Predictors of Complete Pathologic Response (pT0) to Neoadjuvant Chemotherapy in Muscle-invasive Bladder Carcinoma.
No predictors of a complete pathologic response (pT0) to neoadjuvant chemotherapy (NAC) in muscle-invasive bladder carcinoma have been established. We performed a retrospective analysis of 50 patients to identify potential predictors. Our results showed that the presence of additional transitional cell variants on pathologic examination (mixed tumors) predicted against pT0, suggesting the avoidance of NAC and its morbidity in these patients with mixed tumors.


BACKGROUND
Randomized trials have supported the use of cisplatin-based neoadjuvant chemotherapy (NAC) in muscle-invasive bladder carcinoma (MIBC) owing to the survival advantage, which has correlated with downstaging of the cancer to pT0. Only 30% to 40% of patients receiving NAC have attained a pT0 response at cystectomy; the remaining have either residual disease or progression. We aimed to identify the factors that could predict a pT0 response to NAC.


METHODS
Of 336 patients who had undergone robotic cystectomy at our institute from May 2007 to March 2014, we identified 50 patients who had undergone NAC for MIBC. We conducted a retrospective study, dividing these 50 patients into 2 groups, those with and without a pT0. Factors, including age, histologic features, hydronephrosis at initial presentation, and chemotherapy type, were examined by both univariate and multivariate logistic regression analysis.


RESULTS
Of the 50 patients, 14 (28%) had pT0 at cystectomy, 20 (40%) had progressive disease, and 16 (32%) had residual disease. The median age was 67.5 years, the median glomerular filtration rate at presentation was 87.5 mL/min, the patients had undergone a median of 3 NAC cycles, and the median time from the end of chemotherapy to surgery was 4 weeks. The odds of a pT0 response for pure urothelial carcinoma (UC) were approximately 11 times greater relative to cancers with transitional cell variant histologic features or mixed tumors (odds ratio 0.09, 95% confidence interval 0.021-0.380; P = .0011), including squamous, glandular differentiation, small cell, micropapillary, sarcomatoid, nested component, lymphoepithelioma-like, and plasmacytoid variants.


CONCLUSIONS
The presence of pure UC favored a pT0 response to NAC compared with those with variant histologic features or mixed tumors. These potential predictors warrant prospective validation to allow the ideal selection of patients for NAC.
Department of Medical Oncology, Roswell Park Cancer Institute, Buffalo, NY. Electronic address: pvkiran7@gmail.com.
Venkata K
VK
Pokuri
Department of Urologic Oncology, Roswell Park Cancer Institute, Buffalo, NY.
Johar R
JR
Syed
Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY.
Zhengyu
Z
Yang
Department of Urologic Oncology, Roswell Park Cancer Institute, Buffalo, NY.
Erinn P
EP
Field
Department of Pathology, Case Western Reserve University, Cleveland, OH.
Susanna
S
Cyriac
Department of Medical Oncology, Indiana University Simon Cancer Center, Indianapolis, IN.
Roberto
R
Pili
Department of Medical Oncology, Roswell Park Cancer Institute, Buffalo, NY.
Ellis Glenn
EG
Levine
Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY.
Gissou
G
Azabdaftari
Department of Medical Oncology, Inova Comprehensive Cancer Research Institute, Falls Church, VA.
Donald L
DL
Trump
Department of Urologic Oncology, Roswell Park Cancer Institute, Buffalo, NY.
Khurshid
K
Guru
Department of Medical Oncology, Roswell Park Cancer Institute, Buffalo, NY.
Saby
S
George
D000368:Aged; D000369:Aged, 80 and over; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D015653:Cystectomy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
Complete pathological response; Mixed tumors; Muscle-invasive; Neo-adjuvant chemotherapy; Predictors; Urothelial carcinoma; Variant histology