Cigarette smoking is associated with adverse pathological response and increased disease recurrence amongst patients with muscle‐invasive bladder cancer treated with cisplatin‐based neoadjuvant chemotherapy and radical cystectomy: a single‐centre experienc
BJU International | January 9, 2019 | Volume: 123 | Issue: 6 | Pages: 1011-1019
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.
Heterogeneity of risk within Gleason 4 + 4, 4 + 5 and 5 + 4 prostate cancer
Scandinavian Journal of Urology | January 2, 2019 | Volume: 52 | Issue: 5-6 | Pages: 340-348
Background: There are conflicting data regarding the impact of obesity on postoperative outcomes following radical cystectomy (RC) and how obesity and malnutrition interact in patients undergoing RC. Objective: To evaluate associations of body mass index (BMI), significant preoperative weight loss, and hypoalbuminemia with 30-day complications and mortality after RC. Methods: Review of the American College of Surgeons National Surgical Quality Improvement Program database identified 2,055 patients who underwent RC (2006-12). Univariate and multivariable logistic regression models were developed to assess associations between hypoalbuminemia (<3.5 g/dL), >10% preoperative weight loss, obesity as characterized by BMI (class I: 30–34.9, II: 35–39.9, III: ≥40 kg/m 2 ), and 30-day complications and mortality. Results: The median BMI of the study cohort was 27.82 kg/m 2 with 22.4% classified as having class I, 7.5% class II, and 4.2% class III obesity, respectively. Hypoalbuminemia and >10% weight loss were present in 16.7% and 3.5%, respectively. Among obese patients, 13.4% had hypoalbuminemia. On multivariable analysis, class I (OR 1.43, p = 0.01), class II (OR 1.92, p < 0.001), and class III (OR 2.32, p < 0.001) obesity and hypoalbuminemia (OR 1.47, p = 0.02) were independently associated with 30-day complications, and class III obesity (OR 2.96, p = 0.02) and hypoalbuminemia (OR 2.33, p = 0.03) were independently associated with 30-day mortality. Conclusion: Increasing class of obesity and hypoalbuminemia were independently associated with increased complications following RC. Hypoalbuminemia and class III obesity were associated with early mortality. This study highlights the fact that malnutrition may coexist in obese patients and underscores the need to identify patients with malnutrition who may be candidates for preoperative nutritional optimization.
Nutritional Predictors of Perioperative Complications and Mortality Following Nephrectomy for Renal Malignancies: A Population-Based Analysis
Kidney Cancer | August 1, 2018 | Volume: 2 | Issue: 2 | Pages: 147-174
Introduction and Objective: Conflicting data exists regarding the impact of body mass index (BMI) on postoperative outcomes following surgery for renal malignancies (RM). Herein, we investigated associations between obesity, hypoalbuminemia, and/or significant weight loss in the preoperative period, and risk complications and mortality within 30 days of radical (RN) or partial nephrectomy (PN). Materials and Methods: Review of the American College of Surgeons National Surgical Quality Improvement Program database identified 8,618 patients treated with PN or RN for RM between 2005 and 2012. Univariate and multivariable logistic regression models were developed to assess associations between hypoalbuminemia (<3.5 g/dl), >10% weight loss within 6 months of surgery, obesity (BMI >30 kg/m 2 ), and 30-day major complications and mortality. Results: Median BMI was 29.2 kg/m 2 with 24.9%, 11.9%, and 8.2% having class I, II, and III obesity, respectively. Weight loss of >10% was observed in 2.6% and 15.4% had preoperative albumin<3.5 g/dl. There were 1,802 complications (20.9%) and 88 deaths within 30 days (1.0%). On multivariable analysis, BMI ≥40 kg/m 2 (OR 1.3, p = 0.04), >10% weight loss (OR 1.9, p < 0.001) and hypoalbuminemia (OR 1.5, p < 0.001) were independently associated with 30-day complications, while only >10% weight loss was independently associated with 30-day mortality (OR 2.4, p = 0.03). Conclusions: Extreme obesity, hypoalbuminemia, and significant weight loss were independently associated with risk of significant complications following PN or RN while only significant preoperative weight loss was associated with early mortality, underscoring the need to further understand the utility of moderating these risk factors in the perioperative period.
The Association of Aspirin Use with Survival Following Radical Cystectomy
Journal of Urology | May 29, 2018 | Volume: 200 | Issue: 5 | Pages: 1014-1021
703 Background: Clinical and pathologic factors alone have limited prognostic ability in patients with metastatic clear cell renal cell carcinoma (ccRCC). We sought to determine if tissue biomarkers, along with our previously reported clinical metastases score, can be used to predict cancer specific survival (CSS) in patients with metastatic ccRCC. Methods: Patients with metastatic ccRCC who underwent nephrectomy between 1990-2004 were identified using the Mayo Clinic Nephrectomy Registry. Sections from paraffin-embedded primary tumor tissue blocks were used for immunohistochemistry staining for PD-1, B7-H1 (PD-L1), B7-H3, Bim (downstream pro-apoptotic signaling molecule in PD-1 pathway), CA-IX, IMP3, Ki67, and survivin. CSS was the primary outcome. Biomarkers that were significantly associated with CSS after adjusting for the metastases score were used to develop a biomarker-specific multivariable model using a bootstrap resampling approach and forward selection. Predictive ability was summarized using a bootstrap-corrected c-index. Results: The cohort included 602 patients, 192 (32%) with metastases at diagnosis and 410 (68%) who developed metastases after nephrectomy. Median follow-up among survivors was 9.6 years (IQR 4.2,12.8) and 504 patients died of RCC. Bim, IMP3, Ki67, and survivin expression were significantly associated with CSS after adjusting for the metastases score and were used to develop a biomarker-specific model. High Bim (HR 1.44; 95%CI 1.16-1.78; p < 0.001), high survivin (HR 1.35; 95%CI 1.08-1.68; p = 0.008), and the metastases score (HR 1.13 per one point; 95%CI 1.10-1.16; p < 0.001) were retained as independent predictors in the final multivariable model (c-index 0.69). Conclusions: We created a prognostic model combining the clinical metastases score and two primary tissue expression biomarkers, Bim and survivin, for patients with metastatic RCC who underwent nephrectomy. External validation will be required prior to clinical use.
Independent Validation of the American Joint Committee on Cancer 8th Edition Prostate Cancer Staging Classification
Journal of Urology | June 29, 2017 | Volume: 198 | Issue: 6 | Pages: 1286-1294