Citations

Objectives To compare renal functional changes after percutaneous cryoablation ( PCA ) or partial nephrectomy ( PN ). Patients and Methods Patients who underwent PCA or PN for a solitary renal mass at a single institution were identified (2003–2013). Estimated glomerular filtration rates ( eGFR s) were calculated at baseline, discharge, and at the 3‐month follow‐up using the Chronic Kidney Disease Epidemiology Collaboration equation. Changes in renal function were compared between groups using 1:1 propensity score ( PS ) matching, adjustment for PS quintile, and inverse probability weighting ( IPW ). Results There were 2 040 procedures available for the PS analyses, including 448 PCA and 1 592 PN . After PS adjustments, there were no significant differences in baseline clinical features between PCA and PN patients. In the PS ‐matched analysis, the change in eGFR from baseline to discharge for PCA and PN patients was −3.1 and −1.1 mL /min/1.73 m 2 , respectively ( P = 0.038), with percentage changes of −4.5% and 0% respectively ( P = 0.006). From baseline to the 3‐month follow‐up, the absolute change in eGFR for PCA and PN patients was −4.3 and −2.1 mL /min/1.73 m 2 , respectively ( P = 0.008), and the percentage change was −6.1% and −2.4% respectively ( P = 0.005). Similar results were obtained after adjusting for PS quintiles and in the IPW analysis. Importantly, the rate of chronic kidney disease stage progression at the 3‐month follow‐up was similar between the groups (21% vs 18%). Conclusions Our results confirm that both PCA and PN have a minor impact on renal function. While we observed a statistically greater decline in eGFR after PCA compared with PN , both approaches result in excellent preservation of renal function.

433 Background: Current guidelines suggest that percutaneous thermal ablation (PTA) can be utilized in those with significant comorbidity who are unable to tolerate surgery (radical or partial nephrectomy). However, the use of PTA in healthy patients, who are otherwise candidates for surgery, has been limited. Here, we reviewed our institutional experience in healthy patients electing to undergo PTA, specifically cryoablation. Methods: We identified patients ≤65 years undergoing percutaneous cryoablation for solitary, non-metastatic renal masses <7cm (cT1). We further limited our cohort to patients with an ASA score of 1 or 2, and in whom pre-operative eGFR was >60. Clincopathologic characteristics and recurrence patterns (local recurrence within the kidney versus metastatic disease) were evaluated. Results: Between March 2003 and December 2015, 705 patients underwent cryoablation, of whom 43 (6.1%) were deemed to be “healthy”. Median age of this cohort was 57 years (IQR 52−62), with pre-ablation eGFR of 75.6 (IQR 69.0-86.3). Seven patients (16.3%) had a prior partial nephrectomy, and 5 (11.6%) had a solitary kidney. The majority (40, 93.0%) of ablated masses were cT1a, with 3 (7.0%) being cT1b. Median tumor size was 2.0 cm. 27 masses (63.7%) were biopsy-proven renal cell carcinoma (RCC) and 6 (13.6%) were benign; histology was unknown in 10 (22.7%). Follow-up imaging was available for 37 patients. Median radiological follow-up was 22 months (IQR 9-42), during which time 2 patients developed metastatic disease and 1 developed local recurrence; all events were in patients with biopsy-proven RCC. No patients died from RCC during this time period. Conclusions: In this single institution cohort of “healthier” patients with cT1 solitary renal masses, cryoablation offered reasonable short term oncologic control. While longer follow-up data are needed to evaluate for durability, cryoablation in healthy patients, particularly those with challenging surgical anatomy, warrants further study.

Objective To evaluate the association between renal tumour complexity and outcomes in a large cohort of patients undergoing percutaneous cryoablation ( PCA ). Patients and Methods Patients with renal tumours treated with PCA were identified using our prospectively maintained ablation registry (2003–2015). Salvage procedures and inherited tumour syndromes were excluded. The associations between R.E.N.A.L. nephrometry score ( NS ) and risk of complications, renal function impairment, local failure and cancer‐specific mortality ( CSM ) were evaluated using univariate and multivariable logistic, linear and Cox regression models. Results The cohort included 618 tumours treated during 580 procedures in 565 patients. The median (interquartile range [ IQR ]) follow‐up was 34 (14.66) months. Complications (any grade) during a procedure ( n [total] = 87, 15%) were more frequent with higher NS ( NS 4–6: 10%; NS 7–9: 14%; NS 10–12: 36%; P < 0.001). Higher NS was independently associated with risk of complications (odds ratio [ OR ; per 1 point] = 1.3; 95% confidence interval [ CI ] 1.2–1.5; P < 0.001). Of all the NS components, tumour size was the most strongly associated with complication risk ( OR 3.4; 95% CI 2.2–5.2; P < 0.001). The median ( IQR ) decline in glomerular filtration rate ( GFR ) from baseline was 9% (0, 22) at last follow‐up. Each additional point in NS was associated with a 1.3% (95% CI 0.4–2.1; P = 0.005) greater GFR decline from baseline. NS was not significantly associated with local failure ( n [total] = 14, 2%; NS 4–6: 2%; NS 7–9: 3%; NS 10–12: 5%; P = 0.32) or CSM ( n [total] = 8, 2%; NS 4–6: 2%; NS 7–9: 3%; NS 10–12: 2%; P = 0.88). Conclusion In high‐complexity tumours PCA was associated with a tumour size‐driven increased risk of post‐procedural complications. Higher NS was associated with a small, clinically minor additional decline in renal function. Risks for local failure and CSM were low, regardless of tumour complexity.

249 Background: Evaluating tumor specific pathologic and genetic profiles in mCRPC stage is difficult due to the limited availability of mCRPC tissue. We describe findings from a prospective cohort study performed to obtain concomitant histopathology and genetic information in mCRPC. Methods: Patients with mCRPC initiating abiraterone acetate therapy underwent 2 serial (3 months apart) metastatic (met) site needle core biopsies (NCB1/2). Bone lesions were biopsied using 11-13G core needles and 18G core biopsy devices were used for non-osseous masses. Up to 4 cores were obtained at each biopsy with the 1st core (S1) sent for DNA sequencing, the 2nd (S2) for RNA sequencing, and the 3rd/4th (X3, X4) submitted for xenograft implantation. From each, 1-2 mm segments were separated and formalin-fixed for histopathologic examination (HPE). Results: A total of 54 patients, enrolled between June 2013 and July 2014, underwent 94 NCB (54 NCB1, 40 NCB2), rendering a total of 259 samples (94 S1; 75 S2; 59 X3 and 31 X4) of which 85 (32%) were positive (pos) for tumor by HPE. Positivity for tumor in S1, S2, X3, and X4 cores was 42%, 33%, 22%, and 19%, respectively. At least one core pos for met tumor was observed in 62% NCB1 and 52% NCB2 (overall 52/94; 56%). Met sites biopsied include bone (71), lymph nodes (18), liver (3), penile (1) and pelvic (1) soft tissues. HPE revealed met adenocarcinoma in 44/52, and poorly differentiated carcinoma in 8/52. Gleason grade applied to the met ranged from 3+4 to 5+5. 45/85 pos samples (53%) had > 50% tumor cellularity. Pos NCB in bone lesions was observed in 23/71 (32%), compared to 17/23 (73%) of non-bone sites (p=.0004). 85 S1 samples yielded DNA material, of which 66 (77%) had ≥10% tumoral DNA. 24 cases with negative HPE had ≥10% tumoral DNA; 7 cases with pos HPE had <10 tumoral DNA. In all, 76/94 (81%) NCB yielded tumor material either by HPE or DNA analysis. Conclusions: NCB of mCRPC is feasible and provides adequate tissue for pursuing HPE and sequencing studies. HPE of extracted material correlates with DNA sequencing data and provides complementary information on tumor features. Bone lesions yield significantly less tumoral material than non-osseous sites.

190 Background: It is not known if biopsy of CRPC stage metastases alters CTC results. We evaluated pre & post biopsy CTC counts in a prospective cohort undergoing pre-chemotherapy abiraterone acetate/prednisone (AA/P). Methods: CTC enumeration was performed on 7.5mL blood using the FDA cleared immunomagnetic/immunofluorescence assay (CellSearch). Time of blood draw for CTC counts pre/post biopsy was recorded for each biopsy. Biopsies were performed using 11/13 gauge core biopsy device for bone lesions and 18 gauge core needle biopsy device for soft tissue/nodal metastases. All patients (pts) underwent two serial biopsies 3 months apart. Change in CTC counts pre/post biopsy for visits 1 and 2 were evaluated using Wilcoxon signed rank test (significance at p<0.05). Differences in CTC count change (visit1) pre/post biopsy based on metastatic site (skeletal vs. non-skeletal) was compared using Wilcoxon rank-sum test. Results: Median age of the cohort was 74 years (IQR: 68-78); median PSA at V1 was 16.4 ng/ml (IQR: 6.4-87.6); at V2 was 11.5 ng/ml (IQR: 1.8-23.7). Of 59 pts undergoing biopsies 42 were in bone and 17 in nodal/soft tissue masses. At V1, pre/post biopsy CTC counts were measured on 50 and 49 pts, respectively; at V2, pre/post CTC counts were measured on 43 and 36 pts. High volume metastatic disease at V1 was observed in 67.8 % of all pts. Table lists CTC counts and time of collection pre/post biopsy for both visits. Mean change in pre/post biopsy CTC counts for skeletal sites was 0.7 (range: -12 to 64) compared to 12.1 (range: -21 to 13) for non-skeletal sites (p=0.23). Conclusions: An increase in mean CTC counts after biopsy of CRPC metastases was observed. No significant differences in change of CTC counts based on site biopsied (skeletal versus non-skeletal) was noted. Correlation with clinical outcomes is on-going. Clinical trial information: NCT# 01953640. [Table: see text]

237 Background: AA/P is an approved treatment for mCRPC but there are no known predictive markers of response or resistance. We conducted a prospective trial to evaluate if Androgen Receptor (AR) & AR-variant (ARV) expression in tissue metastases can predict resistance to AA/P. Methods: mCRPC stage patients (pts) initiating pre-chemo AA/P underwent metastatic site biopsies prior to (pre-AA/P) and after 12 weeks of treatment. Composite progression at 12 weeks, (primary endpoint) was evaluated with PSA, RECIST, bone scan and symptoms (per PCWG2). mRNA expressions of pre-AA/P ARFL, ARV3, ARV7, ARV9, ARV23, ARV45, four cell cycle division genes, Chromogranin-A (CHGA) together with PSA/testosterone levels, Gleason Score (GS) at initial diagnosis; high versus low volume disease; time from starting hormone therapy to mCRPC stage and serum CHGA levels were evaluated using a logistic regression model for predicting resistance at 12 weeks of therapy. A final multivariate model fitted only those factors thought to be clinically relevant or with an entry threshold of p ≤ 0.3 in univariate analysis. Results: Between 6/2013 & 3/2015, 82 pts were enrolled of which 52 had complete mRNA expression & disease assessment data at the12-week time point for analysis. Median age of the cohort was 72.5 yrs (IQR: 68.5-78); median pre-AA/P PSA was 18 ng/ml (IQR: 8.1- 46.6); GS distribution at initial diagnosis for GS 2-6; 7; 8-10 was 11; 14; 27 respectively. Progression was observed in 21/52 pts after 12 weeks. At the univariate level elevated pre-AA/P expression of ARV3 (p = 0.08), ARV7 (p = 0.26), ARV9 (p = 0.04), and cell division cycle gene CDC45 (p = 0.19) along with GS at diagnosis (p = 0.29) met the threshold for inclusion into multivariate analysis. Elevated expression of pre-therapy ARV9 in metastases alone was associated with progression at 12 weeks (OR: 3.9; CI 1.07 – 14.16; C-Index: 0.63). The 12-week biopsy of pts with progression had increased ARV9 mRNA expression compared to pts responding at 12 weeks (p = 0.14). Conclusions: Increased ARV9 mRNA expression in metastases is associated with early resistance to AA/P. This observation will need further validation in comparable datasets. Clinical trial information: NCT #0195364.

Objectives To describe the clinicopathological features associated with increased risk of renal fossa recurrence ( RFR ) after radical nephrectomy ( RN ) and to describe the prognostic features associated with cancer‐specific survival ( CSS ) among patients with RFR treated with primary locally directed therapy, systemically directed therapy or expectant management. Patients and Methods The records of 2 502 patients treated with RN for unilateral, sporadic, localized renal cell carcinoma ( RCC ) between 1970 and 2006 were reviewed. CSS after RFR was estimated using the Kaplan–Meier method. Associations with the development of RFR and CSS after RFR were evaluated using Cox proportional hazards regression models. Results A total of 33 (1.3%) patients developed isolated RFR ( iRFR ) and 30 (1.2%) patients developed RFR in the setting of synchronous metastases after RN (study cohort, N = 63). The median follow‐up for the series was 9.0 years after RN and 6.0 years after RFR diagnosis. On multivariable analysis, advanced pathological stage ( pT 2: hazard ratio [ HR ] 4.36, P = 0.004; pT 3/4: HR 4.39, P = 0.003) and coagulative necrosis ( HR 2.71, P = 0.006) were independently associated with increased risk of iRFR . The median time to recurrence was 1.5 years after RN among the 33 patients with iRFR , and 1.4 years among all patients. Overall, the median CSS was 2.5 years after diagnosis of iRFR , 1.3 years after RFR in the setting of synchronous metastases, and 2.2 years overall. After primary locally directed therapy (surgery, ablation or radiation), systemic therapy or expectant management, the 3‐year CSS rates among patients with iRFR were 63%, 50% and 13% ( P = 0.001) and were 64%, 50% and 28% ( P = 0.006) among all patients, respectively. On multivariable analysis, when compared with observation, locally directed therapies were associated with a significantly decreased risk of death from RCC ( HR 0.26, P < 0.001). Conclusions Renal fossa recurrence is a rare event after RN for RCC and portends a poor prognosis, even in the absence of synchronous metastases. Development of iRFR is associated with advanced stage and aggressive tumour biology. Patients who underwent primary locally directed therapy had superior CSS compared with those treated with expectant management, supporting the use of aggressive local treatment in carefully selected patients with RFR . Future research is needed to determine the optimum role and sequencing of combined therapy in patients with this rare entity.

SummaryObjectiveThe role of percutaneous adrenal biopsy in a high‐risk population for adrenal malignancy has not been fully investigated. Our aim was to describe the clinical presentation leading to the adrenal biopsy and evaluate the diagnostic performance, complications and non diagnostic rate of adrenal biopsy.DesignSingle‐centre, retrospective cohort study.Patients and MeasurementsMedical records of patients who underwent adrenal biopsy between 1994 and 2014 were reviewed. Adrenal biopsy outcome was compared to a predefined reference standard.ResultsBiopsy was performed in 418 patients [62% men, median age 69 years (range, 15–91)] on 419 adrenal lesions, median size 3·1 cm (range, 0·6–24). The main indication for adrenal mass biopsy was (349/419, 83%) suspected adrenal metastasis from a known or suspected extra‐adrenal primary source. Only 116 of 419, 28% of cases had prebiopsy biochemical testing for pheochromocytoma. Biopsy‐related complications occurred in 4% of the patients. Histology revealed a metastasis in 231 of 419 (55%), benign adrenal tissue in 137 of 419 (33%), adrenocortical carcinoma in eight of 419 (2%), other lesions in 23 of 419 (5%) including seven cases of pheochromocytoma and six cases of infectious process. Biopsy was nondiagnostic in 20 of 419 (5%). All adrenal masses with unenhanced radiodensity ≤10 HU (42/137, 31%) proved to be benign adrenal adenomas. Adrenal biopsy diagnosed malignancy with a sensitivity of 88·5%, specificity of 91·5%, positive predictive value of 93·4% and negative predictive value of 85·5%.ConclusionWhen used in the appropriate clinical setting, adrenal biopsy is a powerful tool in the diagnostic algorithm of the evaluation of adrenal masses with features suspicious for malignancy. Efforts to increase awareness to perform biochemical testing for pheochromocytoma prior to adrenal biopsy are needed.