Multicenter Validation of Histopathologic Tumor Regression Grade After Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Carcinoma.

Voskuilen, Charlotte S; Oo, Htoo Zarni; Genitsch Gratwohl, Vera; Smit, Laura A; Vidal, Alvaro; Meneses, Manuel; Necchi, Andrea; Colecchia, Maurizio; Xylinas, Evanguelos; Fontugne, Jacqueline; Sibony, Mathilde; Rouprêt, Morgan; Lenfant, Louis; Côté, Jean-François; Buser, Lorenz; Saba, Karim; Furrer, Marc A.; van der Heijden, Michiel S; Daugaard, Mads; Black, Peter C; ... (2019). Multicenter Validation of Histopathologic Tumor Regression Grade After Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Carcinoma. The American journal of surgical pathology, 43(12), pp. 1600-1610. Lippincott Williams & Wilkins 10.1097/PAS.0000000000001371

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Response classification after neoadjuvant chemotherapy in muscle-invasive bladder carcinoma is based on the TNM stage at radical cystectomy. We recently showed that histopathologic tumor regression grades (TRGs) add prognostic information to TNM. Our aim was to validate the prognostic significance of TRG in muscle-invasive bladder cancer in a multicenter setting. We enrolled 389 patients who underwent cisplatin-based chemotherapy before radical cystectomy in 8 centers between 2010 and 2016. Median follow-up was 2.2 years. TRG was determined in radical cystectomy specimens by local pathologists. Central pathology review was conducted in 20% of cases, which were randomly selected. The major response was defined as ≤pT1N0. The remaining patients were grouped into partial responders (≥ypT2N0-3 and TRG 2) and nonresponders (≥ypT2N0-3 and TRG 3). TRG was successfully determined in all cases, and interobserver agreement in central pathology review was high (κ=0.83). After combining TRG and TNM, 47%, 15%, and 38% of patients were major, partial, and nonresponders, respectively. Combination of TRG and TNM showed significant prognostic discrimination of overall survival (major responder: reference; partial responder: hazard ratio 3.5 [95% confidence interval: 1.8-6.8]; nonresponder: hazard ratio 6.1 [95% confidence interval: 3.6-10.3]). This discrimination was superior compared with TNM staging alone, supported by 2 goodness-of-fit criteria (P=0.041). TRG is a simple, reproducible histopathologic measurement of response to neoadjuvant chemotherapy in muscle-invasive bladder cancer. Integrating TRG with TNM staging resulted in significantly better prognostic stratification than TNM staging alone.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology

UniBE Contributor:

Genitsch Gratwohl, Vera; Furrer, Marc and Seiler, Roland

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1532-0979

Publisher:

Lippincott Williams & Wilkins

Language:

English

Submitter:

Vera Genitsch Gratwohl

Date Deposited:

13 Nov 2019 09:45

Last Modified:

14 Nov 2019 01:33

Publisher DOI:

10.1097/PAS.0000000000001371

PubMed ID:

31524642

BORIS DOI:

10.7892/boris.134694

URI:

https://boris.unibe.ch/id/eprint/134694

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