Differences in mutations across tumour sizes in clear-cell renal cell carcinoma.

OBJECTIVE: To assess the distribution of key mutations across tumour sizes in clear-cell renal cell carcinoma (ccRCC), and secondarily to examine the prognostic impact of aggressive mutations in smaller ccRCCs. PATIENT AND METHODS: The distribution of mutations (VHL, PBRM1, SETD2, BAP1 and CDKN2A loss) across tumour sizes was assessed in 1039 ccRCCs treated with nephrectomy in cohorts obtained from the Tracking Cancer Evolution (TRACERx), The Cancer Genome Atlas (TCGA) and the Cancer Genomics of the Kidney (CAGEKID) projects. Logistic regression was used to model the presence of each mutation against size. In our secondary analysis, we assessed a subset of ccRCCs ≤7 cm for associations of key aggressive mutations (SETD2, BAP1, and CDKN2A loss) with metastasis, invasive disease and overall survival, while controlling for size. A subset of localised tumours ≤7 cm was also used to assess associations with recurrence after nephrectomy. RESULTS: On logistic regression, each 1-cm increase in tumour size was associated with aggressive mutations, SETD2, BAP1, and CDKN2A loss, at odds ratios (ORs) of 1.09, 1.10 and 1.19 (P < 0.001), whereas no significant association was observed between tumour size and PBRM1 (OR 1.02; P = 0.23). VHL was mildly negatively associated with a 1-cm increase in size (OR 0.95; P = 0.01). Among tumours ≤7 cm, SETD2 and CDKN2A loss were associated with metastatic disease at ORs of 3.86 and 3.84 (P < 0.05) while controlling for tumour size. CDKN2A loss was associated with worse overall survival, with a hazard ratio (HR) of 2.19 (P = 0.03). Among localised tumours ≤7 cm, SETD2 was associated with worse recurrence-free survival (HR 2.00; P = 0.03). CONCLUSION: Large and small ccRCCs are genomically different. Aggressive mutations, namely, SETD2, BAP1, and CDKN2A loss, are rarely observed in small ccRCCs and are observed more frequently in larger tumours. However, when present in tumours ≤7 cm, SETD2 mutations and CDKN2A loss were still independently associated with invasive disease, metastasis, worse survival, and recurrence after resection, after controlling for size.

The Role of Tumor Epithelial-Mesenchymal Transition and Macrophage Crosstalk in Cancer Progression.

PURPOSE OF REVIEW: The purpose of this review is to summarize the recently published findings regarding the role of epithelial to mesenchymal transition (EMT) in tumor progression, macrophages in the tumor microenvironment, and crosstalk that exists between tumor cells and macrophages. RECENT FINDINGS: EMT is a crucial process in tumor progression. In association with EMT changes, macrophage infiltration of tumors occurs frequently. A large body of evidence demonstrates that various mechanisms of crosstalk exist between macrophages and tumor cells that have undergone EMT resulting in a vicious cycle that promotes tumor invasion and metastasis. Tumor-associated macrophages and tumor cells undergoing EMT provide reciprocal crosstalk which leads to tumor progression. These interactions provide potential targets to exploit for therapy.

The Role of Epigenetic Change in Therapy-Induced Neuroendocrine Prostate Cancer Lineage Plasticity.

The androgen receptor (AR) signaling pathway is critical for growth and differentiation of prostate cancer cells. For that reason, androgen deprivation therapy with medical or surgical castration is the principal treatment for metastatic prostate cancer. More recently, new potent AR signaling inhibitors (ARSIs) have been developed. These drugs improve survival for men with metastatic castration-resistant prostate cancer (CRPC), the lethal form of the disease. However, ARSI resistance is nearly universal. One recently appreciated resistance mechanism is lineage plasticity or switch from an AR-driven, luminal differentiation program to an alternate differentiation program. Importantly, lineage plasticity appears to be increasing in incidence in the era of new ARSIs, strongly implicating AR suppression in this process. Lineage plasticity and shift from AR-driven tumors occur on a continuum, ranging from AR-expressing tumors with low AR activity to AR-null tumors that have activation of alternate differentiation programs versus the canonical luminal program found in AR-driven tumors. In many cases, AR loss coincides with the activation of a neuronal program, most commonly exemplified as therapy-induced neuroendocrine prostate cancer (t-NEPC). While genetic events clearly contribute to prostate cancer lineage plasticity, it is also clear that epigenetic events-including chromatin modifications and DNA methylation-play a major role. Many epigenetic factors are now targetable with drugs, establishing the importance of clarifying critical epigenetic factors that promote lineage plasticity. Furthermore, epigenetic marks are readily measurable, demonstrating the importance of clarifying which measurements will help to identify tumors that have undergone or are at risk of undergoing lineage plasticity. In this review, we discuss the role of AR pathway loss and activation of a neuronal differentiation program as key contributors to t-NEPC lineage plasticity. We also discuss new epigenetic therapeutic strategies to reverse lineage plasticity, including those that have recently entered clinical trials.

The Distribution of Metastatic Renal Cell Carcinoma by Presenting Tumor Stage in the Modern Era.

INTRODUCTION: There is a stage migration for detection of kidney cancer, thus we aim to evaluate the distribution of metastatic renal cell carcinoma by presenting clinical T stage over time. MATERIALS AND METHODS: The National Cancer Database was evaluated for patients with metastatic kidney cancer from 2010 to 2016. The primary outcome was the temporal trend of presenting clinical T stage over time. The secondary outcome was overall survival. Kaplan-Meier and Cox regression analyses were performed. RESULTS: The incidence of metastatic kidney cancer has increased, from 3426 new cases in 2010 to 4510 in 2016. While diagnosis of metastasis has increased for all tumor stages over time, there has been a more rapid increase in metastasis of localized renal masses (cT1-T2) as compared to locally advanced disease (cT3-T4). In 2010, 46% of the new metastatic cases diagnosed were cT3-T4, while in 2016 this proportion decreased to 38.2%. Conversely, metastatic cases with cT1-T2 tumors increased from 54% in 2010 to 61.9% in 2016. Cox regression noted an increased risk of death correlating with higher clinical T stage. On Kaplan Meier analysis, the 2-year survival was 29.3%, 30.3%, 28.3%, and 16.0% for cT1, cT2, cT3, and cT4, respectively (logrank P < .001). CONCLUSION: Metastatic kidney cancer is increasingly diagnosed at a lower presenting cT stage. Survival outcomes worsen with increasing cT stage in the setting of metastasis.

Clinical characteristics of renal cell carcinoma in patients under the age of 40.

BACKGROUND: Renal cell carcinoma (RCC) most commonly afflicts older patients while those 40 years old or younger represent an uncommon population. We aim to describe the tumor characteristics and treatment patterns for young kidney cancer patients utilizing the National Cancer Database. METHODS: The National Cancer Database Participant User File for RCC was queried from 2004 to 2016. Demographics and treatment trends were analyzed and compared between a young cohort, those aged 40 and younger vs. a conventional cohort, those older than 40. Pathology analyzed included clear cell, papillary, chromophobe, RCC not otherwise specified, and miscellaneous uncategorized. Subanalysis was performed for patients with localized disease and treatment type. RESULTS: Amongst the 514,879 patients diagnosed with RCC, 4.7% were ≤40 years old. RCC for individuals ≤40 has a higher proportion of female gender, non-Caucasian race, and chromophobe pathology, relative to the conventional cohort. Younger patients more often presented with cT1 disease with decreased rates of metastasis. Risk of 30-day readmission after surgery was similar between cohorts. For patients with cT1-2N0M0 disease, there was a decreasing rate of radical nephrectomy and increasing rate of partial nephrectomy; however, the conventional cohort had an increasing rate of percutaneous ablation while this remained stable in the younger cohort. CONCLUSION: Young RCC patients had a higher proportion of female gender, chromophobe histology, and favorable tumor characteristics. Partial nephrectomy has seen a dramatic increase in application regardless of age while percutaneous ablation increased only in the conventional cohort.

Unplanned Open Conversion During Radical or Partial Nephrectomy: Comparing Outcomes and Trends.

OBJECTIVES: To compare perioperative outcomes between open conversion and planned open surgical approach and to investigate trends. MATERIALS AND METHODS: The National Cancer Database (NCDB) was queried for cT1 and cT2 RCC treated by radical (RN) or partial (PN) nephrectomy between 2010 and 2016. We retrospectively analyzed patient demographics, clinical tumor characteristics, and perioperative outcomes between unplanned open conversion and planned open approaches for RN and PN. RESULTS: In total, 152,919 patients underwent RN or PN for cT1 or cT2 RCC over the 7-year span. The rate of unplanned open conversion from MIS was 3.9% overall, remaining lowest for cT1 PN (2.7%) and highest for cT2 RN (5.9%). Cases of open conversion tended to have higher rate of upstaged disease. When comparing open conversion to a planned open case, there was no difference in the length of post-operative hospitalization. On logistic regression, unplanned open conversion from MIS was associated with higher odds of positive margin for RN but not for PN. Increased odds of 30-day's readmission were associated with unplanned open conversion from MIS in the setting of cT1 PN only. CONCLUSION: When compared to a planned open approach, conversion to open from MIS does not affect length of hospital stay but is associated with higher odds of positive surgical margins for RN and higher odds of 30-day's readmission for cT1 PN. Advanced pathologic stage is associated with an open conversion, likely relating to increased tumor complexity. These findings should be considered preoperatively when determining the best surgical approach.

Stage Migration for Upper Tract Urothelial Cell Carcinoma.

INTRODUCTION: Upper tract urothelial carcinomas (UTUCs) account for 5% to 10% of urothelial cancers. The phenomenon of stage migration in tumors has been evident with increased use and higher resolution of cross-sectional imaging. Using the National Cancer Database, we analyzed trends in stage at presentation and overall survival for UTUCs. PATIENTS AND METHODS: We analyzed UTUCs in the renal pelvis or ureter from 2004 to 2016. Pathologic tumor stage data were available for 71.3% of patients and clinical tumor staging were available for 28.7% of patients. Five-year overall survival was analyzed comparing patients between 2004-2007 and 2008-2011. Tumor stage was categorized as early (0-1), intermediate (2-3), or late (4) for survival analyses. Linear regression and Kaplan-Meier analyses were utilized. RESULTS: A total of 37,210 renal pelvic and 23,200 ureteral origin UTUC cases were evaluated. Stage migration toward stage 0 and stage 4 was observed. There was a significant increase in proportion of stage 0 Ta/Tis (22.8%-33.4%, R2 = 0.86, P < .001) and stage 4 (22.3%-26.4%, R2 = 0.57, P = .003) disease for renal pelvic tumors, and a significant decrease in stages 1, 2, and 3. For UTUCs of ureteral origin, diagnosis at stage 0 Ta/Tis (37.6%-44.7%, R2 = 0.53, P = .005) and stage 4 (10.9%-14.6%, R2 = 0.63, P = .001) increased significantly, with significant reductions in stage 1 and 2. There was no difference in 5-year overall survival for ureteral or renal pelvic UTUCs for patients during 2004-2007 versus 2008-2011 when stratified by early, intermediate, or late stage. CONCLUSION: There is a stage migration toward stage 0 and stage 4 disease for UTUC. Five-year survival data from 2004 to 2011 remained stable across early, intermediate, and late stage groups.

Trends in utilization of neoadjuvant and adjuvant chemotherapy for muscle invasive bladder cancer.

PURPOSE: Previous studies have noted increased utilization of perioperative chemotherapy over time. The goal of this study was to determine trends in perioperative chemotherapy use within a contemporary population. MATERIALS AND METHODS: The National Cancer Database was queried for patients diagnosed with cT2-4N0M0 urothelial muscle invasive bladder cancer from 2011 to 2015 and underwent subsequent radical cystectomy. We retrospectively analyzed factors associated with perioperative chemotherapy and evaluated overall treatment trends in the use of neoadjuvant and adjuvant chemotherapy. Linear regression, logistic regression, Cox regression, and Kaplan-Meier analysis were performed. RESULTS: In total, 7,101 patients met inclusion criteria for analysis. The use of perioperative chemotherapy increased from 46.4% in 2011 to 57.2% in 2015 (p=0.003). Neoadjuvant chemotherapy use increased from 22.9% to 32.3% (p=0.007) over the time period analyzed, while adjuvant chemotherapy use experienced no significant change (23.5% to 24.9%, p=0.182). Logistic regression demonstrated that increased age and Charlson Comorbidity Index were predictors of not receiving chemotherapy (p<0.05), while those with increasing T stage, income above $48,000, and insurance other than Medicaid or Medicare were more likely to receive perioperative chemotherapy (p<0.05). Kaplan-Meier analysis revealed patients receiving neoadjuvant chemotherapy had the best 5-year overall survival at 48.3% compared to adjuvant chemotherapy (42.6%) or no chemotherapy (37.8%) (p<0.001). CONCLUSIONS: The increasing use of perioperative chemotherapy noted in prior studies has continued through 2015. Neoadjuvant chemotherapy appears to drive this increase while adjuvant chemotherapy utilization remains unchanged. Clinical and socioeconomic factors affect utilization of perioperative chemotherapy.

Trends in treatment of cT1 penile cancer: Analysis of the National Cancer Database.

OBJECTIVE: To characterize the treatment trends and outcomes in clinical stage T1 penile cancer using the National Cancer Database (NCDB). METHODS: The National Cancer Database was queried for all men with cT1 penile cancer from 2004 to 2015. Patients were categorized as cT1a or cT1b. Treatment was categorized as no treatment, local therapy (including penile sparing therapies), partial penectomy, or radical penectomy. Trends in treatment were analyzed over time and in correlation with stage and demographic variables. Stage and treatment type were evaluated in respect to pathological outcomes and survival. RESULTS: A total of 2,484 men were identified with cT1 penile cancer, 90.1% of which had cT1a disease. The most common treatments were local therapy for cT1a and partial penectomy for cT1b. Over the time period studied, use of local therapy decreased while use of partial or radical penectomy increased. Patients treated at low volume facilities were more likely to undergo no treatment (8.0% vs. 6.5% in high volume) or local therapy (49.9% vs. 41.5% in high volume, P < 0.001). Local therapy was associated with increased risk of positive margin (odds ratio 4.7, P < 0.001) and positive margin was associated with a trend toward decreased overall survival (P = 0.07). CONCLUSIONS: In the past decade, there has been decreased use of local therapy and increased use of partial or radical penectomy in cT1 penile cancer. Men treated at low volume facilities are more likely to be treated with local therapy which is associated with increased rates of positive margins and may also be associated with a trend toward decreased overall survival. Centralization of care in T1 penile cancer may lead to improved outcomes.

The Role of Immunotherapy in Urologic Cancers.

In recent decades, there has been significant growth in the understanding of the immune system and its role in cancer. The recent introduction of checkpoint inhibitors has drastically changed the treatment landscape of cancer as a whole. In this review, we discuss the major clinical developments of immunotherapy in urologic specific cancers, as well as address future directions in this field.

Robotic surgery does not affect upstaging of T1 renal masses.

Partial nephrectomy is the mainstay of treatment for localized kidney cancer. A proportion of patients are upstaged post-operatively to locally advanced disease (pT3a). We aimed to identify the incidence of upstaging to pT3a during partial nephrectomy and its relationship to a robotic approach. The National Cancer Database was queried for patients diagnosed with cT1M0 disease between 2010 and 2015 who underwent an open or robotic partial nephrectomy with final stage pT1-3a. Our primary outcome was rate of upstaging to pT3a in patients undergoing partial nephrectomy and secondary outcomes were stage migration, rate of positive margins, and overall survival (OS). The relationship between open and robotic surgery was examined. Logistical regression and Kaplan-Meier analyses were performed. Of 68,976 patients identified, 5.9% of patients were upstaged from cT1 to pT3a post-operatively. The incidence of upstaging to pT3a disease has increased from 5.7% in 2010 to 6.9% in 2015. Similarly, the proportion of patients undergoing a robotic approach is also increasing (31.6-64.4%); however, a robotic approach is not associated with pT3a upstaging on multivariable analysis. The probability of being upstaged was significantly proportional to increasing tumor size (OR 2.634-11.641, p < 0.05). pT3a disease was associated with a significant increase in positive margins (10.7% vs 5.0%, p < 0.001). Interestingly, pT3a patients with positive margin had worsened survival (5-year OS 75.5% vs 65.9%, p < 0.001). A robotic surgical approach to partial nephrectomy does not increase risk of upstaging to pT3a disease. Those who are upstaged have increased risk of positive margins and associated risk of decreased survival.

Chemotherapy increases survival and downstaging of upper tract urothelial cancer.

INTRODUCTION: To evaluate the overall survival and pathologic downstaging effect of neoadjuvant chemotherapy for upper tract urothelial cell carcinoma. MATERIALS AND METHODS: The National Cancer Database (NCDB) was queried for patients with stage II-IV upper tract urothelial cell carcinoma undergoing definitive surgical resection (nephroureterectomy) from 2004-2015. Patients with metastatic disease were excluded. Cohorts were stratified by receipt of neoadjuvant chemotherapy (NAC). Kaplan-Meier analysis and Cox regression were used to evaluate overall survival. Logistic regression was used to predict the odds of pathologic downstaging to non-invasive disease (< pT2). Propensity score matched analysis was performed between groups. RESULTS: A total of 3634 patients were identified with non-metastatic stage II-IV disease undergoing surgical resection; 3364 received no chemotherapy and 270 received NAC. Patients undergoing NAC had a 10.9% rate of downstaging to non-invasive disease (OR 6.35, p < 0.001). Moreover, on Kaplan-Meier analysis, median survival was 27.3 months and 44.8 months for no chemotherapy versus NAC, respectively (log-rank, p = 0.001). Cox regression for death also revealed benefits for receiving NAC (HR 0.67, p < 0.001). Findings were confirmed on propensity score matching (532 matched patients). After matching, Cox regression for death noted improvement with neoadjuvant as compared to no chemotherapy (HR 0.61, p < 0.001). CONCLUSION: Neoadjuvant chemotherapy increases likelihood of downstaging to non-invasive disease in patients with upper tract urothelial cell carcinoma. Chemotherapy also provides an overall survival benefit in patients undergoing nephroureterectomy.

Lymph node density for stratification of survival outcomes with node positive upper tract urothelial carcinoma.

INTRODUCTION: The use of lymph node density (LND) as a predictor of survival outcomes has been studied with urothelial carcinoma of the bladder. Similar results can be postulated to upper tract urothelial carcinoma (UTUC). This study aims to determine the overall survival of patients with lymph node positive UTUC based on LND, utilizing the National Cancer Database (NCDB). MATERIALS AND METHODS: Data was derived from NCDB Participant User Kidney Dataset using the histology code 'transitional cell carcinoma', utilizing pN+ patients from 2004-2015. LND was calculated as number of positive nodes divided by total number of nodes removed. Patients were stratified by traditional AJCC pN stage and compared to LND groups (< 30%, ≥ 30%). Primary outcome was overall survival. Kaplan-Meier and Cox regression analyses were performed. RESULTS: A total of 2049 patients were identified (pN1 = 1022, pN2 = 1027; LND < 30% = 370, ≥ 30% = 1679). Mean LND was 71%. Cox regression for mortality using pN stage was not significant (p = 0.11); however, Cox regression for mortality using LND group noted significantly worsened survival with LND ≥ 30% (HR 1.54, p = 0.001). Kaplan Meier analysis for overall survival at 2 years showed no difference between pN1 and pN2 stages (35.3% versus 34.1%; log rank p = 0.37). Kaplan Meier analysis for overall survival at 2 years revealed significant difference between LND groups (LND < 30%, 47.3% versus LND ≥ 30%, 32.0%; log rank p < 0.001). CONCLUSIONS: LND provides improved prognostic information regarding overall survival, compared to traditional AJCC pN staging. Future studies need to evaluate LND to improve prognostic understanding of lymph node positive UTUC.

Charlson comorbidity score is associated with readmission to the index operative hospital after radical cystectomy and correlates with 90-day mortality risk.

PURPOSE: Our objective was to determine perioperative variables associated with 30-day readmission to the index operative hospital after radical cystectomy for bladder cancer and subsequent survival outcomes. METHODS: Retrospective cohort study utilizing the United States National Cancer Database from 2004-2015. All clinical stages undergoing radical cystectomy were analyzed. Exclusion criteria included clinical suspicion of nodal disease, metastasis, or preoperative radiation therapy. Multivariable logistic regression was used for 30-day readmission risk to the index hospital. Kaplan-Meier analysis and multivariable Cox regressions were used for survival outcomes. RESULTS: 31,147 patients were identified and stratified by 30-day readmission (n = 2628) or no readmission (n = 28,519). Thirty-day readmission to the index surgery hospital was 8.4%. Groups were comparable in terms of age, gender, race, income, facility type, insurance, length of hospital stay, and pathologic stage. There were significantly more patients with higher Charlson comorbidity score in the readmission cohort. On logistic regression analysis, increasing Charlson score was the only predictor of 30-day readmission (OR 1.39-1.73, p < 0.001). The 90-day mortality rate was 7.2% overall (7.0% no readmission vs 9.9% 30-day readmission, p < 0.001). Cox regression analysis for mortality revealed increasing age (HR 1.04), higher Charlson score (HR 1.42-1.85), readmission within 30 days (HR 1.38) and pathologic stage pT ≥ 2 (HR 1.88-7.09, all p < 0.001) as independent predictors of 90-day mortality. CONCLUSIONS: Increasing comorbidity is a strong predictor of readmission to the index surgery hospital after radical cystectomy. Readmission is associated with worsened mortality at 90 days.

National Trends in the Utilization of Androgen Deprivation Therapy for Very Low Risk Prostate Cancer.

OBJECTIVE: To analyze national trends using the National Cancer Database (NCDB) in use of androgen deprivation therapy (ADT), outside of standard of care, in patients with very low risk prostate cancer. METHODS: We identified 52,797 men in the NCDB from 2010 to 2015 diagnosed with very low risk prostate cancer as defined (cT1cM0, PSA <10, Gleason ≤6, <3 biopsy cores positive). We evaluated the treatment trends and the proportion of men treated with ADT based on race, income, insurance status, treatment facility volume, and Charlson comorbidity. RESULTS: From 2010 to 2015, prevalence of primary ADT use in patients with very low risk prostate cancer remained 0.7%. Patients treated at low-volume facilities were more likely to receive primary ADT (hazard ratio [HR] 1.29, P <.001) as were black patients (HR 1.47, P <.001). When evaluated over time, the proportion of men treated with primary ADT who were white decreased while the proportion of men who were black increased. CONCLUSION: The use of primary ADT in men with very low risk prostate cancer has not changed over time, and may be over utilized, particularly among black men and those treated at low-volume facilities.

Squamous cell carcinoma of the bladder: poor response to neoadjuvant chemotherapy.

BACKGROUND: Squamous cell carcinoma (SCC) of the bladder is a rare, aggressive malignancy. Unlike urothelial cell carcinoma, SCC is resistant to chemotherapy and guidelines recommend radical cystectomy (RC) without neoadjuvant chemotherapy (NAC). We aimed to evaluate the current management and survival of patients with invasive SCC treated with or without NAC. METHODS: 671 patients with invasive SCC bladder cancer from 2004 to 2015 in the National Cancer Data Base were identified. Patients were stratified by treatment with RC alone or NAC prior to RC (NAC + RC). Survival analysis was performed with Kaplan-Meier and Cox regression. Secondary outcomes included length of stay and readmission. RESULTS: Of 671 patients, 92.8% were treated with RC alone and 7.2% with NAC + RC. Cox regression for mortality was performed including age, Charlson score, clinical stage, and NAC. Increased risk of mortality was noted with increasing age (OR 1.01, p = 0.023) and Charlson score of 1-3 (HR 1.58-1.68, p < 0.05). NAC did not confer survival advantage (HR 1.17, p = 0.46). On Kaplan-Meier analysis, the overall survival was equivalent (log-rank p = 0.804). Hospital stay and readmission were similar between RC and NAC + RC groups. CONCLUSIONS: Analysis of a national tumor registry suggests a lack of overall survival benefit for NAC with localized, muscle invasive SCC of the bladder. Further research directed at chemotherapy regimens for SCC is needed to optimize treatment and improve survival outcomes.

Trends in the treatment of clinical T1 renal cell carcinoma for octogenarians: Analysis of the National Cancer Database.

OBJECTIVE: Treatment of renal cell carcinoma has evolved with emphasis on nephron preservation for small renal masses. Our objective was to evaluate the proportions of treatment types for octogenarians with clinical stage 1 renal cell carcinoma. MATERIALS AND METHODS: The National Cancer Database was analyzed from 2004 to 2015. Patients with clinical stage 1, tumor size ≤ 7 cm, and age 80-89 years old were compared to a younger control arm of patients ≤ 70 years old. Treatment modality was categorized as radical nephrectomy (RN), partial nephrectomy (PN), percutaneous ablative therapy (PAT), and no treatment (NT). Primary outcome was treatment utilization over time using estimated annual percentage change (EAPC). Secondary outcomes included logistic regression for 30 day readmission after treatment and any definitive tumor treatment choice. RESULTS: 18,903 octogenarians were identified and compared to a control of 142,179 patients ≤ 70 years old. Overall, NT (36%) was the most common modality for octogenarians while PN (44.8%) was most common for the control arm. Using EAPC for octogenarians, we found increases for PAT (7.1%), PN (2.8%), and NT (1.6%) but a decrease for RN (-4.6%). EAPC for the younger cohort noted increases for PAT (6.8%), PN (5.4%), and NT (4.4%) but a decrease for RN (-5.5%). CONCLUSION: For octogenarians with stage 1 renal cell carcinoma, minimally invasive treatments are increasingly utilized, while RN is decreasing. Compared to a younger cohort, a greater proportion of octogenarians are receiving NT. These findings remain encouraging for appropriate treatment of localized disease in patients with advanced age.

Invasive non-urachal adenocarcinoma of the bladder: analysis of the National Cancer Database.

PURPOSE: To review the United States National Cancer Database (NCDB) from 2004 to 2015 and analyze survival outcomes of invasive non-urachal adenocarcinoma based on treatment modality. METHODS: The NCDB 2004-2015 bladder dataset was queried for adenocarcinoma histology, excluding urachal variant, and limited to patients with clinical stage T2-T4 disease. Treatment modality was categorized as no treatment, cystectomy (partial or radical), external beam radiation therapy (EBRT), or EBRT plus cystectomy. Our primary outcome was overall survival. Cox regression (CR) and Kaplan-Meier (KM) analysis were performed. RESULTS: 851 patients were identified with invasive (cT2-T4) adenocarcinoma of the bladder. Treatment modalities included 398 (47.8%) no treatment, 298 (35.8%) cystectomy, 124 (14.9%) EBRT, and 31 (3.7%) EBRT plus cystectomy. On KM analysis excluding those with metastatic disease, the 5-year survival was significantly better (p < 0.001) for patients who underwent cystectomy (39.6%), versus no treatment (21.0%), EBRT (18.6%), or EBRT plus cystectomy (26.9%) (log rank, p < 0.001). On CR for mortality, age (HR 1.030, p < 0.001), Charlson score 1 (HR 1.287, p = 0.034), cT4 (HR 1.768, p < 0.001), and receiving treatment at a low-volume center (HR 1.289, p = 0.026) were associated with worsened survival; however, cystectomy (HR 0.593, p < 0.001) was the only factor associated with improved survival. For those undergoing cystectomy, the mean length of stay was 8.5 days and the 30-day readmission rate was 7.0%. CONCLUSIONS: Invasive non-urachal adenocarcinoma of the bladder is a rare diagnosis. Survival benefits in patients without metastatic disease are seen only in those patients undergoing definitive surgery.