Brian Shuch

383 Background: 2-(¹⁸F) fluoro-2 deoxy-D-glucose (FDG) PET/CT is a useful tool in the staging of malignancies. In patients with kidney cancer, the role of FDG is limited in those with clear-cell histology and remains to be evaluated with other subtypes. Kidney cancer associated with hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is characterized by a defect in the Krebs cycle rendering these tumors highly dependent on aerobic glycolysis (the ‘Warburg effect’) with high glucose uptake to fulfill their energy requirements; we hypothesized that FDG PET/CT may have excellent sensitivity for staging in this condition. Methods: We retrospectively reviewed patients with HLRCC kidney cancer that underwent FDG PET/CT in conjunction with anatomic imaging at our institution. The ability of FDG PET/CT to detect malignant lesions (defined using pathologic or radiologic criteria) was evaluated. Results: A total of 30 patients underwent 42 PET /CTs. Conventional imaging identified a total of 107 lesions. Both patient and lesion-based analyses were performed. A total of 90 lesions, including ten renal lesions, were classified as malignant. 76 of 80 extra-renal lesions were correctly identified as malignant by PET/CT (sensitivity, 95%, CI 88-98%). In contrast, only 4 of 10 renal lesions were correctly identified as malignant (sensitivity, 40%, CI 17-69%). 11 of 12 histologically confirmed extra-renal lesions were PET avid (sensitivity, 92%, CI-64-98%). 10 of 12 (83%) benign lesions associated with HLRCC including uterine/cutaneous leiomyomas and adrenal nodules were PET avid. In a patient based analysis, all 18 patients with extra-renal spread of kidney cancer were correctly identified (sensitivity 100%, CI 82-100%). Conclusions: FDG PET/CT is a highly sensitive diagnostic modality for identifying metastatic kidney cancer associated with HLRCC. Prospective studies evaluating the utility of PET/CT imaging to characterize response to systemic therapy are currently underway.

363 Background: Partial (PN) and radical (RN) nephrectomy are treatments for the small renal mass. PN is considered the gold standard, as it may protect against renal dysfunction compared to RN. As active surveillance is emerging as a possible strategy, it is essential to understand the adverse health outcomes associated with both interventions. Methods: A retrospective, case-controlled series was performed using the Surveillance, Epidemiology, and End Results-Medicare dataset. Individuals treated with PN or RN for ≤4 cm non-metastatic, renal cell carcinoma (RCC) were compared to two control groups (non-muscle invasive bladder cancer [BCC] and non-cancer patients [NCC]). A Greedy Algorithm matched surgical groups (1:1) to controls by demographics and comorbidity. Medical claims >30 days after treatment were examined for renal, cardiovascular, and secondary cancer events. Results: Patients undergoing PN (1,436) and RN (4,247) were matched to controls and no significant differences were noted in key variables. All cancer groups had 10-year cancer-specific survival >95%. The time to event model demonstrated an increased risk of renal events for both treatments. Compared to BCC and NCC, RN hazard ratios were 2.415 (p < 0.0001) and 6.211 (p < 0.0001), respectively, while PN hazard ratios were 1.513 (p < 0.0001) and 4.926 (p < 0.0001), respectively. Secondary cancers were increased for both PN and RN compared to both control groups (p < 0.0001). Cardiovascular events were increased for both PN and RN compared to NCC (p < 0.0001), but this failed to reach significance when either group was compared to BCC controls. Conclusions: RCC patients treated with PN and RN are at significant risk of subsequent adverse health outcomes. When compared to RN, PN may have better renal outcome; however, when compared to controls, both options significantly increase renal events. The increase in secondary cancers and cardiovascular events with PN and RN is concerning and requires further investigation. As active surveillance is an emerging strategy, it may be time to rethink our current treatment paradigm for the small renal mass.

342 Background: Approximately 1-4% of renal cell carcinoma (RCC) is hereditary. No guidelines exist for patient selection for RCC genetic counseling. We evaluate how age of onset could guide referral for genetic testing. Methods: We analyzed the age distribution of RCC cases in the Surveillance and Epidemiology and End Results (SEER-17) program and from our institutional hereditary kidney cancer population. The age distributions were compared by sex, race, histology, and hereditary syndrome. Models were established to evaluate the specific age thresholds for genetic counseling. Results: The median age of RCC in SEER-17 was 64 years old with the distribution closely approaching normalcy. Statistical differences were observed by race, sex, and subtype (p < 0.05). The bottom decile overall was 46 years of age and slightly differed by sex, race, and histology. The mean and median age of 608 cases of hereditary kidney cancer was 39.3 and 37 years old. While age varied by specific syndrome, 70% of the hereditary cases lied below the bottom age decile. Modeling demonstrated that age alone could limit the number of patients for counseling and that the 10^th percentile maximized sensitivity and specificity. Conclusions: Besides associated clinical manifestations and personal/family history, early age of onset in RCC could be a sign of a hereditary kidney cancer. In the absence of clinical signs, an age of onset ≤46 should trigger referral for genetic counseling and may serve as a useful cutoff when establishing genetic testing guidelines.

315 Background: Micropapillary Urothelial Bladder Carcinoma (MPBC) is a rare aggressive variant histology of bladder cancer. Management of non-muscle invasive (NMI) MPBC is controversial, as bladder sparing strategies routinely used when managing TCC have resulted in worse outcomes. In order to better understand its behavior, we reviewed all MPBC pts in the SEER database and compared them with TCC pts. Methods: Data was collected from SEER 17. Age, sex, race, grade, stage, treatment, and cause of death were collected. Kaplan-Meier (KM) and Cox proportional hazards (CPH) models were performed. Results: From 2001-2008, 120 pts with MPBC were identified, 0.1% of all bladder cancer. Mean age was 70.3 yrs, 76.7% were male, and 90.8% were Caucasian. No difference in age, sex, or race was detected between MPBC and TCC pts. MPBC presented with more high grade (HG) disease (86.1% vs. 38.7%, p

307 Background: Bladder paragangliomas (BP, also referred to as bladder pheochromocytomas) represent 0.06% of bladder tumors. They occur both sporadically and with familial cancer syndromes such as von Hippel-Lindau (VHL) or Succinate Dehydrogenase-B (SDH-B) deficiency. Here we describe the clinical manifestations and management of BP at our institution. Methods: A retrospective review was performed of all cases of BP treated by the Urologic Oncology Branch at the National Institutes of Health (NIH) Clinical Center from 1989 – 2012. Using an approved database, we reviewed the demographics, radiologic, pathologic, laboratory data, surgical approach, and clinical outcome of patients with BP. Results: A total of 7 patients were treated for BP. Five were part of familial syndromes (3 with VHL, 2 with SDH-B deficiency, mean tumor volume (TV): 4cc), while 2 were sporadic cases (mean TV: 43cc). There was no significant age or gender difference in sporadic versus familial patients. 6 of the 7 patients presented with at least two of the three classic symptoms of headache, palpitations, and diaphoresis. 3 patients had micturition-related symptoms. For diagnosis, urine and plasma normetanephrines and urine norephinephrine showed the greatest sensitivity (0.75, 0.75, and 0.8, respectively). MRI was performed in all patients and had a sensitivity of 100% for detection of the mass. MIBG scan was also 100% sensitive, but was only performed in 3 of the 7 patients. CT missed the lesion in one patient. 3 patients were treated with TURBT (mean TV: 2.2cc), 2 underwent partial cystectomies (mean TV: 11.6cc), and one had a radical cystectomy (TV: 63cc). 2 patients had metastatic disease detected 7 and 9 years after initial treatment. No difference was seen in outcome based on the treatment modality. Conclusions: BP in familial and sporadic cases present with similar characteristics except for size. BP is best detected with catecholamines and MIBG/MRI. Surgical management is largely dictated by the extent of disease and includes TURBT, partial, and radical cystectomy. Long-term monitoring is recommended as distant recurrences can occur.

Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Sarcomatoid renal cell carcinoma can occur in the setting of all histological subtypes of kidney cancer. These tumours are very aggressive and many patients present with disseminated disease. Long‐term survival is poor and the durable responses to systemic therapy are infrequent. Our large cohort analyses the influence of pathological tumour characteristics in determining prognosis for patients with sarcomatoid renal cell carcinoma undergoing surgical resection. This series helps define the prognostic influence of histological subtype, type of sarcomatoid morphology, the percentage necrosis and sarcomatoid features, and the presence of microvascular invasion. OBJECTIVES: To examine the influence of pathological tumour characteristics on survival to aid prognostication and clinical trial design. Patients with sarcomatoid renal cell carcinoma (sRCC) are known to have poor prognosis and response to systemic therapy. PATIENTS AND METHODS: A single‐centre database was reviewed to identify all patients with sRCC. Clinical variables and pathological information, including histology, necrosis, percentage of sarcomatoid features (PSF) and microvascular invasion (MVI), were recorded and correlated to outcome. RESULTS: Analyses of 104 patients with sRCC found that the median (range) size of tumours was 9.5 cm (2.5–30), 65% of patients had areas of clear cell histology, and 69.2% had metastatic disease at presentation. The PSF did not influence tumour size, stage, necrosis, MVI, nodes or metastasis. A total of 85 patients (81.7%) died during the follow‐up period with a median (95% confidence interval [CI]) survival of 5.9 months (4.7–8.9). In the overall cohort, Eastern Cooperative Group performance status (ECOGPS), tumour size and metastatic disease were independent predictors of poor survival. MVI, PSF and percentage necrosis were strongly associated with outcome but were not independent predictors of outcome. A multivariate risk model was established that incorporated six covariates (tumour size, MVI, ECOGPS, PSF, necrosis, and metastatic disease) to produce a predictive tool. CONCLUSIONS: Both patients with localized and metastatic sRCC have very poor survival outcomes. Pathological features MVI, PSF and necrosis are important predictors of survival and could be used in a prognostic model while grade and histology do not influence prognosis. A prognostic model, if validated, could aid in patient counselling and/or clinical trial design.