📬 GU Oncology Intelligence Digest — Week 2026-W33

FDA approval and Lancet publication of PSMAddition bring Lu-177-PSMA-617 into frontline PSMA-positive metastatic hormone-sensitive prostate cancer, alongside TALAPRO-3 in NEJM, capivasertib approval in PTEN-deficient disease, INDIBLADE bladder preservation, new IBCG bladder biomarker consensus and a PSA nadir meta-analysis.

⚡ TL;DR

📄 Publications

[177Lu]Lu-PSMA-617 in patients with PSMA-positive metastatic androgen pathway modulator-naive/sensitive prostate cancer (PSMAddition): a phase 3 randomised, controlled trial. — 1144 patients randomised 1:1 (n=572 per arm), 779 (68%) with high-volume disease
Impact of PSA Nadir on Outcomes in Metastatic Hormone-Sensitive Prostate Cancer: A Systematic Review and Reconstructed Individual Patient Data Meta-analysis. — 8 studies included, 1638 patients for the OS analysis and 1104 for the PFS analysis

🐦 Twitter / 🦋 Bluesky

USPCC26 point-counterpoint: is PSMA PET ready to define progression and treatment response? — Proponents cite RECIP 1.0 standardized response criteria and early PSMA response at about 3 months being prognostic in mCRPC, with RECIP progressive disease versus non-progression giving HR 2.6 for overall survival
Clinical and genomic determinants of extraordinary versus poor response to ADT/ARPI in metastatic prostate cancer — A Duke-led manuscript reports clinical and genetic predictors of extraordinary and poor responses to ADT/ARPI therapy in metastatic androgen pathway modulator-sensitive prostate cancer
PSA nadir at or below 0.2 ng/mL separates dramatically different survival in metastatic hormone-sensitive prostate cancer — PSA nadir <=0.2 ng/mL was associated with OS 92.8 vs 34 months (HR 0.27) and PFS not reached vs 12.1 months (HR 0.19)

Full details below ↓

📄 What's Being Published

Manuscripts:

Systemic Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer: ASCO Living Guideline, Version 2026.1.4. — Taplin Mary-Ellen et al., J Clin Oncol

The ASCO living guideline for metastatic castration-resistant prostate cancer is maintained by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in the ASCO Guidelines Methodology Manual. Updates are issued on a regular schedule rather than as discrete fixed editions.

Clinical bottom line: The ASCO living guideline for metastatic castration-resistant prostate cancer is refreshed on a continuous schedule rather than in fixed editions, so clinicians should check the current version rather than a static document.

Read full article →

[177Lu]Lu-PSMA-617 in patients with PSMA-positive metastatic androgen pathway modulator-naive/sensitive prostate cancer (PSMAddition): a phase 3 randomised, controlled trial. — Tagawa Scott T et al., Lancet

PSMAddition randomised 1,144 patients 1:1 (n=572 per arm), of whom 779 (68%) had high-volume disease; radiographic progression-free survival was significantly improved in the Lu-177-PSMA-617 arm, with a 28% reduction in the relative risk of radiographic progression or death (HR 0.72, 95% CI 0.58–0.90; p=0.0021), with median radiographic progression-free survival not reached in either arm. Grade 3 or worse adverse events occurred in 286 (51%) of 564 patients in the Lu-177-PSMA-617 arm versus 243 (43%) of 565 patients in the control arm; dry mouth was the most common adverse event, affecting 258 (46%) versus 21 (4%), and all cases were grade 1 or 2.

Clinical bottom line: The full PSMAddition publication in the Lancet supplies the primary data behind the FDA approval, showing Lu-177-PSMA-617 added to ADT plus an ARPI prolongs radiographic progression-free survival in PSMA-positive metastatic hormone-sensitive prostate cancer at the cost of more grade 3+ toxicity and dry mouth, with overall survival still immature.

Read full article →

Impact of PSA Nadir on Outcomes in Metastatic Hormone-Sensitive Prostate Cancer: A Systematic Review and Reconstructed Individual Patient Data Meta-analysis. — Di Civita Mattia Alberto et al., Target Oncol

This meta-analysis pooled 8 studies comprising 1,638 patients for the overall survival analysis and 1,104 for the progression-free survival analysis; patients achieving a PSA nadir ≤0.2 ng/mL had a median OS of 92.8 months versus 34 months for those with a nadir >0.2 (HR 0.27, 95% CI 0.22–0.33, p<0.0001). Median PFS was not reached versus 12.1 months in favour of the ≤0.2 group (HR 0.19, 95% CI 0.16–0.23, p<0.0001).

Clinical bottom line: A PSA nadir at or below 0.2 ng/mL on ARPI or docetaxel identifies metastatic hormone-sensitive prostate cancer patients with dramatically better survival and should be used as an early efficacy checkpoint.

Read full article →

🔗 Also discussed on social media →

Mathematical Biomarkers of Adaptive Therapy Outcomes in Prostate Cancer. — Gallagher Kit et al., JAMA Oncol

This retrospective modelling and validation study used data from two independent cohorts: 40 patients with castrate-sensitive prostate cancer and 13 patients with metastatic castrate-resistant prostate cancer. In the castrate-sensitive cohort, the adaptive therapy score derived from first-cycle data was highly prognostic for prolonged time to progression (HR 0.49; 95% CI 0.31–0.76; P=.002); in the metastatic castrate-resistant cohort, the score exhibited a strong rank correlation with clinical time to progression (Spearman rho=0.76; P=.002).

Clinical bottom line: Mechanism-based mathematical biomarkers from first-cycle PSA kinetics outperformed conventional PSA metrics for predicting time to progression and survival under adaptive therapy, offering a concrete way to personalise treatment-break scheduling.

Read full article →

🗣️ 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).

USPCC26 point-counterpoint: is PSMA PET ready to define progression and treatment response?

Proponents of PSMA PET-defined progression cited RECIP 1.0 standardised response criteria and early PSMA response at approximately 3 months being prognostic in metastatic castration-resistant prostate cancer, with RECIP progressive disease versus non-progression yielding an HR of 2.6 for overall survival; they further noted that in an EMBARK-eligible cohort with negative conventional imaging, 84% were PSMA PET positive and 46% had M1 disease. Opponents countered that PSMA expression is dynamically regulated by the androgen axis—meaning ADT and ARPIs can alter uptake independent of true tumour burden—and that quantitative metrics show meaningful test-retest variability with inconsistent lesion segmentation. A central objection was that metastasis-free survival was validated as an overall survival surrogate using CT and bone scan, not PSMA PET, and that PSMA-defined progression lacks prospective overall survival validation, with ARASTEP ongoing. The core debate: should a PSMA PET-only lesion in a patient with negative conventional imaging count as progression and trigger a change in therapy?

Discussed by: @urotoday, @urotoday, @urotoday, @urotoday

→ View representative tweet

Clinical and genomic determinants of extraordinary versus poor response to ADT/ARPI in metastatic prostate cancer

A Duke-led manuscript reported clinical and genetic predictors of extraordinary and poor responses to ADT/ARPI therapy in metastatic androgen pathway modulator-sensitive prostate cancer. In a real-world cohort, favourable features such as low-volume disease, better performance status, and normal laboratory markers predicted improved outcomes, while alterations in genes including TP53 and MYC were linked to poorer survival. The authors framed the work as directly relevant to recent approvals, posing the question of who needs intensification and which strategy best fits the biology. The debate centres on whether clinical features plus TP53 and MYC status can identify the metastatic hormone-sensitive prostate cancer patients who can safely remain on ADT plus ARPI alone rather than adding a third agent.

Discussed by: @neerajaiims, @DCockrellMD, @OncoAlert

→ View representative tweet

PSA nadir at or below 0.2 ng/mL separates dramatically different survival in metastatic hormone-sensitive prostate cancer

A reconstructed individual patient data meta-analysis of 8 studies—1,638 patients for the overall survival analysis and 1,104 for the progression-free survival analysis—found that a PSA nadir ≤0.2 ng/mL was associated with a median OS of 92.8 versus 34 months (HR 0.27) and a median PFS of not reached versus 12.1 months (HR 0.19). Concurrent modelling work showed that first-cycle PSA kinetics predicted time to progression and overall survival better than standard PSA metrics in patients receiving adaptive therapy. The unresolved clinical question is whether failure to reach a PSA nadir of 0.2 ng/mL should trigger treatment escalation in metastatic hormone-sensitive prostate cancer, or whether it marks prognosis alone without a mandate to act.

Discussed by: @g_procopio_, @JAMAOnc

→ View representative tweet

🔥 Top Ranked Tweets

Elad Sharon @EladSharonMD

RT @DrChoueiri: JUST IN: @US_FDA approves LuPSMA (Pluvicto, @Novartis) in combination with androgen receptor pathway inhibitor (ARPI) in PSMA (+) metastatic hormone-sensitive prostate cancer. Approval based on PSMAddition trial (HR PFS 0.72), immature OS. https://t.co/w3sa2QNBUc

🔖 31 ❤️ 110 🔁 46 👁 7,030