Boorjian, Stephen A.

Objective To investigate the association between smoking status and pathological response to cisplatin‐based neoadjuvant chemotherapy ( NAC ) and survival outcomes in patients with muscle‐invasive bladder cancer ( MIBC ) treated with radical cystectomy ( RC ). Patients and Methods We reviewed 201 patients treated with NAC and RC for cT 2– cT 4N0M0 BC between 01/1999 and 01/2015. Smoking status was categorised as: ‘never', ‘former', and ‘current' smoker. Pathological response to NAC was defined as: complete (ypT0N0), partial (ypTis/Ta/T1, N0), and no response (ypT2–4 or ypN+). Clinicopathological characteristics were analysed according to smoking status. Logistic regression analyses tested the association between smoking status and pathological response to NAC . Cox regression analyses tested risk factors associated with recurrence, overall ( OM ) and cancer‐specific mortality ( CSM ). Results Overall, there were 58 (28.9%) never smokers, 87 (43.3%) former smokers, and 56 (27.9%) current smokers. No response to NAC was more frequently noted in current smokers (73.2%; P = 0.007). Former smoker ( odds ratio [OR] 2.28; P = 0.024) and current smoker statuses ( OR 4.52; P < 0.001) were significantly associated with no response to NAC , after adjusting for age, gender, Charlson Comorbidity Index, and clinical stage. Similarly, current smoking status ( hazard ratio [HR] 2.14; P = 0.03) and extravesical pathological tumour stage ( HR 3.31; P < 0.001) were independently associated with an increased risk of recurrence after RC . Conclusion Cigarette smoking was significantly associated with adverse pathological response to cisplatin‐based NAC in patients with MIBC treated with RC . Current smokers were at significantly higher risk of disease recurrence as compared to former and never smokers.

Objective To investigate the prognostic significance of various patterns of extrarenal extension that comprise pathological stage T3a clear‐cell renal cell carcinoma (ccRCC) amongst patients undergoing nephrectomy for non‐metastatic disease. Patients and Methods A retrospective review of 563 patients who underwent radical nephrectomy for pathologically confirmed T3aN0/NxM0 ccRCC between 1970 and 2011 was performed. All pathological slides were re‐reviewed by one urological pathologist. Associations of patterns of extrarenal extension (perinephric fat [PF], renal sinus fat [SF], and renal vein [RV], in isolation or in any combination) with disease progression, cancer‐specific mortality (CSM), and all‐cause mortality were evaluated on multivariable analyses. Results Overall, PF invasion, renal SF invasion, and RV tumour thrombus were present in 144 (26%), 51 (9%), and 163 (29%) patients, respectively, with multiple patterns of extrarenal extension identified in 205 (36%) patients. There were no significant differences in survival outcomes for isolated involvement of PF, renal SF, or RV. However, patients with multiple patterns of extrarenal extension were at significantly increased risk of disease progression (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.04–1.65; P = 0.020), CSM (HR 1.64, 95% CI 1.27–2.12; P < 0.001), and all‐cause mortality (HR 1.32, 95% CI 1.08–1.61; P = 0.008). Conclusions The presence of multiple patterns of extrarenal extension is associated with a higher risk of disease progression and cancer‐related death after radical nephrectomy compared to isolated involvement of the PF, renal SF, or RV, which carry similar prognostic weight. If validated, these findings may help refine risk stratification of non‐metastatic T3a RCC by distinguishing patients with multiple vs one pattern of extrarenal extension.