(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 about the significance of variant histology on changes in the management of bladder cancer patients. This session was moderated by Dr. Peter Black, and Dr. Michael O’Donnell was tasked with providing an argument to the debate presence of variant histology should change the management of bladder cancer patients.
Dr. O’Donnell began his presentation by highlighting the difficulties in assessing treatment response in micropapillary non-muscle invasive bladder cancer (NMIBC):
- It is a rare cancer (~0.15% of all NMIBC cases in the NCDB)
- Often missed by community pathologists (45-50%)
- Even among experts, there is no consensus in strict criteria for determining micropapillary carcinoma (Black, Transl Ca Res, 2020)
- Early studies may have been biased by more extreme cases secondary to referral patterns and case-finding bias
- No randomized trial exists to accurately assess comparative outcomes
- Nuance-driven subtleties may affect outcomes
- Re-resection
- Percentage of micropapillary component
- Mucosal versus invasive micropapillary component
- Presence of carcinoma in situ
- T1 substaging
- Presence/absence of lymphovascular invasion (LVI)
- Genomic classifiers suggesting heterogeneity
Certain histologic subtleties have been shown to affect outcomes:
- Very important:
- Percent of micropapillary disease
- Progression rates of 69% with extensive versus 31% with focal involvement in the MDACC cohort
- Progression HR of 2.5 for pure versus mixed disease (Lonati 2021)
- Higher percentage involvement associated with worse outcomes (Gaya, Can J Urol 2010)
- Presence of LVI:
- Correlates with overall survival rates and presence of positive lymph nodes (Jackson 2016) and disease progression with a HR of 2.4 (Lonati 2021)
- Percent of micropapillary disease
- Possibly Important:
- T1 re-resection
- 5-year disease-specific survival of 75% with BCG versus 82% with radical cystectomy (MSKCC-Spaliviero, J Urol 2014)
- Selective re-resection in 1/3 of patients was associated with similar disease-specific and overall survival for patients undergoing BCG versus radical cystectomy
- Mucosal versus invasive micropapillary component
- Median OS of 63 versus 47 months (Jackson, Urol Int 2016)
- T1 re-resection
- Not important:
- Size
- T1a versus T1b
- Presence or absence of carcinoma in situ
Similar to Dr. Fernandez, Dr. O’Donnell highlighted the recent report by Lonati et. al in Eur Urol Focus, whereby patients with mixed histology and no LVI had significantly better recurrence-free and progression-free survival compared to patients with pure micropapillary disease or LVI.1
Next, Dr. O’Donnell presented results of three large retrospective comparative series strongly supporting selective bladder preservation in patients with micropapillary disease.
Sui et al. presented results from the National Cancer Database (NCDB) that demonstrated non-significantly different overall survival rates in 869 patients treated with bladder preserving surgery versus radical cystectomy. These results were supported by a more recent report from the NCDB database that demonstrated significantly superior 5-year overall survival in patients managed with bladder preservation versus radical cystectomy (53% versus 44%, HR 1.45, p<0.001). Of note in this same study, radical cystectomy was noted to be superior for the other urothelial carcinoma variants of small cell (31% versus 22%), squamous (40% versus 20%), glandular (44% versus 41%) and sarcomatoid disease (32% versus 23%). Although Lonati et al. demonstrated that pure micropapillary disease or LVI is associated with worse outcomes than mixed variant histology, the cancer-specific and overall mortality rates did not differ in patients treated with immediate radical cystectomy versus conservative treatment.
Dr. O’Donnell concluded his talk by presenting intriguing preliminary results of Gem/Doce and Val/Doce for high-grade, non-muscle invasive micropapillary bladder cancer from the University of Iowa.
- 8 patients – all first time presentation with no prior therapy
- 1 HG Ta with micropapillary features
- 4 HG T1 with micropapillary(minute, minor, 1%, 25%)
- 3 HG T1 + CIS with micropapillary(“features”, mixed, 30%)
- All negative for micropapillary disease with re-resection
- 6/8 (75%) have had a durable complete response to Gem/Doce with the remaining 2/8 with immediate failure having no micropapillary features
- The 2/8 (25%) were retreated with Val/Doce Durable complete response (24, 27 months)
- All patients are alive with bladder in situ at median survival of 29 months (14-42)
- All patients have had normal CT scan and normal FISH analysis within the last 3-6 months
Presented by: Michael O’Donnell, MD, Professor, Department of Urology, University of Iowa, Iowa City, IA
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.
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