hormone-sensitive #ProstateCancer. @DrScottTagawa @WeillCornell joins @CaPsurvivorship @DanaFarber to discuss the PSMAddition FDA approval. The study enrolled patients with PSMA-positive #mHSPC on an ADT plus ARPI doublet and randomized them to addition of up to six cycles of lutetium-177 PSMA-617; any ARPI was permitted. #WatchNow on UroToday > https://t.co/9sts1AdWrF

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📬 GU Oncology Intelligence Digest — Week 2026-W42

⚡ TL;DR

📄 What's Being Published

🗣️ What People Were Discussing This Week

TROFUSE-055 tests SAC-TMT plus pembrolizumab followed by chemoradiation in NMIBC, and clinicians question the role of chemoRT after an ADC-driven clinical complete response

Update: urine cell-free RNA uRARE-seq draws a second wave of clinician commentary on false positives, post-treatment surveillance and validation partnerships

Three randomized perioperative MIBC trials set for ESMO26 reopen the question of whether PD-1 plus cisplatin reproduces NIAGARA or antagonizes chemotherapy

FDA approves belzutifan plus pembrolizumab as adjuvant therapy in RCC on LITESPARK-022, with a DFS gain and immature overall survival

PSA nadir ≤0.2 ng/mL emerges as an early prognostic marker in mHSPC with large separations in OS and PFS

PROpel non-BRCA subgroup analysis published, with an rPFS gain but no overall survival difference

🔥 Top Ranked Tweets

🧪 Newly Recruiting Trials