📬 GU Oncology Intelligence Digest — Week 2026-W41

ASTRO 2026 dominated GU this week with PACE-A, RTOG 0534 PAM50, RTOG 0815 and post-prostatectomy SBRT data, alongside a Nature Medicine urine cfRNA bladder cancer assay, the STAMINA lifestyle RCT in men on ADT, and FDA priority review for VOLGA.

⚡ TL;DR

📄 Publications

Urine cell-free RNA for bladder cancer detection and treatment response prediction. — uRARE-seq was applied to 683 urine samples from patients with cancer and controls

🐦 Twitter / 🦋 Bluesky

Update: VOLGA gets FDA priority review with a press-released EFS and OS advantage, and clinicians note there is no post-cystectomy enfortumab vedotin — FDA granted priority review for VOLGA, in which 3 neoadjuvant cycles of enfortumab vedotin and a year of perioperative durvalumab were given for muscle-invasive bladder cancer, with a press release stating an EFS and OS advantage
Tumor-naive neoantigen vaccines from blood instead of a tumor biopsy draw attention from the RCC community — Personalized neoantigen vaccines have improved outcomes in refractory malignant melanoma and in pilot studies of pancreatic cancer, glioblastoma, renal cell carcinoma and triple negative breast cancer, but require a tumor biopsy to identify the antigens
Post-prostatectomy SBRT in 5 fractions: POPART reports 8.5% late grade 2+ GU toxicity and 74% 30-month biochemical control — POPART reported 100 patients treated with prostate-bed SBRT at 32.5 Gy in 5 fractions, with late grade 2 or worse GU toxicity of 8.5%, only 1 late G2 GI event, 3 in-field relapses and 30-month biochemical control of 74%
Nature Medicine uRARE-seq urine cell-free RNA detects 95% of localized bladder cancers and predicts BCG versus chemotherapy response — uRARE-seq is a tumor-naive liquid biopsy method for analyzing urine cell-free RNA in bladder cancer and other genitourinary cancers
STAMINA randomised trial shows a 12-month supervised exercise and diet programme improves quality of life and fatigue in men on ADT — The STAMINA trial evaluated whether a 12-month lifestyle intervention could improve quality of life and fatigue in men with prostate cancer receiving androgen deprivation therapy, across 15 NHS trusts and 700 participants

Full details below ↓

📄 What's Being Published

Manuscripts:

Cancer and the microbiome: from association to intervention. — Moradi Ali et al., Lancet Oncol

In melanoma, non-small-cell lung cancer and renal cell carcinoma, higher microbial diversity, ecological stability and enrichment of immunostimulatory pathways have been associated with improved immune checkpoint inhibitor response and survival. Antibiotics and proton pump inhibitors are linked to inferior outcomes because they disrupt the microbiome. Microbiome-directed interventions are still investigational. These include faecal microbiota transplantation, dietary modification, prebiotics, probiotics and live biotherapeutic products.

Clinical bottom line: This review changes nothing today for RCC patients on checkpoint inhibitors. It does support caution with unnecessary antibiotics and proton pump inhibitors during immunotherapy.

Read full article →

Urine cell-free RNA for bladder cancer detection and treatment response prediction. — Liu Kevin J et al., Nat Med

uRARE-seq, a urine cfRNA liquid biopsy method, was applied to 683 urine samples from patients with cancer and controls. It demonstrated 95% sensitivity at 90% specificity for detecting localized bladder cancer. It outperformed urine tumor DNA analysis and was unaffected by field-effect mutations. In pretreatment urine from 114 patients, a biomarker predicting likelihood of response to BCG versus chemotherapy reached an area under the curve of 0.93. Complete responders to BCG showed enriched T cell and immune signatures, while nonresponders showed higher expression of proliferation-related genes.

Clinical bottom line: This tissue-free urine cfRNA assay has 95% sensitivity for localized bladder cancer and adds a BCG-versus-chemotherapy response predictor, making it the most compelling urinary biomarker to date. It is not ready to replace cystoscopy until prospective validation is done.

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🔗 Also discussed on social media →

Real-World Comparative Effectiveness of Abiraterone, Apalutamide, Enzalutamide, and Docetaxel Doublets for Metastatic Hormone-Sensitive Prostate Cancer. — Nwogu Ifechukwu B et al., JCO Oncol Pract

Among 9,141 US men with mHSPC, ARPI doublets showed superior PFS versus docetaxel doublets, with no significant differences among ARPI regimens:

Abiraterone: aHR 0.60 [95% CI, 0.55 to 0.66]
Apalutamide: aHR 0.64 [95% CI, 0.56 to 0.73]
Enzalutamide: aHR 0.57 [95% CI, 0.51 to 0.64]

Time to new treatment also favored ARPI doublets (abiraterone aHR 0.46; apalutamide aHR 0.53; enzalutamide aHR 0.47). OS was comparable across all doublets, and neither PFS nor OS differed by timing of disease.

Clinical bottom line: In routine US practice, ARPI doublets delay progression to castration resistance better than docetaxel doublets, with no overall survival difference. No single ARPI distinguished itself, so choosing among abiraterone, apalutamide and enzalutamide remains a toxicity and access decision.

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Palliative Care for Advanced Cancer in Medicare Advantage and Physician Networks. — Hu Xin et al., JAMA Netw Open

This SEER-Medicare cohort included 135 402 beneficiaries with distant-stage cancers: 32.3% were in Medicare Advantage (MA) and 67.7% in traditional Medicare. MA beneficiaries had a higher 6-month cumulative incidence of palliative care (13.3% vs 9.3%; AHR 1.39). After matching on treating oncologist, this difference disappeared (AHR 1.05, 95% CI 0.98-1.12). Other differences persisted: MA beneficiaries had lower systemic therapy receipt (-5.38 percentage points) and higher hospice enrollment (3.42 percentage points).

Clinical bottom line: For men with metastatic prostate cancer, the apparent palliative care advantage of Medicare Advantage reflects which oncologists are in network. Lower systemic therapy use and higher hospice enrollment persist regardless of oncologist, a plan-level effect clinicians should weigh when counseling patients.

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).

Update: VOLGA gets FDA priority review with a press-released EFS and OS advantage, and clinicians note there is no post-cystectomy enfortumab vedotin

The FDA granted priority review to perioperative durvalumab plus neoadjuvant enfortumab vedotin in muscle-invasive bladder cancer patients who are ineligible for or declined cisplatin-based chemotherapy. A press release claims an EFS and OS advantage in VOLGA (n=695, company-reported), with a decision expected Q4 2026 and full data pending. Clinicians point out that the regimen uses just 3 neoadjuvant EV cycles and no EV after cystectomy, which makes the reported benefit notable. That raises the question of how much enfortumab vedotin is actually needed post-cystectomy, and how VOLGA will be reconciled with ctDNA data from perioperative EV plus pembrolizumab trials.

Discussed by: @nataliagandur, @DrYukselUrun, @PGrivasMDPhD, @scocmem, @urbano_anido

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Sources cited: AstraZeneca press release · Cancer Network

Tumor-naive neoantigen vaccines from blood instead of a tumor biopsy draw attention from the RCC community

Personalized neoantigen vaccines have improved outcomes in refractory melanoma and in pilot studies of pancreatic cancer, glioblastoma, renal cell carcinoma and triple negative breast cancer, but they require a tumor biopsy. A new study shows the antigens can be identified from a blood sample instead. In parallel, GU liquid biopsy discussion frames tissue-free testing as the real unlock. The open question is whether blood-based neoantigen calling makes vaccines feasible for RCC patients whose only tissue is an old nephrectomy specimen.

Discussed by: @EricTopol, @akfsurgeon

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Sources cited: Peripheral Blood as the Sole Source for Cancer Neoantigen and Reactive T-Cell Discovery (Cancer Discovery, 2026)

Post-prostatectomy SBRT in 5 fractions: POPART reports 8.5% late grade 2+ GU toxicity and 74% 30-month biochemical control

The prospective multicenter POPART trial treated 100 patients with prostate-bed SBRT at 32.5 Gy/5 fx for biochemical recurrence. It reported low late GU and GI toxicity and few in-field relapses. Across 3 prospective studies, the signal is consistent: StereoBed randomized data show no PRO or toxicity penalty, and POPART/esSBRT show few local failures. The debate is whether 5-fraction prostate-bed SBRT is ready to replace conventional salvage schedules, or whether biochemical control at this follow-up is too immature to act on.

Key numbers: Late ≥G2 GU toxicity 8.5% · Late G2 GI events: 1 · In-field relapses: 3 · 30-mo biochemical control 74%

Discussed by: @TylerSbrt, @TylerSbrt, @urotoday

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Nature Medicine uRARE-seq urine cell-free RNA detects 95% of localized bladder cancers and predicts BCG versus chemotherapy response

uRARE-seq is a tumor-naive liquid biopsy for urine cell-free RNA in bladder and other GU cancers. It outperformed urine tumor DNA analysis and was unaffected by field-effect mutations. Pretreatment urine from 114 patients yielded a predictor of BCG versus chemotherapy response. Clinicians call the tissue-free design the real unlock but want the response prediction tested prospectively. The question is whether the assay can reduce surveillance cystoscopies in NMIBC or should stay confined to trials for now.

Key numbers: Localized bladder cancer sensitivity 95% at 90% specificity · BCG vs chemotherapy response AUC 0.93

Discussed by: @max_diehn, @OncoAlert, @akfsurgeon

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STAMINA randomised trial shows a 12-month supervised exercise and diet programme improves quality of life and fatigue in men on ADT

Across 15 NHS trusts and 700 participants, the intervention combined supervised aerobic and resistance exercise, dietary advice and behavioural support. Compared with Optimised Usual Care, it significantly improved prostate cancer-specific quality of life and reduced fatigue. The programme was feasible within NHS cancer services, with no treatment-related deaths. Clinicians frame STAMINA as yet another positive lifestyle trial for men on ADT at high risk of toxicity. The question is whether such programmes should now be prescribed and funded as part of ADT rather than offered as general advice.

Key numbers: Fatigue cut by 30% · Quality of life improved by 37%

Discussed by: @TylerSbrt, @weoncologists, @healthcaretoday.bsky.social

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Sources cited: The Lancet

HRR testing in prostate cancer: BRCA2 carries the strongest signal and HRR+ is not a single PARP strategy

HRR is not one biology: BRCA2 carries the strongest therapeutic signal, and germline plus tumor testing gives a more complete assessment. Clonal evolution under treatment pressure can change the HRR landscape. AMPLITUDE (niraparib + abiraterone) and TALAPRO-3 (talazoparib + enzalutamide) are both positive Phase III trials for radiographic progression or death. Neither has yet shown an overall survival benefit. BRCA2 and CDK12 alterations appear to drive the benefit, and talazoparib's greater PARP-trapping potency may explain both its efficacy and its hematologic toxicity. This leaves open whether the combination should be reserved for those alterations rather than given to all HRR-mutated patients.

Key numbers: rPFS/death risk reduction up to 48% (BRCA-mutated) · up to 37% (HRR-mutated)

Discussed by: @ChandrakanthMv, @OncoAlert, @urotoday

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PACE-A plenary at ASTRO 2026 puts a 48% versus 8% pad-use gap between prostatectomy and 5-fraction SBRT in front of patients

PACE-A efficacy results were presented in the ASTRO 2026 plenary, with sexual function in the late-breaking abstract. The take-home message: give patients the data and let them choose. At 5 years, pad use was far more common after contemporary prostatectomy than after 36.25 Gy in 5 fractions, roughly one in two versus fewer than one in ten. Discussants argue that patient values favoring surgery are real but must sit next to these figures, not replace them. A counterpoint stresses that most surgical pad users used a single pad, which is very different from severe incontinence, and that surgery and radiation cause different urinary toxicities. The open question is whether every surgery-eligible man should meet a radiation oncologist before consenting to prostatectomy.

Key numbers: ≥1 pad/day at 5 years 48% vs 8% · Surgical pad users on only 1 pad/day: 15 of 16

Discussed by: @nickva1, @jryckman3, @jryckman3

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RTOG 0534 post hoc analysis: PAM50 Luminal B predicts who benefits from ADT added to post-prostatectomy radiotherapy

Among 709 profiled patients in NRG/RTOG 0534 SPPORT, PAM50 Luminal B was both prognostic and predictive of benefit from short-term ADT ± pelvic nodal RT. LumB tumors derived a much larger absolute gain in freedom from progression and metastasis-free survival, independently validating NRG-GU006. Clinicians call it a biomarker with real value for selecting patients for ADT with post-prostatectomy RT. An open question is how PAM50 fits with Decipher-plus-PSA approaches before it is ordered routinely.

Key numbers: 5-y FFP benefit 31% vs 10%, p-int=.01 · 10-y MFS benefit 20% vs −3%, p-int=.05

Discussed by: @TylerSbrt, @lauren_henke, @nataliagandur, @TylerSbrt

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RTOG 0815 long-term results: short-term ADT improves PFS and MFS but not OS, and Decipher identifies who gains metastasis-free benefit

Daniel Krauss presented RTOG-0815 long-term results: short-term ADT improves PFS and MFS but not OS, and it is not worse for non-prostate-cancer death. No clear subgroup failed to benefit. A secondary analysis found the Decipher score predictive of ADT benefit for preventing metastasis in intermediate-risk disease. The question is whether Decipher should now decide which intermediate-risk men receive hormone therapy with definitive radiotherapy.

Discussed by: @TylerSbrt, @TylerSbrt, @TylerSbrt

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Sources cited: OncoDaily

TroFuse-055 opens: phase III of neoadjuvant sacituzumab tirumotecan plus subcutaneous pembrolizumab with chemoradiation for bladder preservation in MIBC

TroFuse055 is a Phase III trial in MIBC patients who have elected to avoid radical cystectomy. It tests neoadjuvant sacituzumab tirumotecan, a Trop2-binding ADC with a belotecan topoisomerase-1 inhibitor payload, plus MK3475A (subcutaneous pembrolizumab), followed by consolidation MK3475A with conventional chemoradiotherapy. Clinicians argue that more randomized trials should focus on improving trimodality therapy, systemic integration and long-term bladder-intact survival. The debate is whether adding the ADC improves bladder-intact survival or simply imports ADC toxicity into a curative setting.

Discussed by: @sonpavde, @OncoAlert

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NRG GU002: adding docetaxel to salvage radiotherapy plus ADT shows minimal benefit overall, with a Decipher interaction and early closure for poor accrual

NRG GU002 showed minimal overall benefit from adding docetaxel to salvage RT plus ADT, with the expected increase in high-grade toxicity. Patients with low/intermediate Decipher scores appeared to benefit most, with a significant interaction. The trial was substantially under-accrued and closed early because providers and patients did not want to add chemotherapy. Separately, a secondary analysis of RTOG 0815 found Decipher predictive of ADT benefit. The question is whether this early-closed trial's Decipher interaction should revive docetaxel in the salvage setting.

Discussed by: @OncoAlert, @TylerSbrt

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EZH2 inhibition in phenotypically plastic prostate cancer requires co-targeting PI3K/mTORC1

Preclinical work shows adaptive PI3K/mTORC1 signaling mediates lineage transition under EZH2 inhibition. Co-targeting with PI3K/mTORC1 inhibitors was effective in aggressive prostate cancer models. In the clinic, phase 2 data showed mevrometostat added to enzalutamide improved rPFS from 6 months to 14.3 months versus enzalutamide alone in 80 abiraterone-pretreated mCRPC patients. MEVPRO-3 is now enrolling 1,000 newly diagnosed mHSPC patients, randomized to ADT + enzalutamide with or without mevrometostat. The question is whether the MEVPRO trials are testing the wrong combination.

Discussed by: @EladSharonMD, @urotoday, @urotoday

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Sources cited: Cell Press

STEEL: adding 24 months of enzalutamide to ADT plus salvage radiotherapy improves early PFS (HR 0.62) but raises grade 3 AEs from 19% to 30%

In STEEL, adding 24 months of enzalutamide to ADT plus salvage RT improved an early PFS endpoint at the cost of more grade 3 adverse events. Commentators note the result would be non-significant with a 95% CI. They add that mature metastasis and clinical outcomes are needed, that an ARPI doublet with salvage RT remains unproven, and that FORMULA-509 was negative overall. Clinicians also caution against over-interpreting PSA. The debate is whether this early, loosely bounded signal justifies the added toxicity.

Key numbers: PFS HR 0.62 (80% CI 0.42–0.91) · Grade 3 AEs 19% vs 30%

Discussed by: @TylerSbrt, @TylerSbrt

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🔥 Top Ranked Tweets

Lauren Henke, MD, MSCI @lauren_henke

New #ASTRO2026 data from @NRGOnc /RTOG 0534 SPPORT 🔬🧬 presented by Shuang (George) Zhao @UTMDAnderson. PAM50 Luminal B = both prognostic & predictive of benefit from postop ADT.
📈 5-y FFP benefit: 31% vs 10% (p-int=.01)
🎯 10-y MFS: 20% vs -3% (p-int=.05)
#Pcsm @Astro_org https://t.co/BRJsYDWiQS

🔖 3 ❤️ 35 🔁 12 👁 3,715