Max Kates

Survival following lobectomy and limited resection for the treatment of stage I non-small cell lung cancer<=1 cm in size: a review of SEER data.

BACKGROUND Although lobectomy is the standard treatment for stage I non-small cell lung cancer (NSCLC), recent studies have suggested that limited resection may be a viable alternative for small-sized tumors. The objective of this study was to compare survival after lobectomy and limited resection among patients with stage IA tumors≤1 cm by using a large, US-based cancer registry. METHODS Using the Surveillance, Epidemiology, and End Results (SEER) registry, we identified 2,090 patients with stage I NSCLC≤1 cm in size who underwent lobectomy or limited resection (segmentectomy or wedge resection). We used propensity score analysis to adjust for potential differences in the baseline characteristics of patients in the two treatment groups. Overall and lung cancer-specific survival rates of patients undergoing lobectomy vs limited resection were compared in stratified and adjusted analyses, controlling for propensity scores. RESULTS Overall, 688 (33%) patients underwent limited resection. For the entire cohort, we were not able to identify a difference in outcomes among patients treated with lobectomy vs limited resection, as demonstrated by an adjusted hazard ratio (HR) for overall survival (1.12; 95% CI, 0.93-1.35) and lung cancer-specific survival (HR, 1.24; 95% CI, 0.95-1.61). Similarly, when the cohort was divided into propensity score quintiles, we did not find a difference in survival rate between the two groups. CONCLUSIONS Limited resection and lobectomy may lead to equivalent survival rates among patients with stage I NSCLC tumors≤1 cm in size. If confirmed in prospective studies, limited resection may be preferable for the treatment of small tumors because it may be associated with fewer complications and better postoperative lung function.

Survival after partial and radical nephrectomy for the treatment of stage T1bN0M0 renal cell carcinoma (RCC) in the USA: a propensity scoring approach

Study Type – Therapy (cohort)

Post-Percutaneous Nephrolithotomy Systemic Inflammatory Response: A Prospective Analysis of Preoperative Urine, Renal Pelvic Urine and Stone Cultures

PURPOSE Prior studies suggest that renal pelvic urine culture is a more accurate predictor of urosepsis. We prospectively determined the correlation between preoperative bladder urine cultures, intraoperative renal pelvis cultures and stone cultures in patients undergoing percutaneous nephrolithotomy. We also examined post-procedure risk factors for systemic inflammatory response syndrome. MATERIALS AND METHODS From February 2009 to February 2011 urine samples from the bladder and renal pelvis were collected from patients undergoing percutaneous nephrolithotomy. Extracted stones were also sent for culture analysis. Postoperatively patients were closely monitored for any signs of systemic inflammatory response syndrome. The concordance of urine and stone cultures across different sites was examined. Regression analysis was done to identify clinical variables associated with systemic inflammatory response syndrome. RESULTS A total of 204 percutaneous nephrolithotomies were done in 198 patients, of whom 20 (9.8%) had evidence of systemic inflammatory response syndrome postoperatively, including 6 (30%) requiring intensive care. The concordance among stone, renal pelvic and preoperative cultures was 64% to 75% with the highest concordance between renal pelvic urine and stone cultures. In a multivariate model multiple access tracts and a stone burden of 10 cm(2) or greater were significant predictors of systemic inflammatory response syndrome postoperatively. CONCLUSIONS Even appropriately treated preoperative urinary infections may not prevent infected urine at percutaneous nephrolithotomy. Renal pelvic urine and stone cultures may be the only way to identify the causative organism and direct antimicrobial therapy. We recommend collecting pelvic urine and stone cultures to identify the offending organism in patients at risk for sepsis, particularly those with a large stone burden requiring multiple access tracts.

Increased Risk of Overall and Cardiovascular Mortality After Radical Nephrectomy for Renal Cell Carcinoma 2 cm or Less

PURPOSE We used a large, population based registry to assess whether a difference in overall and cardiovascular survival may exist between radical nephrectomy and partial nephrectomy for renal cell carcinoma 2 cm or less. MATERIALS AND METHODS From the SEER (Surveillance, Epidemiology and End Results) registry we identified 4,216 patients with histologically confirmed renal cell carcinoma 2 cm or less who were treated with partial or radical nephrectomy. Patient and tumor characteristics were compared between the 2 patient groups. Multivariate logistic regression was done to predict the odds of undergoing radical nephrectomy. Cardiovascular survival and overall survival were compared between the 2 cohorts, adjusting for patient and tumor characteristics. RESULTS Overall 2,301 patients (55%) underwent partial nephrectomy. Partial nephrectomy use steadily increased during the study period from 27% of all cases in 1998 to 66% in 2007. Patients who underwent partial nephrectomy were an average of 2.5 years younger than those treated with radical nephrectomy (56.4 vs 58.9 years, p <0.001). They were more likely to be white and from the western or northeastern United States. Older age was the only independent predictor of radical nephrectomy (OR 1.02, 95% CI 1.01-1.03). When controlling for patient characteristics and surgery year, radical nephrectomy was associated with worse overall mortality (HR 2.24, 95% CI 1.75-2.84) and cardiovascular mortality (HR 2.53, 95% CI 1.51-4.23). CONCLUSIONS Radical nephrectomy is associated with worse overall and cardiovascular survival compared to partial nephrectomy in patients with localized renal cell carcinoma 2 cm or less. These findings justify the widespread application of nephron sparing techniques to treat localized kidney cancer.

Validation of a frailty index in patients undergoing curative surgery for urologic malignancy and comparison with other risk stratification tools.

OBJECTIVE To retrospectively validate and compare a modified frailty index predicting adverse outcomes and other risk stratification tools among patients undergoing urologic oncological surgeries. MATERIALS AND METHODS The American College of Surgeons National Surgical Quality Improvement Program was queried from 2005 to 2013 to identify patients undergoing cystectomy, prostatectomy, nephrectomy, and nephroureterectomy. Using the Canadian Study of Health and Aging Frailty Index, 11 variables were matched to the database; 4 were also added because of their relevance in oncology patients. The incidence of mortality, Clavien-Dindo IV complications, and adverse events were assessed with patients grouped according to their modified frailty index score. RESULTS We identified 41,681 patients who were undergoing surgery for presumed urologic malignancy. Patients with a high frailty index score of >0.20 had a 3.70 odds of a Clavien-Dindo IV event (CI: 2.865-4.788, P<0.0005) and a 5.95 odds of 30-day mortality (CI: 3.72-9.51, P<0.0005) in comparison with nonfrail patients after adjusting for race, sex, age, smoking history, and procedure. Using C-statistics to compare the sensitivity and specificity of the predictive ability of different models per risk stratification tool and the Akaike information criteria to assess for the fit of the models with the data, the modified frailty index was comparable or superior to the Charlson comorbidity index but inferior to the American Society of Anesthesiologists Risk Class in predicting 30-day mortality or Clavien-Dindo IV events. When the modified frailty index was augmented with the American Society of Anesthesiologists Risk Class, the new index was superior in all aspects in comparison to other risk stratification tools. CONCLUSION Existing risk stratification tools may be improved by incorporating variables in our 15-point modified frailty index as well as other factors such as walking speed, exhaustion, and sarcopenia to fully assess frailty. This is relevant in diseases such as kidney and prostate cancer, where surveillance and other nonsurgical interventions exist as alternatives to a potentially complicated surgery. In these scenarios, our modified frailty index augmented by the American Society of Anesthesiologists Risk Class may help inform which patients have increased surgical complications that may outweigh the benefit of surgery although this index needs prospective validation.

Validation of a Model to Predict Perioperative Mortality from Lung Cancer Resection in the Elderly

RATIONALE Surgical resection is the mainstay therapy for localized non-small cell lung cancer (NSCLC), yet elderly patients are less likely to be treated due to concerns about morbidity and mortality related to surgery. OBJECTIVES To validate and refine a clinical model to predict 30-day perioperative mortality (POM) in elderly patients undergoing curative resection for lung cancer. METHODS We identified 14,297 patients aged 65 years and older with stage I, II, or IIIA NCSLC from the Surveillance, Epidemiology, and End-Results Registry linked to Medicare claims. We used logistic regression analysis to identify independent risk factors for POM and to validate and refine a previously derived prediction model. MEASUREMENTS AND MAIN RESULTS Overall, POM was 4.6% (95% confidence interval, 4.2-4.9%). Multiple regression analysis revealed that greater age, male sex, resections of multiple lobes, advanced stage, greater tumor size, and certain comorbidities were associated with increased risk for POM. These risk factors were similar to those observed in the prior model. When patients were stratified according to their predicted risk of POM, the observed mortality increased from 1.2 to more than 10%. CONCLUSIONS Among elderly patients with lung cancer, a prediction rule can identify those patients at higher risk for fatal complications from surgery. Further studies should evaluate whether use of the model can lead to improvements in treatment decision making.

Frailty as a marker of adverse outcomes in patients with bladder cancer undergoing radical cystectomy

OBJECTIVE To investigate the modified frailty index (mFI) as a preoperative predictor of postoperative complications following radical cystectomy (RC) in patients with bladder cancer. MATERIALS AND METHODS Patients undergoing RC were identified from the National Surgical Quality Improvement Program participant use files (2011-2013). The mFI was defined in prior studies with 11 variables based on mapping the Canadian Study of Health and Aging Frailty Index to the National Surgical Quality Improvement Program comorbidities and activities of daily livings. The mFI groups were determined by the number of risk factors per patient (0, 1, 2, and≥3). Univariable and multivariable regression were performed to determine predictors of Clavien 4 and 5 complications, and a sensitivity analysis was performed to determine the mFI value that would be a significant predictor of Clavien 4 and 5 complications. RESULTS Of the 2,679 cystectomy patients identified, 843 (31%) of patients had an mFI of 0, 1176 (44%) had an mFI of 1, 555 (21%) had an mFI of 2, and 105 (4%) had an mFI≥3. Overall, 1585 (59%) of patients experienced a Clavien complication. When stratified at a cutoff of mFI≥2, the overall complication rate was not different (61.7% vs. 58.3%, P = 0.1), but the mFI2 or greater group had a significantly higher rate of Clavien grade 4 or 5 complications (14.6% vs. 8.3%, P<0.001) and overall mortality rate (3.5% vs. 1.8%, P = 0.01) in the 30-day postoperative period. The multivariate logistic regression model showed independent predictors of Clavien grade 4 or 5 complications were age>80 years (odds ratio [OR] = 1.58 [1.11-2.27]), mFI2 (OR = 1.84 [1.28-2.64]), and mFI3 (OR = 2.58 [1.47-4.55]). CONCLUSIONS Among patients undergoing RC, the mFI can identify those patients at greatest risk for severe complications and mortality. Given that bladder cancer is increasing in prevalence particularly among the elderly, preoperative risk stratification is crucial to inform decision-making about surgical candidacy.

The ratio of CD8 to Treg tumor-infiltrating lymphocytes is associated with response to cisplatin-based neoadjuvant chemotherapy in patients with muscle invasive urothelial carcinoma of the bladder

ABSTRACT Introduction: Randomized controlled trials of platinum-based neoadjuvant chemotherapy (NAC) for bladder cancer have shown that patients who achieve a pathologic response to NAC exhibit 5 y survival rates of approximately 80–90% while NAC resistant (NR) cases exhibit 5 y survival rates of approximately 30–40%. These findings highlight the need to predict who will benefit from conventional NAC and the need for plausible alternatives. Methods: The pre-treatment biopsy tissues from a cohort of 41 patients with muscle invasive bladder who were treated with NAC were incorporated in tissue microarray and immunohistochemistry for PD-L1, CD8, and FOXP3 was performed. Percentage of PD-L1 positive tumor cells was measured. Tumor-infiltrating lymphocytes (TIL) densities, along with CD8 and Treg-specific TILs, were measured. Results: TIL density was strongly correlated with tumor PD-L1 expression, consistent with the mechanism of adaptive immune resistance in bladder cancer. Tumor cell PD-L1 expression was not a significant predictor of response. Neither was the CD8 nor Treg TIL density associated with response. Intriguingly though, the ratio of CD8 to Treg TIL densities was strongly associated with response (p = 0.0003), supporting the hypothesis that the immune system plays a role in the response of bladder cancer to chemotherapy. Discussion: To our knowledge, this is the first report in bladder cancer showing that the CD8 to Treg TIL density in the pre-treatment tissues is predictive for conventional NAC response. These findings warrant further investigations to both better characterize this association in larger cohorts and begin to elucidate the underlying mechanism(s) of this phenomenon.

Immediate radical cystectomy vs conservative management for high grade cT1 bladder cancer: is there a survival difference?

Study Type – Aetiology (individual cohort)

Indications for intervention during active surveillance of prostate cancer: a comparison of the Johns Hopkins and Prostate Cancer Research International Active Surveillance (PRIAS) protocols

To analyse how patients enrolled in our biopsy based surveillance programme would fare under the Prostate Cancer Research International Active Surveillance (PRIAS) protocol, which uses PSA kinetics.