Abstract
Purpose To investigate the role of clinical parameters and immunohistochemical (IHC) biomarkers in their feasibility to predict the effect of neo-adjuvant chemotherapy (NAC) in patients with muscle-invasive urothelial bladder cancer (MIBC). Materials and methods The first 76 consecutive patients with MIBC treated with NAC and radical cystectomy in two University hospitals in Finland between 2008 and 2013 were chosen for this study. After excluding patients with non-urothelial cancer, less than two cycles of chemotherapy, no tissue material for IHC analysis or non-muscle-invasive bladder cancer in re-review, 59 patients were included in the final analysis. A tissue microarray block was constructed from the transurethral resection samples and IHC stainings of Ki-67, p53, Her-2 and EGFR were made. The correlations between histological features in transurethral resection samples and immune-histochemical stainings were calculated. The associations of clinicopathological parameters and IHC stainings with NAC response were evaluated. Factors affecting survival were estimated. Results The complete response rate after NAC was 44%. A higher number of chemotherapy cycles was associated with better response to neo-adjuvant chemotherapy. No response to neo-adjuvant chemotherapy and female gender was associated with decreased cancer-specific survival. The IHC stainings used failed to show an association with neo-adjuvant chemotherapy response and overall or cancer specific survival. Conclusions Patients who do not respond to neo-adjuvant chemotherapy do significantly worse than responders. This study could not find clinical tools to distinguish responders from non-responders. Further studies preferably with larger cohorts addressing this issue are warranted to improve the selection of patients for neo-adjuvant chemotherapy.
Highlights
Muscle invasive bladder cancer (MIBC) is a disease with poor prognosis
Almost three out of four (73%) of the patients had a high grade (WHO grade 3) urothelial carcinoma in the initial diagnosis made with Transurethral resection of bladder tumor (TURBT), but only 27% had lympho-vascular invasion (LVI)
We demonstrate here that neo-adjuvant chemotherapy (NAC) induced down-staging of non-MIBC or a complete response is associated with improved cancer-specific survival (CSS)
Summary
Muscle invasive bladder cancer (MIBC) is a disease with poor prognosis. Among patients with MIBC treated with radical cystectomy (RC) and pelvic lymphadenectomy alone, the 5year overall survival (OS) is between 25 and 77%, decreasing with more advanced stage [1,2]. Platinum-based combination neo-adjuvant chemotherapy (NAC) prior to RC improves the absolute survival of patients at 5 years by 5–7% as compared to those receiving cystectomy alone [3,4]. The rationale to use NAC is to eradicate micro-metastasis and to downstage the primary tumor. Down-staging to non-muscle invasive disease and especially complete pathological response (pT0) is associated with improved overall survival (OS) [5]. In the case of chemo-resistant tumors, NAC predisposes patients to possible adverse effects and increases the risk of cancer progression prior to surgery
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