Downstaging and Survival Outcomes Associated With Neoadjuvant Chemotherapy Regimens Among Patients Treated With Cystectomy for Muscle-Invasive Bladder Cancer

Peyton, Charles C.; Tang, Dominic H.; Reich, Richard R.; Azizi, Mounsif; Chipollini, Juan; Pow‐Sang, Julio M.; Manley, Brandon; Spiess, Philippe E.; Poch, Michael; Sexton, Wade J.; Fishman, Mayer; Zhang, Jingsong; Gilbert, Scott M.

doi:10.1001/jamaoncol.2018.3542

Cited by 116 publications

(79 citation statements)

References 40 publications

(63 reference statements)

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“…This study has several limitations derived from its retrospective nature and not being a clinical trial, including the relatively long recruitment period and modest sample size, lack of centralized pathology review, inclusion of patients treated with carboplatin, and possible uncontrolled differences in clinical management. These limitations have been mitigated through several types of analyses and they reflect much of the variability associated with the application of NAC in clinical practice (33,34). While the P-values found are close to the threshold of significance, the OR are in the range of clinical relevance.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemistry-based taxonomical classification of bladder cancer predicts response to neoadjuvant chemotherapy

Font¹,

Domènech

Benítez

et al. 2019

Preprint

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Platinum-based neoadjuvant chemotherapy (NAC) increases the survival of patients with organ-confined urothelial bladder cancer (UBC). Because not all patients benefit from treatment, NAC has not been widely applied in the clinical setting. There is strong evidence, based on retrospective studies, that patients with Basal/Squamous (BASQ)-like tumours present with more advanced disease and have worse prognosis; global transcriptomics can identify tumour subtypes associated with response to NAC. We aimed to investigate whether tumour immunohistochemical (IHC) subtyping predicts NAC response. Patients with muscle-invasive UBC having received platinum-based NAC were identified in two hospitals in Spain. Tissue microarrays were constructed; RNA and DNA were extracted from full sections. Nanostring analysis and immunohistochemistry to identify BASQ-like tumours and mutational analysis of UBC oncogenes. We used hierarchical clustering to classify 126 tumours and adjusted logistic regression to assess association with treatment response. Outcomes were progression-free survival and disease-specific survival; univariable and multivariate Cox regression models were applied. We found very high concordance between mRNA and protein for the 4 markers analyzed. We identified three main subgroups: BASQ-like (FOXA1/GATA3 low; KRT5/6/14 high), Luminal-like (FOXA1/GATA3 high; KRT5/6/14 low), and mixed-cluster (FOXA1/GATA3 high; KRT5/6 high; KRT14 low). Patients with BASQ-like tumours were more likely to achieve a pathological response to NAC, displaying a disease-specific survival similar to that of the remaining patients. In conclusion, patients with BASQ-like tumours - identified through simple and robust immunohistochemistry - have a higher likelihood of undergoing a pathological complete response to NAC. Prospective validation in independent series is required.Novelty and impactNeoadjuvant chemotherapy is an important component of the management of patietns with muscle-invasive bladder cancer but improved stratification is necessary. This retrospective study shows that patients with BASQ-like tumors can be identified using immunohistochemistry on paraffin-embedded tissue and are 4-fold more likely to achieve a pathological complete response to platinum-based NAC. The disease-specific survival of patients with BASQ-like tumours treated with NAC was not different from that of other tumour subtypes.

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Section: Discussionmentioning

confidence: 99%

Immunohistochemistry-based taxonomical classification of bladder cancer predicts response to neoadjuvant chemotherapy

Font¹,

Domènech

Benítez

et al. 2019

Preprint

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“…Similar superiority was shown in terms of pathological complete response (pCR; ypT0pN0) with 41.3%, 24.5%, and 9.4%, respectively. However, the difference in OS did not reach statistical significance [13].…”

Section: Muscle-invasive Urothelial Bladder Cancermentioning

confidence: 88%

Neoadjuvant therapy in urothelial cancer

Brönimann

D’Andrea

Shariat

et al. 2019

memo

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Neoadjuvant cisplatin-based chemotherapy is standard treatment for muscle-invasive bladder cancer before radical cystectomy (RC). Despite level 1 evidence demonstrating an overall survival benefit for patients undergoing RC after neoadjuvant chemotherapy (NAC), acceptance rates are still low. In high-risk upper tract urothelial cancer (UTUC), cumulative evidence suggests that NAC for locally advanced UTUC can improve oncological outcome. Ongoing phase 3 trials will finally prove the benefit or futility of NAC in this tumor entity. Since urothelial cancer (UC) is a heterogeneous disease, predictive biomarkers are needed to select specific patient populations and potentially increase response rates to NAC. Novel targeting therapies, including immune checkpoint inhibitors, have been approved for metastatic UC. In combination with predictive biomarkers, these might have the potential to change systemic therapy for UC from a "one-fits-all" principle to a more individualized approach.

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“…In most studies, downstaging had an important impact on survival, even neoadjuvant chemotherapy was not performed 4,6,20 . In this study, complete TURBT was related to a higher rate of downstaging, which was from T2/T1 to T1/Ta, and downstaging was not signi cantly associated with oncological outcome signi cantly.…”

Section: Commentsmentioning

confidence: 99%

“…Radical cystectomy (RC) is the standard option for muscle invasive bladder cancer (MIBC) and some high-risk non-muscle invasive bladder cancer (NMIBC). For locally-advanced disease, neoadjuvant chemotherapy is recommended, and downstaging is associated with good prognosis [4][5][6][7][8][9] . For ≤ pT2N0M0 disease, complete TURBT was related to a higher rate of downstaging after RC, and it was associated with good outcomes [10][11][12][13] .…”

Section: Introductionmentioning

confidence: 99%

The role of complete TURBT before radical cystectomy for organ-confined bladder cancer

Heng

Chen

Zhou

et al. 2020

Preprint

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ObjectiveTo investigate the role of complete transurethral resection of bladder tumor (TURBT) before radical cystectomy.Patients and MethodsPatients who underwent radical cystectomy in our center from January 2008 to December 2018 were retrospectively reviewed. Those with disease >T2N0M0 or positive surgical margin and those who were administrated neoadjuvant/adjuvant chemotherapy or radiotherapy were excluded. Complete TURBT was defined as no visible lesion under endoscopic examination after TURBT, presence of muscle layer in the specimen or no tumor in a specimen separated from the base. Kaplan–Meier and log-rank tests assessed disease-free survival. Logistic and Cox regression analysis were performed to identify potential predictors.ResultsIn total, 236 patients were included, and 207 patients were male. The median age was 61 years old. The median number and size were 1 and 3cm respectively, and maximal pathological T stage was T2 in 94 patients. Complete TURBT was related to tumor size (p=0.041), histological variants (p=0.026) and downstaging (p<0.001). Tumor size, grade and histological variants were independent predictors of complete TURBT. With a median follow-up of 42.7 months, 30 patients experienced recurrence. Age and histological variants were independent predictors of disease-free survival (p=0.027 and 0.041, respectively). Complete TURBT was associated with poor prognosis, however, the result was not significant (p=0.068). Downstaging was not associated with survival outcome.ConclusionsComplete TURBT is related to an increased rate of downstaging before radical cystectomy, and both of these factors did not improve oncological outcomes for patients with organ-confined bladder cancer.

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Downstaging and Survival Outcomes Associated With Neoadjuvant Chemotherapy Regimens Among Patients Treated With Cystectomy for Muscle-Invasive Bladder Cancer

Abstract: This study suggest that neoadjuvant ddMVAC followed by cystectomy is associated with a higher complete response (ypT0N0) rate than standard NAC. These data highlight and suggest the need to further investigate ddMVAC vs standard NAC in a prospective, randomized fashion.

Cited by 116 publications

References 40 publications

Immunohistochemistry-based taxonomical classification of bladder cancer predicts response to neoadjuvant chemotherapy

Immunohistochemistry-based taxonomical classification of bladder cancer predicts response to neoadjuvant chemotherapy

Neoadjuvant therapy in urothelial cancer

The role of complete TURBT before radical cystectomy for organ-confined bladder cancer

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