Clinicopathological outcomes after radical cystectomy for clinical T2 urothelial carcinoma: further evidence to support the use of neoadjuvant chemotherapy

Abstract

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Systemic chemotherapy for muscle‐invasive bladder cancer is underutilized. Currently, debate centers on whether patients should be given neoadjuvant chemotherapy or be given chemotherapy after surgery, depending on the pathology of the specimen. In this paper, we found that greater than 73% of patients had evidence of bladder cancer that was locally advanced, a criteria that would designate these patients for adjuvant chemotherapy. Using this evidence and the knowledge that neoadjuvant chemotherapy confers a survival advantage, we argue that neoadjuvant chemotherapy should be the standard of care. OBJECTIVE To evaluate the clinicopathological outcomes for patients with clinical T2 (cT2) urothelial carcinoma treated with radical cystectomy (RC) without neoadjuvant chemotherapy (NC). PATIENTS AND METHODS We identified 212 patients with cT2 tumours who underwent RC at our institution without NC. Pathological assessment of RC specimens was correlated with clinical stage. The impact of various clinicopathological factors on the outcome of patients with cT2 disease was analysed. RESULTS In total, 153/212 (73.2%) patients with cT2 bladder cancer had either pT3/T4 or pN+ tumours at RC. Moreover, only 58/153 (37.9%) of these patients received adjuvant chemotherapy. The median follow‐up was 28 (months 0.6–107.5) (range). The 5‐year recurrence‐free survival and cancer‐specific survival (CSS) was 56.5% and 59.5%, respectively. On multivariate analysis, increasing age (hazard ratio [HR] 1.04; P= 0.04), advanced pathological stage (HR 1.83; P= 0.02), and positive lymph nodes (HR 3.72; P= 0.001) were adversely associated with CSS, while receipt of adjuvant chemotherapy was protective of disease‐specific mortality (HR 0.45; P= 0.04). CONCLUSIONS Pathological upstaging is prevalent and survival remains modest in patients with cT2 tumours treated with RC without NC. Unfortunately, only 40% of patients that had locally advanced and/or regionally metastatic disease received adjuvant treatment. These data further support the value of NC for patients with muscle‐invasive bladder cancer, even in those with apparent clinically organ‐confined tumours.

Scoring system development for prediction of extravesical bladder cancer

“…We found that abnormal imaging was a strong independent predictor and control for other predictors, those patients with hydronephrosis had nearly fourfold increases in the risk of advanced MIBC. The independent prognostic value of hydronephrosis was further confirmed in another series of cT2 disease as predictor of extravesical disease 24 these factors in our scoring system resulted in the AUC of 0.79, which is statistically better than a model including only variables proposed by Karakiewicz et al 4 and similar to other reports (0.79-0.85) 1,3,6,7 .…”

Preoperative lymphocyte-to-monocyte ratio predicts clinical outcome in patients undergoing radical cystectomy for transitional cell carcinoma of the bladder: a retrospective analysis

“…The neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios have been shown to be valuable prognostic markers in patients with various types of tumors [4-9], including bladder cancer [10,11]. Risk stratification based on clinicopathologic data is insufficient to support treatment-related choices in patients with bladder cancer [12]. Novel prognostic markers that aid in stratifying patients and making treatment-related decisions are therefore necessary.…”

Neoadjuvant chemotherapy (NC) should be administered to fit patients with newly diagnosed, potentially resectable muscle-invasive urothelial cancer (MIUC) of the bladder – A 2013 CAGMO Consensus Statement and Call for a Streamlined Referral Process

“…Another reason to offer NC to patients with cT2 disease is that a significant number of patients are upstaged at the time of RC. Contemporary series show that up to 73% of patients with cT2 disease are actually upstaged at RC, 27 and as such may derive greater relative benefit from NC than initially expected preoperatively. Encouraging data from a recent Canadian survey of medical oncologists and urologists suggests that 96% and 88%, respectively would offer NC, however the referral rate and use of NC is still relatively low.…”