Symptomatic and functional recovery after transurethral resection of bladder tumor: Data from ecological momentary symptom assessment.

OBJECTIVES: To quantitatively describe the nature, severity, and duration of symptoms and functional impairment during recovery from transurethral resection of bladder tumors. MATERIALS AND METHODS: All patients scheduled for transurethral resection were approached for enrollment in a text-message based ecological momentary symptom assessment platform. Nine patients reported outcomes were measured 7 days before surgery and on postoperative days 1, 2, 3, 5, 7, 10, and 14 using a 5-point Likert scale. Self-reported degree of hematuria was collected using a visual scale. Clinical data was collected via retrospective chart review. RESULTS: A total of 159 patients were analyzed. Postoperative symptoms were overall mild, with the largest differences from baseline to postoperative day 1 seen in dysuria (median 0/5 vs. 3/5) and ability to work (median 5/5 vs. 4/5). Recovery was generally rapid, with 76% of patients reporting ≥4/5 agreement with the statement "I feel recovered from surgery" by postoperative day 2, although 15% of patients reported persistently lower levels of agreement on postoperative day 10 or 14. Patients undergoing larger resections (≥2cm) did take longer to return to baseline in multiple symptom domains, but the difference of medians vs. those undergoing smaller resections was less than 1 day across all domains. Multivariable analysis suggested that receiving perioperative intravesical chemotherapy was associated with longer time to recovery. 84% of patients reported clear yellow urine by postoperative day 3. CONCLUSION: In this population, hematuria and negative effects on quality of life resulting from transurethral resection of bladder tumors were generally mild and short-lived, although a small number of patients experienced longer recoveries.

Real-time estimation of nephron activity with a linear measurement system (RENAL-MS) predicts postoperative estimated glomerular filtration rate.

OBJECTIVE: To determine whether a simple point-of-care measurement system estimating renal parenchymal volume using tools ubiquitously available could be used to replace nuclear medicine renal scintigraphy (NMRS) in current clinical practice to predict estimated glomerular filtration rate (eGFR) after nephrectomy by estimating preoperative split renal function. PATIENTS AND METHODS: We performed a retrospective review of patients who underwent abdominal cross-sectional imaging (computed tomography/magnetic resonance imaging) and mercaptoacetyltriglycine (MAG3) NMRS prior to total nephrectomy at a single institution. We developed the real-time estimation of nephron activity with a linear measurement system (RENAL-MS) method of estimating postoperative renal function via the following technique: renal parenchymal volume of the removed kidney relative to the remaining kidney was estimated as the product of renal length and the average of six renal parenchymal thickness measurements. The utility of this value was compared to the utility of the split renal function measured by MAG3 for prediction of eGFR and new onset Stage 3 chronic kidney disease (CKD) at ≥90 days after nephrectomy using uni- and multivariate linear and logistic regression. RESULTS: A total of 57 patients met the study criteria. The median (interquartile range [IQR]) age was 69 (61-80) years. The median (IQR) pre- and postoperative eGFR was 74 (IQR 58-90) and 46 (35-62) mL/min/1.73 m2 , respectively. [Correction added on 29 December 2023, after first online publication: The data numbers in the preceding sentence have been corrected.] Correlations between actual and predicted postoperative eGFR were similar whether the RENAL-MS or NMRS methods were used, with correlation using RENAL-MS being slightly numerically but not statistically superior (R = 0.82 and 0.76; P = 0.138). Receiver operating characteristic curve analysis using logistic regression estimates incorporating age, sex, and preoperative creatinine to predict postoperative Stage 3 CKD were similar between RENAL-MS and NMRS (area under the curve 0.93 vs. 0.97). [Correction added on 29 December 2023, after first online publication: The data numbers in the preceding sentence have been corrected.] CONCLUSION: A point-of-care tool to estimate renal parenchymal volume (RENAL-MS) performed equally as well as NMRS to predict postoperative eGFR and de novo Stage 3 CKD after nephrectomy in our population, suggesting NMRS may not be necessary in this setting.

Female sexual function evaluation and intraoperative vaginal reconstruction in bladder cancer.

RC significantly negatively impacts sexual function (SF) in both men and women. While significant research resources have been allocated to examine the deleterious effects of post prostatectomy erectile dysfunction, little attention has been directed towards female sexual function and organ preservation post cystectomy. These academic shortcomings often result in poor provider awareness and inadequate preoperative assessment. As such, it is crucial for all providers involved in female RC care to understand the necessary and available tools for preoperative evaluation, in addition to the anatomic and reconstructive techniques. This review aims to summarize the current preoperative evaluation and available tools of SF assessment and describe in detail the varying operative techniques in the preservation or restoration of SF in women after RC. The review explores the intricacies of preoperative evaluation tools, and intraoperative techniques for organ- and nerve-sparing during radical cystectomy in females. Particular emphasis on vaginal reconstruction after partial or complete resection is provided, including split-thickness skin (STF) graft vaginoplasy, pedicled flaps, myocutaneous flaps and use of bowel segments. In conclusion, this narrative review highlights the importance of understanding anatomic considerations and nerve-sparing strategies in promoting postoperative SF and quality of life. Furthermore, the review describes the advantages and limitations of each organ- and nerve-sparing technique and their impact on sexual function and overall well-being.

Clinical Performance of Technetium-99m-Sestamibi SPECT/CT Imaging in Differentiating Oncocytic Tumors From Renal Cell Carcinoma in Routine Clinical Practice.

PURPOSE: Technetium-99m-sestamibi single-photon emission CT/x-ray CT is an emerging clinical tool to differentiate oncocytic tumors from renal cell carcinomas. We report data from a large institutional cohort of patients who underwent technetium-99m-sestamibi scans during evaluation of renal masses. MATERIALS AND METHODS: Patients who underwent technetium-99m-sestamibi single-photon emission CT/x-ray CT between February 2020 and December 2021 were included in the analysis. Scans were defined as "hot" for oncocytic tumor when technetium-99m-sestamibi uptake was qualitatively equivalent or higher between the mass of interest and normal renal parenchyma, suggesting oncocytoma, hybrid oncocytic/chromophobe tumor, or chromophobe renal cell carcinoma. Demographic, pathological, and management strategy data were compared between "hot" and "cold" scans. For individuals who underwent diagnostic biopsy or extirpative procedures, the concordance between radiological findings and pathology was indexed. RESULTS: A total of 71 patients (with 88 masses) underwent technetium-99m-sestamibi imaging with 60 (84.5%) patients having at least 1 "cold" mass on imaging and 11 (15.5%) patients exhibiting only "hot" masses. Pathology was available for 7 "hot" masses, with 1 biopsy specimen (14.3%) being discordant (clear cell renal cell carcinoma). Five patients with "cold" masses underwent biopsy. Out of 5 biopsied masses, 4 (80%) were discordant oncocytomas. Of the extirpated specimens, 35/40 (87.5%) harbored renal cell carcinoma and 5/40 (12.5%) yielded discordant oncocytomas. In sum, 20% of pathologically sampled masses that were "cold" on technetium-99m-sestamibi imaging still harbored oncocytoma/hybrid oncocytic/chromophobe tumor/chromophobe renal cell carcinoma. CONCLUSIONS: Further work is needed to define utility of technetium-99m-sestamibi in real-world clinical practice. Our data suggest this imaging strategy is not yet ready to replace biopsy.

Pathological and Clinical Outcomes in a Large Surveillance and Intervention Cohort of Radiographically Cystic Renal Masses.

PURPOSE: We evaluated oncologic risks in a large cohort of patients with radiographic cystic renal masses who underwent active surveillance or intervention. MATERIALS AND METHODS: A single-institutional database of 4,340 kidney lesions managed with either active surveillance or intervention between 2000-2020 was queried for radiographically cystic renal masses. Association of radiographic tumor characteristics and high-grade pathology was evaluated. RESULTS: We identified 387 radiographically confirmed cystic lesions in 367 patients. Of these, 247 were resected (n=240) or ablated (n=7; n=247, 203 immediate vs 44 delayed intervention). Pathologically, 23% (n=56) demonstrated high-grade pathology. Cystic features were explicitly described by pathology in only 18% (n=33) of all lesions and in 7% (n=4) of high-grade lesions. Of the intervention cohort, African American race, male gender, and Bosniak score were associated with high-grade pathology (P < .05). On active surveillance (n=184), Bosniak IV lesions demonstrated faster growth rates than IIF and III lesions (2.7 vs 0.6 and 0.5 mm/y, P ≤ .001); however, growth rates were not associated with high-grade pathology (P = .5). No difference in cancer-specific survival was identified when comparing intervention vs active surveillance at 5 years (99% vs 100%, P = .2). No difference in recurrence was observed between immediate intervention vs delayed intervention (P > .9). CONCLUSIONS: A disconnect between "cystic" designation on imaging and pathology exists for renal lesions. Over 80% of radiographic Bosniak cystic lesions are not described as "cystic" on pathology reports. More than 1 in 5 resected cystic renal lesions demonstrated high-grade disease. Despite this finding, judiciously managed active surveillance ± delayed intervention is a safe and effective management option for most radiographic cystic renal masses.

No difference in renal function outcomes for patients with oncocytoma managed with active surveillance vs. partial nephrectomy.

OBJECTIVES: To investigate the difference in renal function outcomes for patients with oncocytomas undergoing active surveillance (AS) vs. partial nephrectomy (PN). METHODS: We reviewed our institutional database for patients with biopsy/surgically confirmed oncocytoma from 2000-2020. The primary outcome was to assess for differences in renal function outcomes in patients undergoing AS vs. PN. We fit two generalized estimating equation (GEE) with an interaction term between follow up time and management strategy to predict 1) mean eGFR for patients managed with AS and PN and 2) the probability of progression to CKD stage III or greater. RESULTS: We identified 114 eligible patients, of which 32 were managed with AS. Median follow-up was 21 months vs. 44 months for PN vs. AS patients. AS patients tended to be older (median: 72 years vs. 65 years, P<0.001) and have lower baseline renal function (median: eGFR: 71 mL/min/1.73m2 vs. 82 mL/min/1.73m2, P<0.001) compared with PN patients. Renal mass size from baseline imaging was similar between patients undergoing PN vs. AS (2.8 cm vs. 2.9 cm, P=0.634). For patients undergoing PN vs. AS, there was not a significant difference in predicted longitudinal eGFR (-0.079, 95% CI -0.18-0.023, P=0.129) or predicted probability of progression to CKD stage III or greater (OR: 0.61, 95% CI: 0.16-2.33, P=0.47). CONCLUSIONS: In our institutional dataset, patients undergoing AS or PN with an oncocytoma had similar long-term renal function outcomes. Given similar renal function outcomes in patients undergoing AS and PN, surgery should remain reserved for select patients with oncocytomas.

Association of tumor size and surgical approach with oncological outcomes and overall survival in patients with adrenocortical carcinoma.

OBJECTIVES: To investigate the association of surgical approach with outcomes in patients with adrenocortical carcinomas smaller and larger than 6 cm in size. METHODS: We reviewed the national cancer database for patients undergoing minimally invasive adrenalectomy (MIA) and open adrenalectomy (OA) from 2010 to 2017. To adjust for differences between patients undergoing MIA and OA, we performed propensity score matching within each size strata of ≤6 cm, 6.1 to 10 cm, and 10.1 to 20 cm. We fit generalized estmiating equations with a logit link function to assess for the association of surgical approach with positive surgical margins and a Cox proportional hazards model to assess for the association of surgical approach with overall survival. RESULTS: We identified 364 patients that underwent MIA (182) and OA (182) in the matched cohort.  We noted 21% and 18% of patients undergoing MIA and OA had a positive surgical margin, respectively. We did not identify a significant association between surgical approach and positive surgical margins in the cohort as a whole or within each of strata. Furthermore, we did not appreciate a significant association between surgical approach and overall survival in the cohort as a whole or within each size strata. CONCLUSION: In the National Cancer Database, patients undergoing MIA had similar positive surgical margins and overall survival compared with OA for masses ≤6 cm, 6.1 to 10cm, and >10 cm in size. Patients undergoing MIA should be carefully selected with surgical oncologic integrity being the primary determinants of surgical approach.

Association of Surgical Approach With Treatment Burden, Oncological Effectiveness, and Perioperative Morbidity in Adrenocortical Carcinoma.

MICROABSTRACT: In the National Cancer Database (NCDB), patients treated with minimally invasive adrenalectomy (MIA) for adrenocortical carcinoma (ACC) had similar oncological outcomes and cumulative treatment burden with less morbidity compared with open adrenalectomy (OA). Although OA remains the standard of care for adrenal lesions concerninge for malignancy, MIA in appropriately selected patients may offer equivalent oncological outcomes. INTRODUCTION/BACKGROUND: We investigated the cumulative treatment burden, oncological effectiveness, and perioperative morbidity in patients undergoing MIA compared with (OA) for patients with ACC. PATIENTS AND METHODS: We reviewed the NCDB for patients undergoing surgical resection (MIA vs. OA) for ACC from 2010 to 2017. Inverse probability of treatment weighted logistic regression, negative binomial, and Cox proportional hazards models were fit to assess for an association of surgical approach with cumulative treatment burden (any adjuvant therapy, radiation therapy [RT], and systemic therapy), oncological effectiveness (positive surgical margins [PSM], lymph node yield [LNY], and overall survival [OS]), and perioperative morbidity (length of stay [LOS] and readmission) as appropriate. RESULTS: We identified 776 patients that underwent adrenalectomy for ACC, of which 307 underwent MIA. We noted patients with larger tumors (OR 0.82, 95% CI 0.78-0.86, P < .001) were less likely to have MIA prior to IPTW. We did not appreciate a significant association of MIA with cumulative treatment burden or the use of any adjuvant therapy (OR 0.85, 95% CI 0.60-1.21, P = .375), adjuvant RT (OR 0.94, 95% CI 0.59-1.50, P = .801), or adjuvant systemic therapy (OR 0.84, 95% CI 0.58-1.21, P = .352). Patients undergoing MIA had similar oncological effectiveness of surgery and OS when compared with patients which underwent OA. Patients that underwent MIA had a significantly shorter LOS (IRR: 0.74, 95% CI 0.62-0.88, P = .001) and lower odds of readmission (OR 0.46, 95% CI 0.23-0.91, P = .026). CONCLUSIONS: Although the standard of care for adrenal lesions suspicious for ACC remains OA, in appropriately selected patients, MIA may offer similar oncological effectiveness and cumulative treatment burden, with less morbidity, than OA.

The Role of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma: A Real-World Multi-Institutional Analysis.

PURPOSE: The role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) was challenged by the results of the CARMENA trial. Here we evaluate the role of CN in mRCC patients, including those receiving modern therapies. MATERIALS AND METHODS: We included patients with synchronous mRCC between 2011-2020 from the de-identified nationwide Flatiron Health database. We evaluated 3 groups: systemic therapy alone, CN followed by systemic therapy (up-front CN [uCN]) and systemic therapy followed by CN (deferred CN [dCN]). The primary outcome was median overall survival (mOS) in patients receiving systemic therapy alone vs uCN. Secondary outcome was overall survival in patients receiving uCN vs dCN. First-treatment, landmark and time-varying covariate analyses were conducted to overcome immortal time bias. Weighted Kaplan-Meier curves, log-rank tests and Cox proportional hazards regressions were used to assess the effect of therapy on survival. RESULTS: Of 1,910 patients with mRCC, 972 (57%) received systemic therapy, 605 (32%) received uCN, 142 (8%) dCN and 191 (10%) CN alone; 433 (23%) patients received immunotherapy-based therapy. The adjusted mOS was significantly improved in first-treatment, landmark and time-varying covariate analysis (mOS 26.6 vs 14.6 months, 36.3 vs 21.1 months and 26.1 vs 12.2 months, respectively) in patients undergoing CN. Among patients receiving CN and systemic therapy, the timing of systemic therapy relative to CN was not significantly related to overall survival (HR=1.0, 95% CI 0.76-1.32, p=0.99). CONCLUSIONS: Our findings support an oncologic role for CN in select mRCC patients. In patients receiving both CN and systemic therapy, the survival benefit compared to systemic alone was similar for up-front and deferred CN.

Safety of neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer and malignant ureteric obstruction.

OBJECTIVES: To determine whether patients with carcinoma invading bladder muscle (MIBC) and ureteric obstruction can safely receive cisplatin-based neoadjuvant chemotherapy (C-NAC), and to determine whether such patients require relief of obstruction with a ureteric stent or percutaneous nephrostomy prior to beginning C-NAC. PATIENTS AND METHODS: We performed a single-institution retrospective analysis of MIBC patients receiving C-NAC and falling into three groups: no ureteric obstruction (NO); relieved ureteric obstruction (RO); and unrelieved ureteric obstruction (URO). To address whether patients with obstruction can safely receive C-NAC, we compared patients with NO to those with RO, with the primary outcome of premature chemotherapy discontinuation. To investigate whether patients with obstruction should have the obstruction relieved prior to NAC, we compared RO to URO patients using a primary composite outcome of grade ≥ 3 adverse events, premature chemotherapy discontinuation, dose reduction, or dose interruption. The primary outcomes were compared using multivariable logistic regression. Sensitivity analyses were performed for the RO vs URO comparison, in which patients with only mild degrees of obstruction were excluded from the URO group. RESULTS: A total of 193 patients with NO, 49 with RO, and 35 with URO were analysed. There were no statistically significant differences between those with NO and those with RO in chemotherapy discontinuation (15% vs 22%; P = 0.3) or any secondary outcome. There was no statistically significant difference between those with RO and URO in the primary composite outcome (51% vs 53%; P = 1) or any secondary outcome. CONCLUSION: Patients with ureteric obstruction can safely receive C-NAC. Relief of obstruction was not associated with increased safety of C-NAC delivery.

Harnessing choice architecture in urologic practice: Implementation of an opioid-sparing protocol grounded in cognitive behavioral theory.

PURPOSE: Opioids are prescribed excessively following surgery. As many urologic oncology procedures are performed minimally invasively, an opportunity exists to push forward initiatives to minimize postoperative opioid use. MATERIALS AND METHODS: A quality improvement initiative to reduce inpatient opioid prescribing was launched at a tertiary cancer center. In Phase I (December 2019-July 2020), providers were instructed to start standing acetaminophen. In Phase II (beginning August 2020), education was provided to the entire care team and ordersets were modified to an opioid sparing protocol (OSP). We analyzed the proportion of minimally invasive surgery (MIS) prostatectomy and nephrectomy patients that adhered to an OSP during each phase and compared them to controls from the preceding 2 years. RESULTS: A total of 303, 153, and 839 patients underwent MIS during the Phase I, Phase II, and control periods respectively. The proportion of patients adhering to an OSP increased from 16% at the beginning of Phase I to 76% at the end of Phase II (p-trend < 0.001). The median total oral morphine equivalents for oral opioids declined from 20 mg and 40 mg at baseline for prostatectomy and nephrectomy patients respectively to 0 mg for both groups (p-trends < 0.001). Multivariable analysis found that patients received 22% and 81% less oral morphine equivalents during Phase I and II respectively compared to the control period (P < 0.001). CONCLUSIONS: Adherence to an OSP is most effective when initiatives incorporate the entire team and are supported by nudge theory-based structural changes. Using these strategies, most patients following urologic MIS can dramatically reduce opioid use postoperatively.

Oncologic Outcomes of cT1 and cT2 Micropapillary Variant Compared with cT1 and cT2 Conventional Urothelial Carcinoma Treated with Radical Cystectomy.

INTRODUCTION: Our objective was to estimate the difference in outcomes for patients with clinical T stage 1 (cT1) and 2 (cT2) micropapillary (MPBC) and urothelial carcinoma (UCBC) bladder cancer treated with radical cystectomy (RC). METHODS: We reviewed the National Cancer Database for patients with cT1/2N0M0 MPBC and UCBC treated with RC from 2004-2016. Patients were classified by cT stage and histology. Outcomes of interest included upstaging to advanced pathological stage (pT3/4), pathologically node positive disease (pN+), and overall survival (OS). The Kaplan-Meier method was used to estimate 5-year OS probability. Multivariable logistic regression models were fit to test for an association between cT stage and histology with outcomes. RESULTS: We identified 23,871 patients, of whom 384 had MPBC and 23,487 had UCBC. More patients with cT1 and cT2 MPBC had advanced pathological stage and pN+ (cT1: 31% and 34%; cT2: 44% and 60%, respectively) compared with cT1 and cT2 UCBC (cT1: 18% and 14%; cT2: 27% and 24%, respectively). Compared with cT2 UCBC, patients with cT1 MPBC had similar odds of advanced pathological stage (OR: 0.96, 95% CI: 0.63-1.45, p=0.837) and increased odds of pN+ (OR: 1.62, 95% CI: 1.03-2.56, p=0.038). Five-year OS estimates for cT1 MPBC and UCBC were similar (58% and 60%, respectively) while cT2 MPBC had worse OS than cT2 UCBC (33% and 45%, respectively). CONCLUSIONS: In a cohort of patients undergoing RC, cT1/2 MPBC had worse outcomes than cT1/2 UCBC. Patients and surgeons should consider aggressive therapies for patients with cT1 MPBC due to the risk of inferior outcomes associated with cT2 MPBC disease.

Feasibility and Outcomes of Renal Mass Biopsy for Anatomically Complex Renal Tumors.

OBJECTIVE: To compare the feasibility and outcomes of renal mass biopsies (RMB) of anatomically complex vs non-complex renal masses. METHODS: Our institutional renal tumor database was queried for patients who underwent RMB between 2005 and 2019 and with available nephrometry score. Complex masses were: (1) small (<2 cm), (2) entirely endophytic (nephrometry E=3), (3) hilar (h) or (4) partially endophytic (E=2) and anterior. Demographic and pathologic data were compared. Biopsies were deemed adequate if they resulted in a diagnosis. Concordance with surgical pathology was assessed. These were both presented using proportions. Factors associated with biopsy outcomes were identified using multivariable logistic regression. RMB sensitivity and specificity were calculated using contingency methods. RESULTS: A total of 306 RBMs were included, 179 complex and 127 non-complex. A total of 199 (65%) had an extirpative procedure. Complex lesions were less likely to have an adequate biopsy (89% vs 96%, P = .03), and to be concordant with final surgical pathology from an oncologic standpoint (89% vs 97%, P = .03). There was no significant difference in concordance of histology (76% vs 86%, P = .10) or grade (48 vs 51%, P = .66). On multivariable analyses, only male gender was associated with biopsy adequacy (OR 3.31, 95% CI 1.28-8.55, P = .01). Our overall sensitivity was 93%, specificity 93%, and accuracy 93%. There were no significant differences over time in biopsy outcomes during the study period. CONCLUSION: RMB of complex lesions is associated with excellent diagnostic yield, albeit lower than non-complex lesions. RMB should not be deferred in cases of anatomically complex lesions where additional data could improve clinical decision-making.

Renal mass biopsy: A strategy to reduce associated costs and morbidity when managing localized renal masses.

INTRODUCTION AND OBJECTIVES: Renal mass biopsy (RMB) has not been widely adopted in evaluating small renal mass due to concerns for safety, efficacy, and its perceived lack of consequence on management decisions. We assess the potential cost savings and morbidity avoidance of routine RMB on cT1 renal masses undergoing robotic-assisted partial nephrectomy (RAPN). METHODS: We identified n = 920 consecutive RAPN pT1 renal masses and n = 429 consecutive RMBs for cT1 renal masses over 12 years. Using a novel pathological-based risk classification system for cT1 renal masses, we evaluated the morbidity and costs of our RAPN and RMB cohorts. We then define four clinical scenarios where RMB could potentially delay and/or avoid intervention in our pT1 RAPN cohort and model potential complications prevented and cost savings utilizing common clinical scenarios. RESULTS: Using our risk stratification system in RAPN patients, final histology was classified as benign in n=174 (18.9%) cases, very low-risk (n = 62 [7%]), low-risk (n = 383 [42%]), and high-risk (n = 301 [33%]), respectively. We identified n = 116 (12.6%) Clavien graded peri-operative complications. In our RMB patients, 120 (27.9%), 17 (3.9%), 240 (55.9%), 52(12.1%) were benign, very low, low and high-risk tumors. The median total direct cost for RAPN was $6955/case compared to $1312/case for RMB. If we established a primary goal to avoid immediate extirpative surgery in benign renal tumors, in the elderly (>70 y) with very low-risk tumors and/or those with high renal functional risks (≥ CKD3b), or competing risks (ASA ≥ 3), RMB could have reduced direct costs by approximately 20% and avoided n = 39 Clavien graded complications, seven readmissions, three transfusions, and two returns to the OR. With the additional cost of performing RMB on those not initially biopsied, the net cost saving would be approximately $1.2 million with minimal added complications while still treating high-risk tumors. CONCLUSIONS: Routine RMB before intervention results in cost-saving and complication avoidance. Given the limitations of biopsy, shared decision-making is mandatory. Biopsy should be considered prior to intervention in at-risk populations.

Identification of oncological characteristics associated with improved overall survival in patients with adrenocortical carcinoma treated with adjuvant radiation therapy: Insights from the National Cancer Database.

OBJECTIVES: To test for an association between oncological risk factors and overall survival in patients with non-metastatic adrenocortical carcinoma treated with adjuvant radiation therapy at high-risk for recurrence per NCCN guidelines. MATERIALS AND METHODS: We analyzed data from patients undergoing surgical resection with or without aRT in the NCDB from 2004 to 2017. A multivariable Cox proportional hazards model was fit to assess for an association of aRT and OS. To determine whether aRT was associated with improved OS in patients with specific NCCN risk factors, we fit three multivariable Cox proportional hazard models with an interaction term between NCCN risk factors and the use of aRT. RESULTS: We identified 1,433 patients treated surgically for adrenocortical carcinoma with at least one risk factor. 259 patients received adjuvant radiation therapy (18%) while 1,174 (82%) patients did not. After adjustment, we noted a significant association between adjuvant radiation therapy and overall survival in the entire cohort in the multivariable Cox proportional hazards model (HR 0.68, 95% CI 0.55-0.85, P = 0.001). Adjuvant radiation therapy was associated with increased overall survival in patients with positive surgical margins (HR 0.47, 95% CI 0.35-0.65, P < 0.001), large tumor size ≥6 cm (HR 0.69, 95% CI 0.55-0.87, P = 0.002), and high-grade disease (HR 0.61, 95% CI 0.37-0.99, P = 0.046). CONCLUSIONS: Patients with ACC at high-risk for recurrence were associated with improved overall survival when treated with adjuvant radiation therapy. These data may help identify which patients should consider aRT after resection of clinically localized ACC.

Cystoscopy and Systematic Bladder Tissue Sampling in Predicting pT0 Bladder Cancer: A Prospective Trial.

PURPOSE: Concern for discordance between clinical staging and final pathology drives current management of patients deemed appropriate candidates for radical cystectomy. Therefore, we set out to prospectively investigate reliability and shortcomings of cystoscopic evaluation in radical cystectomy candidates. MATERIALS AND METHODS: Patients undergoing radical cystectomy for urothelial carcinoma were enrolled in a prospective single-arm study to evaluate reliability of Systematic Endoscopic Evaluation in predicting pT0 urothelial carcinoma (NCT02968732). Systematic Endoscopic Evaluation consisted of cystoscopy and tissue sampling at the time of radical cystectomy. Systematic Endoscopic Evaluation results were compared to radical cystectomy pathology. The primary end point was the negative predictive value of Systematic Endoscopic Evaluation findings in predicting radical cystectomy pathology. RESULTS: A total of 61 patients underwent Systematic Endoscopic Evaluation and radical cystectomy. Indications included muscle invasive bladder cancer in 42 (68.9%) and high risk nonmuscle invasive bladder cancer in 19 (31.1%). In all, 38 (62.3%, 90.5% of patients with muscle invasive bladder cancer) received neoadjuvant chemotherapy. On Systematic Endoscopic Evaluation, 31 (50.8%) patients demonstrated no visual nor biopsy-based evidence of disease (seeT0), yet 16/31 (51.6%) harbored residual disease (>pT0), including 8 (8/31, 25.8%) with residual ≥pT2 disease upon radical cystectomy. The negative predictive value of Systematic Endoscopic Evaluation predicting a pT0 bladder was 48.4% (CI 30.2-66.9), which was below our prespecified hypothesis. Therefore, the trial was stopped for futility. CONCLUSIONS: Approximately 1 of 4 patients with seeT0 at the time of radical cystectomy harbored residual muscle invasive bladder cancer. These prospective data definitively confirm major limitations of endoscopic assessment for pT0 bladder cancer. Future work should focus on novel imaging and biomarker strategies to optimize evaluations before radical cystectomy for improved decision making regarding bladder preservation.

Sporadic Angiomyolipomas Growth Kinetics While on Everolimus: Results of a Phase II Trial.

PURPOSE: Everolimus decreases tumor volume of renal angiomyolipomas in patients with tuberous sclerosis. No prospective data are available regarding the effect of everolimus on the growth kinetics in patients with sporadic angiomyolipomas. We sought to determine the safety and efficacy of everolimus in the volumetric reduction of sporadic angiomyolipomas. MATERIALS AND METHODS: This multi-institutional, prospective, phase II trial, enrolled patients with 3 cm or larger sporadic angiomyolipomas who were candidates for surgical resection or percutaneous angioembolization. Patients received 10 mg everolimus daily for 4 planned 28-day cycles. Response was defined as a 25% or greater volumetric reduction of patient angiomyolipoma. Baseline, 4, 6 and 12-month volumetric analyses were performed using magnetic resonance imaging. Everolimus was discontinued in those with less than 25% volumetric reduction after 4 cycles. Those with 25% or greater volumetric reduction received 2 additional cycles. The primary outcomes were the efficacy of everolimus in the volumetric reduction of angiomyolipomas by 25% or more, and the safety and tolerability of everolimus. RESULTS: Overall 20 patients were enrolled at 5 centers. Of these patients 11 (55%) completed 4 cycles and 7 (35%) completed 6 cycles. Efficacy was demonstrated, with 10 of 18 (55.6%) patients exhibiting a 25% or greater reduction in tumor volume at 4 months (median 58.5%) and 10 of 14 (71.4%) patients exhibiting a 25% or greater reduction in tumor volume at 6 months (median 58.2%). Four (20%) patients were withdrawn due to protocol defined toxicities and 8 (40%) self-withdrew from the study due to side effects. CONCLUSIONS: Everolimus was effective in causing volumetric reduction of angiomyolipomas by 25% or greater in most patients but was associated with a high rate of treatment discontinuation.

Defects in DNA Repair Genes Confer Improved Long-term Survival after Cisplatin-based Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer.

Cisplatin-based neoadjuvant chemotherapy (NAC) has demonstrated an overall survival (OS) benefit in muscle-invasive bladder cancer (MIBC). However, only a subset of patients (25-50%) have a pathologic complete response at cystectomy. Using a cohort of 58 patients from two phase 2 trials, our group previously reported that mutations in the ATM, RB1, and FANCC genes correlate with complete response to cisplatin-based NAC, and consequently improve OS and disease-specific survival (DSS). These trials enrolled patients with T2-4 (N0 or N1) MIBC and treated them with accelerated/dose-dense NAC with methotrexate, vinblastine, adriamycin, and cisplatin, or gemcitabine and cisplatin, with a plan for curative cystectomy. Updated long-term follow-up (median 74 mo) shows that significantly greater OS and DSS was maintained for patients with ATM, RB1, or FANCC mutations. The 5-yr survival rate for patients with at least one mutation was 85%, compared to 45% for patients without a mutation. On the basis of the associations with response and long-term OS and DSS, we propose that these alterations may be useful as predictive biomarkers to allow clinicians to prioritize patients who are most likely to benefit from NAC before radical cystectomy. PATIENT SUMMARY: In this report we looked at outcomes for patients with muscle-invasive bladder cancer treated with cisplatin-based chemotherapy before surgery (neoadjuvant) who had mutations in a set of DNA damage repair genes (ATM, RB1, FANCC) compared to those who did not. We found that patients who had at least one mutation in one of these genes survived longer after receiving cisplatin chemotherapy before surgery than patients who did not.

Bacillus Calmette-Guérin Packaged for Percutaneous Vaccination Can Be Safely Used for Intravesical Instillation in Patients with Urothelial Carcinoma of the Bladder.

INTRODUCTION: Bacillus Calmette-Guérin production is limited worldwide with stuttering shortages affecting patient access. Our institution received 50 vials of bacillus Calmette-Guérin labeled for percutaneous administration, and upon discussion with our clinical team and approval by the Pharmacy and Therapeutics Committee we used the percutaneous formulation in place of the intravesical formulation. We report our experience. METHODS: Between February and April 2019 patients were treated with a third of a vial dose either with percutaneous or intravesical bacillus Calmette-Guérin. American Urological Association Symptom Score and Quality of Life survey and an additional 6-question survey (querying presence of suprapubic pain, hematuria, fevers, malaise, skin rashes, testicular/groin pain) were administered. Statistical analyses comparing the 2 groups were performed with SPSS version 22 software. RESULTS: A total of 30 patients with 73 intravesical instillations were evaluated with 34 patients receiving intravesical and 39 percutaneous bacillus Calmette-Guérin. We found no significant differences when comparing intravesical vs percutaneous bacillus Calmette-Guérin groups in terms of American Urological Association Symptom Score (6.1 vs 6.9, p=0.177), Quality of Life score (1.3 vs 1.7, p=0.132), fevers (2.9% vs 0%, p=0.300), hematuria (14.7% vs 2.8%, p=0.075), suprapubic pain (10.1% vs 4.3%, p=0.129), skin rashes (1.4% vs 0%, p=0.307) and feeling of general fatigue and malaise (15.7% vs 8.6%, p=0.126). CONCLUSIONS: Intravesical instillation of percutaneous bacillus Calmette-Guérin appears to be a safe alternative to intravesical bacillus Calmette-Guérin during times of shortage. Development of additional strains, use of alternative intravesical therapies and incentivizing bacillus Calmette-Guérin production through policy change and/or alternative funding may also help avoid bacillus Calmette-Guérin supply shortages in the future.