Shreyas Joshi

Treatment Trends and Outcomes for Patients With Lymph Node–Positive Cancer of the Penis

Importance Penile cancer is an uncommon disease with minimal level I evidence to guide therapy. The National Comprehensive Cancer Network (NCCN) guidelines advocate a lymph node dissection (LND) or radiotherapy with consideration of perioperative chemotherapy for all patients with lymph node–positive (LN+) penile cancer without metastasis. Objectives To determine temporal trends in use of chemotherapy for patients with LN+ penile cancer without metastasis and to evaluate outcomes between those who did or did not receive LND, chemotherapy, and radiotherapy. Design, Setting, and Participants The US National Cancer Database (NCDB) was queried for all 1123 patients with LN+, squamous cell carcinoma of the penis without metastasis from January 1, 2004, through December 31, 2014. Temporal trends were assessed using Cochran-Armitage tests. Multivariable logistic models were used to examine the association between treatments, clinicopathologic variables, and receipt of chemotherapy. Kaplan-Meier analyses with log-rank tests and multivariable Cox regressions were used to analyze overall survival. Data were analyzed between January 2017 and September 2017. Main Outcomes and Measures Use of chemotherapy over time. Survival outcomes by receipt or nonreceipt of LND, radiotherapy, and chemotherapy. Results Of 1123 patients identified, most were white (924 [82.3%]) vs African American (141 [12.6%]) or of other or unknown race (58 [5.2%]). The age of most patients (727 [64.7%]) was between 50 and 75 years, and 750 patients (66.8%) underwent an LND. From 2004 to 2014, the use of systemic therapy significantly increased (26 of 68 patients, 38.2% vs 65 of 136, 47.8%; P < .001). However, only 177 of 335 patients with N3 disease (52.8%) received chemotherapy (N1: 106 of 338, 31.4%; N2: 178 of 450, 39.6%). Following adjustment, older patients (>76 years: OR, 0.28; 95% CI, 0.15-0.50; P < .001) were less likely to receive chemotherapy. Patients who received radiotherapy (OR, 4.38; 95% CI, 3.10-6.18; P < .001) and those patients with N2 (OR, 1.62; 95% CI, 1.16-2.27; P = .005) or N3 (OR, 2.32; 95% CI, 1.67-3.22; P < .001) cancer were more likely to receive chemotherapy. On multivariable analysis, LND (HR, 0.64; 95% CI, 0.52-0.78; P < .001) was associated with better overall survival, while neither chemotherapy (HR, 1.01; 95% CI, 0.80-1.26; P = .95) nor radiotherapy (HR, 0.85; 95% CI, 0.70-1.04; P = .11) was associated with overall survival. Conclusions and Relevance In hospitals reporting to the NCDB, only 66.8% of patients with LN+ penile cancer received an LND. While chemotherapy use has increased since 2004, rates remain low (52.8% for patients with N3 cancer). Receipt of LND, but not chemotherapy or radiotherapy, is associated with overall survival. This may reflect the aggressive natural history of penile cancer as well as the inherent analysis limitation of a relatively small sample size. These data highlight opportunities to improve adherence to guideline-recommended care.

Renal Tumor Anatomic Complexity: Clinical Implications for Urologists

Anatomic tumor complexity can be objectively measured and reported using nephrometry. Various scoring systems have been developed in an attempt to correlate tumor complexity with intraoperative and postoperative outcomes. Nephrometry may also predict tumor biology in a noninvasive, reproducible manner. Other scoring systems can help predict surgical complexity and the likelihood of complications, independent of tumor characteristics. The accumulated data in this new field provide provocative evidence that objectifying anatomic complexity can consolidate reporting mechanisms and improve metrics of comparisons. Further prospective validation is needed to understand the full descriptive and predictive ability of the various nephrometry scores.

Understanding Mutational Drivers of Risk: An Important Step Toward Personalized Care for Patients with Renal Cell Carcinoma

The identification of clinically relevant genetic mutations in renal cell carcinoma is an important step on the path toward personalized management of this disease.

Treatment Facility Volume and Survival in Patients with Metastatic Renal Cell Carcinoma: A Registry-based Analysis

BACKGROUND Higher treatment facility (TF) volume has been linked with improved oncologic treatment outcomes. OBJECTIVE To determine the association between TF volume and overall survival in patients with metastatic renal cell carcinoma (mRCC). DESIGN, SETTING, AND PARTICIPANTS The National Cancer Database (NCDB) was queried for all patients with mRCC with survival data available (2004-2013, cohort A). Overall survival was assessed based on TF volumes, and increasingly narrow inclusion criteria were used to confirm the cohort A association: cohort B=mRCC patients with active treatment; cohort C=mRCC patients with systemic therapy; cohort D=mRCC patients with systemic therapy at the reporting institution; and cohort E=mRCC patients with systemic therapy at the reporting institution with known liver and lung metastatic status. Sensitivity analyses were also performed on subcohorts of mRCC who never underwent a nephrectomy (C1, D1, and E1). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The effect of volume on time to death (from any cause) was determined using Cox regression models, adjusting for multiple clinical pathologic factors. Volume effects (assessed continuously) were modeled using flexible cubic splines, and adjusted 1-yr survivals were obtained from the model. RESULTS AND LIMITATIONS A total of 41 836 mRCC patients were treated at 1222 TFs. The median age was 65 yr. Of the patients, 66% were men and 79% had clear cell mRCC. Median TF volume was 2.2 patients per year (pts/yr). Across all cohorts, higher TF volume was associated with improved outcomes. Adjusted 1-yr survival in cohort A was 0.36 at 2 pts/yr, 0.39 at 5 pts/yr, 0.42 at 10 pts/yr, and 0.46 at 20 pts/yr, with similar magnitudes of effect in cohorts B-E. Limitations include the retrospective nature of NCDB analysis and the lack of information on treatment regimens used at specific facilities, which may explain mechanisms of effects. CONCLUSIONS Higher facility volume is associated with improvements in survival for patients being treated for mRCC. Steps should be taken to standardize management of mRCC patients, such as evidence-based pathway development, clinical trial access, and multidisciplinary resource availability at lower-volume TFs. PATIENT SUMMARY In this report, we analyzed a large cancer database and found that patients with metastatic kidney cancer survived longer if they were managed at facilities that treated a higher volume of such patients. This information can help find the best treatment environment for patients with metastatic kidney cancer.

Differences in Survival Associated with Performance of Lymph Node Dissection in Patients with Invasive Penile Cancer: Results from the National Cancer Database

Purpose: Inguinal lymphadenectomy remains under performed in patients with invasive penile cancer. Using a large national cancer registry we assessed temporal trends in inguinal lymphadenectomy performance and evaluated the impact of the procedure on survival in patients in whom inguinal lymphadenectomy was an absolute indication (T1b‐4 N0/x‐1) according to NCCN® (National Comprehensive Cancer Network®) Guidelines®. Materials and Methods: We queried the National Cancer Database for all cases of nonmetastatic, T1b‐4 N0/x‐1 squamous cell carcinoma of the penis from 2004 to 2014. Multivariable logistic regression models adjusting for patient, demographic, and clinicopathological characteristics were used to examine the association between available covariates and receipt of inguinal lymphadenectomy. Cox proportional hazards regression analysis was then done to assess the impact of clinical and pathological variables on overall survival. Propensity score weighted analysis was performed to assess the effect of inguinal lymphadenectomy on overall survival. Results: A total of 2,224 patients met analysis criteria, of whom 606 (27.2%) underwent inguinal lymphadenectomy. Following adjustment the procedure was more likely in younger patients, those who presented with palpable adenopathy (cN1), those treated at an academic facility and those with a more contemporary diagnosis. On survival analysis controlling for all known and measured confounders inguinal lymphadenectomy was associated with improved overall survival (HR 0.79, 95% CI 0.74–0.84, p <0.001). Conclusions: At hospitals that report to the National Cancer Database the overall rate of inguinal lymphadenectomy in patients with invasive penile cancer was only 27.2%. Inguinal lymphadenectomy was associated with increased overall survival, justifying the procedure as an important quality metric for performance reporting in patients with invasive penile cancer.

Renal Hilar Lesions: Biological Implications for Complex Partial Nephrectomy

OBJECTIVE To perform a comprehensive histopathologic review of sporadic resected solitary cT1 renal masses comparing those with and without radiographic involvement of the hilum. MATERIALS AND METHODS A prospectively maintained database was queried for all cT1 renal masses undergoing resection classified per the R.E.N.A.L. nephrometry score. Hilar masses were defined as tumors that abut the main renal artery or vein on cross-sectional imaging. Demographic, treatment, renal mass, and histopathologic characteristics were compared between hilar and nonhilar renal masses. Multivariate regression model analyses were performed to assess factors associated with renal mass upstaging and disease recurrence. RESULTS A total of 1324 stage 1 renal masses met criteria for analysis of which 226 (17.1%) were defined as hilar. Hilar masses were larger, scored with higher complexity, and more likely to undergo a radical nephrectomy. On histopathologic analysis, we found no difference between hilar and nonhilar masses regarding the incidence of malignancy, presence of high nuclear grade, or risk of upstaging. On multivariate analysis, a tumors hilar location was not associated with upstaging or disease recurrence. CONCLUSION We present a comprehensive histopathologic review of a large cohort of cT1 hilar lesions noting no difference in the risk of malignancy, high nuclear grade, upstaging, or recurrence when compared to nonhilar lesions. Together, these data suggest that there is no compelling cancer-specific rationale to perform a radical nephrectomy when managing renal hilar tumors.

What can the National Cancer Database tell us about disparities in advanced bladder cancer outcomes

Advanced bladder cancer is largely a lethal disease that has demonstrated little improvement in survival trends over the past 50 years. Five-year survival for advanced bladder cancer has remained at about 8% since 1973; though, as in most diseases, survival outcomes are not evenly distributed among different sociodemographic groups (1).

Resistance to Systemic Therapies in Clear Cell Renal Cell Carcinoma: Mechanisms and Management Strategies

Renal cell carcinoma (RCC) is the most common form of kidney cancer. It is categorized into various subtypes, with clear cell RCC (ccRCC) representing about 85% of all RCC tumors. The lack of sensitivity to chemotherapy and radiation therapy prompted research efforts into novel treatment options. The development of targeted therapeutics, including multi-targeted tyrosine kinase inhibitors (TKI) and mTOR inhibitors, has been a major breakthrough in ccRCC therapy. More recently, other therapeutic strategies, including immune checkpoint inhibitors, have emerged as effective treatment options against advanced ccRCC. Furthermore, recent advances in disease biology, tumor microenvironment, and mechanisms of resistance formed the basis for attempts to combine targeted therapies with newer generation immunotherapies to take advantage of possible synergy. This review focuses on the current status of basic, translational, and clinical studies on mechanisms of resistance to systemic therapies in ccRCC. Mol Cancer Ther; 17(7); 1355–64. ©2018 AACR.

PD62-06 NEOADJUVANT CHEMOTHERAPY FOR ELDERLY PATIENTS WITH LOCALLY ADVANCED OR EARLY NODAL DISEASE: ARE WE DOING ENOUGH?

evaluated (RECIST criteria): CR was observed in 2 pts (6%), PR in 18 (60%); PD in 1 (3%) and SD in 9 (30%) regarding primary bladder tumor. In 12 pts with enlarged lymph-nodes, the response to NGC was CR in 1, PR in 10 and SD in 1. Patients receiving neoadjuvant GC had a greater chance of achieving a pathologically lower stage compared to the untreated population: organ-confined cancer in 53,3% (16/30) vs. 33% (p < 0.001). Lymph-node metastasis resulted in 25% patients after GC (n1⁄410) vs 45.5% of untreated patients (n1⁄420; p < 0.001). Considering patients resulted CR and PR after NGC (n1⁄420), 70% had down-staging on pathologic report after RC. Complication rates were higher in NGC group (4 thromboembolisms; 2 sepsis; 12 hematologic complications); all complications were not related to surgery. Pathological TRG after NGC was not correlated to clinical regression grade. The OS (mean follow-up 30 months) of patients who received NGC resulted of 66.6% compared with 56% of patients undergoing cystectomy alone (p<0,001). Fifty percent of patients in NGC group were alive without cancer vs 40,1% in cystectomy alone group (p<0,001). CONCLUSIONS: Neoadjuvant chemotherapy for muscle-invasive bladder cancer increases the rate of down-staging and cancer specific survival. NGC is associated with an increased risk of complications that may be prevented using tailored strategies. Pathological regression grades after NGC are not correlated to RECIST criteria based on CT.

MP59-12 VALIDATION OF A MATHEMATICAL MODEL TO PREDICT RENAL FUNCTION AFTER NEPHRON SPARING SURGERY

before and after partial nephrectomy, and compare the findings with 99mTc-DMSA renal scan. METHODS: The data of 51 patients with a unilateral renal tumor managed by partial nephrectomy were retrospectively analyzed. The RCV of tumor-bearing and contralateral kidneys was measured using ImageJ software. Split estimated glomerular filtration rate (eGFR) and SRV calculated using this RCV were compared with the split renal function (SRF) measured with 99mTc-DMSA renal scan. RESULTS: A strong correlation between SRF and SRV of the tumor-bearing kidney was observed before and after surgery (r 1⁄4 0.89, p < 0.001 and r 1⁄4 0.94, p < 0.001). The preoperative and postoperative split eGRF of the operated kidney showed moderate correlation with SRF (r 1⁄4 0.39, p 1⁄4 0.004 and r 1⁄4 0.49, p < 0.001). Correlation between reductions in SRF and SRV of the operated kidney (r 1⁄4 0.87, p < 0.001) was stronger than that between SRF and percent reduction in split eGFR (r 1⁄4 0.64, p < 0.001). CONCLUSIONS: Compared with split eGFR, the SRV calculated using CT-based renal volumetry has a strong correlation with the SRF measured using 99mTc-DMSA renal scan. CT-based SRV measurement before and after partial nephrectomy can be used as a single modality for anatomical and functional assessment of the tumor-bearing kidney.