EAU 2017: Pure histological variants are associated with poor survival at radical cystectomy in patients with bladder cancer

London, England (UroToday.com) The importance of histologic variants outside of urothelial carcinoma within the realm of bladder tumor prognostics is well documented. Indeed, finding of variant histology, as in the case of micropapillary histology, can alter treatment decisions. In radical cystectomy (RC) series, divergent histology can account for up to 30% of cases, making it a relatively common occurrence. Its importance is demonstrated by the fact that the 4th edition of the WHO classification for urothelial carcinoma of the bladder takes into account variant histology, and dictates that pathologist should indicate the relative percentage of these variants in the pathology reports.

The authors of this study indicate that there is a dearth of data regarding “characteristics associated with histologic variants.” To that effect, they retrospectively assessed their own single-institution series of 1,067 patients treated with RC + pelvic lymph node dissection (PLND) between 1990 and 2013. The cohort was split into three groups based on final pathology: pure urothelial carcinoma, mixed variant / UC, and pure variant histology (based on RC specimen). Primary outcomes were recurrence, cancer-specific mortality (CSM) and overall mortality (OM). Besides patient factors, such as age, year of surgery, gender, Charlson comorbidity index (CCI), and pathologic features, such as pathologic stage, LVI, concomitant CIS, number of positive nodes and number of removed nodes, they also included the receipt of neoadjuvant chemotherapy or adjuvant chemotherapy as variables.

Of the entire cohort, 201 (19%) and 137 (13%) patients were found with mixed and pure variant at RC, respectively. In terms of presentation, patients with mixed histology predominantly had sarcomatoid, lymphoepitelial, squamous and glandular variants; patients with pure variant histology primarily had small cell or micropapillary variant.

Median follow-up for the cohort was 6.5 years, and the three groups had relatively similar distribution of age, gender, CCI, LNs removed and receipt of chemotherapy (adjuvant or neoadjuvant). In term of pathologic staging, however, the mixed variant cohort was more likely to be pT3+, have lymphovascular invasion and have positive surgical margins, even compared to the pure variant histology.

On multivariable logistic regression analysis, where pure urothelial carcinoma was the referent, pure variant histology patients had higher risk of recurrence, CSM and OM (HR 2.04, 1.48, and 1.40, respectively). Mixed histology did not harbor any significantly different risk than compared to pure UC.

The authors conclude that pathologic reporting of histologic variant is important due to the clinical sequelae of these findings. However, the data provided is not novel and has some flaws in statistical methodology. Specifically, comparison to original TURBT pathology would be ideal.

Limitations / Discussion Points:
1. While dedicated uropathologists were examining these specimens, there was no validation or assessment of inter-rater agreement.
2. Percent histologic variant (in the mixed histology samples) was not provided. Particularly based on recent WHO guidelines, this would have been helpful in teasing out differences in this heterogeneous group.
3. Using radical cystectomy pathologic is appropriate, but often, clinical decisions are made on TURBT pathology – correlated to original TURBT pathology would strengthen the analysis. Prior studies have demonstrated mixed concordance between pathology findings.
4. The quality of the MV analysis is questionable for a few reasons. NAC does not demonstrate any benefit, while adjuvant therapy is associated with higher rates of recurrence – conflicting with Level 1 evidence. Additionally, the use of year of diagnosis as a continuous variable is statistically inappropriate – it would have been better to use it as a categorical variable or eras.

Presented by: Khorrami M.H. (not present, did not present poster)

C0-Authors: Colombo R., Gandaglia G., Di Trapani E., Burgio G., Damiano R., Mattei A., Shariat S., Salonia A., Briganti A., Montorsi F., Gallina A.

1. IRCCS Ospedale San Raffaele, Dept. of Urology, Milan, Italy
2. Magna Graecia University of Catanzaro, Dept. of Urology, Catanzaro, Italy
3. Luzerner Kantonsspital, Dept. of Urology, Lucerne, Switzerland
4. Medical University of Vienna, Dept. of Urology, Vienna, Austria

Written by: Thenappan Chandrasekar , Clinical Fellow, University of Toronto
Twitter: @tchandra_uromd

at the #EAU17 -March 24-28, 2017- London, England