(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. Mario Fernandez was tasked with providing support to the argument that presence of variant histology should change the management of bladder cancer patients.
Dr. Black began the session by distinguishing between the definitions of non-urothelial bladder cancer (squamous, adenocarcinoma, sarcoma, lymphoma, melanoma etc.) and variants of urothelial carcinoma (squamous differentiation, glandular differentiation, micropapillary, sarcomatoid, plasmacytoid, nested, etc.). The main question remains: Do histologic variants reflect biologic differences that require tailored treatment? He presented a case scenario of a 64-year-old female with metabolic syndrome presenting with asymptomatic gross hematuria and found to have a 2 cm high grade T1 urothelial carcinoma with 25% micropapillary differentiation.
Dr. Fernandez began his discussion by referencing the AUA, NCCN, and EAU guidelines recommendation regarding the management of variant histologies in non-muscle invasive bladder cancer. They are all based on expert opinion due to the lack of high-quality evidence and all support a more aggressive approach, specifically in the form of early radical cystectomy (AUA, EAU). It has been well-established that micropapillary bladder cancer is a more aggressive disease, with a median overall survival nearly half that of conventional bladder cancer (44.7 versus 91.9 months, p<0.0001), and presence of this variant is an independent predictor of death.
This is even true in the clinically non-muscle invasive disease spectrum, whereby patients with T1 micropapillary bladder cancer have high rates of lymph node metastasis development (35%), upstaging at immediate RC (23-73%), and five-year cancer-specific mortality rates (13-40%). Moreover, 45-50% of variant histology cases are missed by community pathologists, with the lowest concordance rate of variant histology being present for micropapillary bladder cancer.
A retrospective report from MD Anderson of 72 patients with T1 micropapillary bladder cancer, all confirmed by a genitourinary pathologist, demonstrated that upfront cystectomy is associated with significantly superior 5 year disease specific survival rates of 100% with upfront cystectomy versus 60% with primary BCG and 62% even in those with delayed cystectomy. This was an early signal that such patients would likely benefit from early, aggressive surgical treatment.
Next, prognostic factors in the form of extent of micropapillary involvement (25 or 100%) and presence of lymphovascular invasion (LVI) demonstrated that patients with extensive micropapillary involvement had a significantly worse 5-year disease specific survival of 42% versus 73% (focal)1. Presence of LVI in patients with T1 micropapillary disease was shown to be an adverse prognostic feature in a European, multicenter cohort.2 Similarly, results from a UK cohort demonstrated that such patients with pure micropapillary disease or LVI had significantly worse progression-free survival.3
Dr. Fernandez concluded his talk as follows with regards to T1 micropapillary bladder cancer
- An uncertainty of adequate detection and classification remains
- Evidence is limited and conflicting
- Optimal approach remains controversial
- There is a need for reliable predictive tools in the form of biomarkers
- In the meantime, choose the safest oncologic option
- Immediate radical cystectomy
- Same message for plasmacytoid and sarcomatoid variants
Presented by: Mario I. Fernandez, MD, Professor of Urology, Faculty of Medicine Clinica Alemana-Universidad del Desarrollo
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:
- Willis DL, Fernandez MI, Kamat AM, et al. Clinical outcomes of cT1 micropapillary bladder cancer. J Urol. 2015;193(3):11239-34.
- Lonati C, Baumeister P, Afferi L, et al. Survival Outcomes After Immediate Radical Cystectomy Versus Conservative Management with Bacillus Calmette-Guérin Among T1 High-grade Micropapillary Bladder Cancer Patients: Results from a Multicentre Collaboration. Eur Urol Focus. 2021;18;S2405-4569(21)00195-5.
- Jackson BL, Mohamad Aza, Mayer N, et al. Is Immediate Radical Cystectomy Necessary for All Patients with Non-Muscle-Invasive Micropapillary Bladder Cancer? Urol Int/ 2016;96(1):32-8.