EAU 2021: Rapid-Fire Debate: Optimal Therapy for Patient with T0 After Neoadjuvant Chemotherapy

(UroToday.com) The 2021 European Association of Urology (EAU) annual meeting had a Controversies in Bladder Cancer 2021: Rapid-fire debates session. The session was introduced by Dr. Ashish Kamat with chairs of the session, Professors Joan Palou and Arnulf Stenzl. There were five rapid-fire debates with case-based discussions, multiple presenters have the opportunity to discuss nuances of common dilemmas facing urologic oncology patients and providers and to use these evidence-based debates to provide clear, rational guidance on the timely management of difficult situations in bladder cancer.

In this rapid-fire debate, the focus is on the optimal therapy for patients with cT0 disease after neoadjuvant chemotherapy. We have three debaters for this talk – Dr. Kamal Pohar arguing for cystectomy, Dr. Ananya Choudhury arguing for trimodal therapy, and Dr. Paolo Gontero arguing for observation/bladder sparing.

Case: This is a 65 -year-old man who presents with gross hematuria while exercising. PMH significant for hypertension and ankle surgery. Has a remote smoking history. eGFR 67.

Cytology positive.
CT Chest/Urogram – normal upper tracts. +dome tumor. No LAD. Normal chest imaging.
Underwent transurethral resection of bladder tumor (TURBT) – completely resected 4 cm tumor at the dome. Bladder biopsies x 6 (negative for malignancy). EUA – mobile bladder.
Pathology – HG muscle invasive bladder cancer (MIBC), +LVI.
He plans for neoadjuvant chemotherapy (NAC) and surgery. Completes NAC but then gets cold feet about surgery.
CT A/P after cycle 4 – normal upper tracts, mild dome thickening.
Repeat TURBT – no residual disease, scar, and inflammation only.
Cytology negative.

Dr. Pohar provided a convincing argument for proceeding with surgery. Below I highlight the main points from his discussion.

1. cT0 is a misnomer – multiple studies have demonstrated that our current diagnostic tools are not adequate at appropriately identifying pT0 status.

Becker et al.¹ – only 47% of patients who were cT0 post-NAC restaging were pT0 on final pathology. 27% had invasive disease. 21 patients with normal cystoscopy after NAC – 38% had invasive histology at cystectomy.

2. cT0 after NAC natural history – in the few studies that do look at outcomes of patients who opt against cystectomy or undergo trimodal therapy (unselected), the outcomes are poor.

45-70% bladder recurrence. 11-40% MIBC. High rate of disease specific mortality.
20-50% end up requiring salvage cystectomy

3. Nodal understaging post-NAC is common

He notes that current imaging is not ideal for nodal disease, as indicated by node positivity rates for cN0 MIBC undergoing cystectomy - ~20-40% are node positive at the time of cystectomy.

4. Untreated field effect: CIS

collaborative review statement² of experts note that the presence of CIS should exclude patients from trimodal therapy (TMT).
He also notes that ~30% of patients with known CIS still have CIS after cystectomy; but 26% of patients are found to have CIS on final cystectomy pathology.

For these reasons, and per guidelines, he recommends proceeding with cystectomy.

Dr. Choudhury as the radiation oncologist on the panel argued for TMT. She highlighted the work out of Toronto (Kulkarni et al.³) and MGH prospective cohorts, as well as retrospective series and meta-analyses to highlight the fact that TMT patients can do as well as surgically treated patients. The caveat for the prospective series is that these are well selected patients.

She notes that QOL outcomes are similar between surgery and radiation in most parameters – except for male-related sexual QOL, where radiation fares much better.

As for late toxicity, which is often used to argue against XRT, she notes that more recent series have demonstrated good toxicity profiles in patients undergoing TMT.

Ultimately, though, she agrees with Dr. Pohar that some consolidative local therapy is needed.

Dr. Gontero had the unfortunate position of defending observation alone, which it wasn’t clear that he himself supported.

He showed the results of a few institutional series of surveillance following NAC and evidence of cT0 status – mostly single institution series with relatively short follow-up (2-4.5 years). However, approximately 65-75% of patients kept their bladders and the reported CSS ranged from 71-90%, which is not that different from NAC+RC series.

When it comes to salvage radical cystectomy in the patients who do have a recurrence of MIBC, he notes that those same series noted salvage RC rates between 18-28%. Up to 50% of the patients had local recurrence, mostly NMIBC. Only 10% of the cancer-specific deaths were attributed to delayed RC.

Ultimately, he notes that patient selection is key – you should avoid in patients with hydronephrosis, mutifocal CIS, large tumors. They require strict follow-up – but most recurrences with be NMIBC.

In the end, most panelists agree the data isn’t strong for observation and ongoing trials (with genomic/genetic markers to select for better outcomes) may change that.

Presented by:
Sima Porten, MD, MPH, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA
Kamal S Pohar, MD, Ohio State University Comprehensive Cancer Center, Columbus, OH
Ananya Choudhury, MA, PhD, University of ManchesterManchester, UK
Paolo Gontero, MD, University of Torino School of MedicineTurin, Italy

Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Assistant Professor of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, @tchandra_uromd on Twitter during the 2021 European Association of Urology, EAU 2021- Virtual Meeting, July 8-12, 2021.

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