(UroToday.com) The 2022 Annual Meeting of the American Urological Association (AUA) was host to The International Bladder Cancer Group (IBCG) AUA Bladder Cancer Forum which featured a case-based debate regarding the role of radical cystectomy in a patient who achieves a cT0 status after neoadjuvant chemotherapy. This session was moderated by Dr. Angela Smith, and Dr. Gary Steinberg was tasked with providing arguments in favor of radical cystectomy in this setting.
Dr. Smith began the debate with a case presentation of a 63-year-old relatively healthy male who was diagnosed with HG T2 bladder cancer. After being seen in a multidisciplinary clinic, decision was made to proceed with NAC followed by radical cystectomy. This patient received 4 cycles of ddMVAC with repeat imaging demonstrating no evidence of a bladder mass. The patient now asks if cystectomy is needed?
Dr. Steinberg began his argument in favor of radical cystectomy in this setting by presenting the following consideration:
- What are the overall treatment goals?
- What can the patient reasonably tolerate and thrive after?
- What treatment maximizes safety and efficacy?
- Is the bladder functional and worth saving?
We know that the goal of NAC is to treat occult microscopic metastasis, with a 5% absolute survival benefit. But does it downstage bulky tumor? The clinical staging of bladder cancer is highly inaccurate:
- At radical cystectomy, 41.9% of patients are upstaged and 5.9% are downstaged (Gray et al. 2014, Int J Radiat Oncol Biol Phys)
- At radical cystectomy, 32% are upstaged to non-organ confined stage (Turker et al. 2012, BJU Int)
- CT scanning accuracy to identify extravesical disease is only 35.4%
Dr. Steinberg next presented the preliminary results of the BladderPath study.1 As of 2021, 279 patients were registered and 113 randomized.
Preliminary report of the first 100 patients:
- 11 diagnosed with NMIBC using mpMRI
- 10 had NMIBC and 1 had MIBC confirmed by pathology
- 15 diagnosed with MIBC using mpMRI
- 10 were treated for presumed MIBC
- 5 underwent TURBT
- All 5 found to have NMIBC on pathology
If we defer radical cystectomy in these patients with presumed cT0 stage after NAC, then we are essentially surgically treating these patients with TURBT alone. Historical series by Whitmore et al. and Skinner et al. have demonstrated that 30-40% of tumors are downstaged by TUR. In the MDACC perioperative chemotherapy trial, 40% of cT2 patients were found to have pT2 disease with 61% of those upstaged to pT3b or pN+. Furthermore, we know that that re-staging TURBT detects residual disease in up to 76% of cases with ~28% of patients with pT1 upstaged to MIBC (49% if no muscle present in the initial specimen).
Dr. Steinberg next presented results from the SWOG 0219 trial of neoadjuvant Carboplatin/Paclitaxel/Gemcitabine in 74 patients.2 Of these 74 patients, 34 (46%) achieved a cT0 status, 24 of whom underwent cystoscopic surveillance and 10 underwent radical cystectomy, of whom 60% had residual disease with the following pathologic breakdown:
- pT2N2
- pT2aN0
- pT3aN0
- pT3bN0
- pT3a N0
- pT4aN1
The value of a “visibly complete” TURBT cannot be underestimated. Efstathiou et al. demonstrated in a matched cohort of 343 patients that a visibly complete TURBT was associated with significantly better DSS (68% versus 56%, p=0.03) and OS (57% versus 43%, p=0.003), although 42% of patients in the “TURBT not complete” group underwent radical cystectomy (22% in “TURBT complete”).
Multiple series have reported on the clinical and pathological staging discordancy of cystoscopy and cystectomy
In 2003, Sternberg et al. reported the outcomes of patients treated with neoadjuvant MVAC and TURBT alone.
Although at the current time, it appears that the evidence is in favor of proceeding with radical cystectomy despite a cT0 stage, it is important that we attempt to parse out a cohort that may benefit from more conservative surgical approaches as outlined by Dr. Steinberg below, where patients receiving 4 cycles of Nivolumab + Gemcitabine/Cisplatin achieved clinical CR rates of 48%.
When considering the risk benefit ratio, it is important to remember that MIBC is swiftly lethal, with 41% of untreated patients dying within 6 months of diagnosis and 80% within 2 years.
Dr. Steinberg concluded his talk as follows:
- Clinical staging with cystoscopy and CT/MRI do not correlate with pathological staging at cystectomy
- Currently, there are no randomized trial data to support the use of bladder-preserving strategies after neoadjuvant chemotherapy
- Patients refusing cystectomy after NAC are at risk of developing new invasive tumors in the bladder
- Delayed cystectomy salvages fewer than half of the patients relapsing with persistent or a new invasive bladder tumor
- Even aggressive TURBT of locally advanced bladder cancers after chemotherapy cannot reliably detect microscopic disease
Presented by:
Angela Smith, MD, MS, Associate Professor, Department of Urology, University of North Carolina, Chapel Hill, NC
Gary D. Steinberg, Professor and Director of the Goldstein Bladder Cancer Program at NYU Langone Health, New York, NY
Written by: Rashid Sayyid, MD, MSc – Urology Chief Resident, Augusta University/Medical College of Georgia, @rksayyid on Twitter during the 2022 American Urological Association (AUA) Annual Meeting, New Orleans, LA, Fri, May 13 – Mon, May 16, 2022.
References:
- Bryan RT, Liu Wenyu, Pirrie SJ, et al. Comparing an Imaging-guided Pathway with the Standard Pathway for Staging Muscle-invasive Bladder Cancer: Preliminary Data from the BladderPath Study. Eur Urol. 2021;80(1):12-15.
- deVere White RW, Lara Jr PN, Goldman B, et al. A sequential treatment approach to myoinvasive urothelial cancer: a phase II Southwest Oncology Group trial (S0219). J Urol. 2009;181(6):2476-80.