Poor prognosis of bladder cancer patients with occult lymph node metastases treated with neoadjuvant chemotherapy

• Published in: BJU international 2018-10, Vol.122 (4), p.627-632
• Main Authors: Cha, Eugene K., Sfakianos, John P., Sukhu, Ranjit, Yee, Alyssa M., Sjoberg, Daniel D., Bochner, Bernard H.
• Format: Article
• Language: English
• Subjects: Aged; BCSM; Biopsy; Bladder cancer; BladderCancer; Chemotherapy; Clinical trials; Cystectomy; Disease-Free Survival; Female; Humans; Invasiveness; Kaplan-Meier Estimate; lymph node metastasis; Lymph nodes; Lymph Nodes - pathology; Lymphatic Metastasis - pathology; Lymphatic system; Male; Medical prognosis; Metastases; Middle Aged; neoadjuvant chemotherapy; Neoadjuvant Therapy - statistics & numerical data; Neoplasm Recurrence, Local - mortality; Neoplasm Recurrence, Local - pathology; Prognosis; radical cystectomy; Risk factors; Sensitivity analysis; Treatment Outcome; Urinary Bladder Neoplasms - mortality; Urinary Bladder Neoplasms - pathology; Urinary Bladder Neoplasms - therapy; Urothelial carcinoma
• ISSN: 1464-4096; 1464-410X
• DOI: 10.1111/bju.14242

Objectives To characterise the outcomes of neoadjuvant chemotherapy (NAC) pre‐treated patients found to be lymph node (LN)‐positive at the time of radical cystectomy and pelvic lymph node dissection (RC/PLND) for urothelial carcinoma of the bladder (UCB). Patients and Methods Of 1484 patients treated with RC/PLND for UCB from 2000 to 2010, we analysed 198 patients with clinically non‐metastatic (cN0M0) muscle‐invasive UCB who were found to be LN‐positive at RC/PLND. As patients not receiving perioperative chemotherapy were significantly older and comorbid, we compared LN‐positive patients previously treated with NAC (32 patients) to LN‐positive patients treated with adjuvant chemotherapy (AC, 49 patients) using Cox proportional hazards models. A sensitivity analysis was designed to account for the additional time to RC in NAC patients. Results The 3‐year recurrence‐free survival estimate for LN‐positive NAC patients was 26%, compared with 60% for LN‐positive AC patients. LN‐positive patients treated with NAC had significantly higher risks of disease recurrence and cancer‐specific mortality in univariate analyses (hazard ratio [HR] 2.86, 95% confidence interval [CI] 1.58–5.19, P = 0.001 and HR 2.50, 95% CI 1.34–4.65, P = 0.004, respectively) and multivariable analyses adjusting for pathological stage and LN density (HR 3.11, 95% CI 1.59–6.07, P = 0.001 and HR 3.05, 95% CI 1.46–6.35, P = 0.003, respectively). Sensitivity analyses similarly demonstrated worse outcomes for NAC pre‐treated LN‐positive patients. Conclusion LN‐positive patients previously treated with NAC have a poor prognosis, significantly worse than LN‐positive patients subsequently treated with AC, and should be considered for protocols using sandwich chemotherapy approaches or novel agents. These results should be considered in the interpretation of and stratification for clinical trials.