Michael Gong

The Effect of Sunitinib on Primary Renal Cell Carcinoma and Facilitation of Subsequent Surgery

PURPOSEnWe investigated the effect of sunitinib on locally advanced primary renal carcinoma tumors and the ability to facilitate subsequent surgery.nnnMATERIALS AND METHODSnPatients with an unresectable primary renal tumor, with or without distant metastases, received 50 mg sunitinib with continuous daily dosing in a phase II trial. Computerized tomography was performed every 12 weeks to determine surgical resectability. The primary end point of the trial was the percentage of patients with renal cell carcinoma and initially unresectable primary tumors who could undergo nephrectomy after sunitinib therapy.nnnRESULTSnOf 30 patients enrolled in the study (19 with distant metastases) 28 (35 total renal tumors) were evaluable for response. The median change in primary renal cell carcinoma tumors was a 22% decrease, corresponding to a median absolute reduction of 1.2 cm. The median reduction in primary renal cell carcinoma tumors of clear cell histology was -28% (absolute reduction 1.7 cm) compared to a 1.4% increase (0.1 cm absolute increase) in nonclear cell tumors. Of these patients 13 (45%) met the primary end point of being able to undergo nephrectomy after preoperative sunitinib. All patients had viable renal cell carcinoma in the surgical specimen and surgical morbidity was consistent with prior experience of nephrectomy in patients without preoperative therapy.nnnCONCLUSIONSnSunitinib as initial therapy in patients with locally advanced features of the primary tumor was feasible and resulted in an antitumor effect that enabled subsequent surgery in a subset of patients. Further prospective study is required to refine the most suitable application of this approach.

Transrectal Saturation Technique May Improve Cancer Detection as an Initial Prostate Biopsy Strategy in Men with Prostate-specific Antigen <10 ng/ml

BACKGROUNDnUsing transrectal saturation prostate biopsy (SPBx) as an initial strategy remains a controversial topic.nnnOBJECTIVEnTo compare SPBx with extended prostate biopsy (EPBx) as an initial biopsy template in a large sequential cohort study.nnnDESIGN, SETTING, AND PARTICIPANTSnWe reviewed 438 men with initial SPBx and 3338 men who underwent initial EPBx between January 2002 and October 2011.nnnINTERVENTIONnOffice-based SPBx under periprostatic local anesthesia.nnnOUTCOME MEASUREMENTS AND STATISTICAL ANALYSISnThe yield of SPBx was compared with EPBx. Multivariable logistic regression models addressed cancer detection (CD) and cancer characteristics.nnnRESULTS AND LIMITATIONSnOverall CD was 51.6% and 42.6% in men who underwent initial SPBx and EPBx, respectively. Multivariate analysis confirmed that SPBx was an independent predictor factor correlated with the CD (odds ratio [OR]: 1.66; 95% confidence interval [CI], 1.30-1.92). Stratified by prostate-specific antigen (PSA) values, CD was higher in SPBx compared with EPBx, 47.1% versus 32.8% (OR: 2.00; 95% CI, 1.19-3.38) in patients with a PSA <4 ng/ml and 50.9% versus 42.9% in patients with a PSA from 4 ng/ml to 9.9 ng/ml (OR: 1.62; 95% CI, 1.20-2.20). By contrast, SPBx did not increase CD in men with a PSA >10 ng/ml (60.0% vs 61%; OR: 1.42; 95% CI, 0.70-2.89). There was no significant difference in the detection of insignificant cancer (p = 0.223) or low-risk cancer (p = 0.077) between the two biopsy schemes. The limitation of our study is its retrospective nature and inhomogeneity.nnnCONCLUSIONSnCompared with EPBx, SPBx significantly increases CD as an initial biopsy strategy in men with a PSA <10 ng/ml without a significant increase in the detection of insignificant cancer. These findings suggest that SPBx may merit further investigation as an initial biopsy strategy in men with a PSA <10 ng/ml in hopes of avoiding repeat biopsy for missed malignancy during the initial biopsy.

Surgical Salvage of Thermal Ablation Failures for Renal Cell Carcinoma

PURPOSEnCryoablation and radio frequency ablation are attractive modalities for small renal masses in patients with substantial comorbidities. However, salvage extirpative therapy for local recurrence after thermal ablation can be challenging due to associated perinephric fibrosis.nnnMATERIALS AND METHODSnPatients with thermal ablation refractory tumors requiring surgical salvage from 1997 to 2013 were identified and retrospectively reviewed.nnnRESULTSnA total of 27 patients were treated surgically after cryoablation (18) or radio frequency ablation (9) failed. Subjective assessment indicated moderate/severe fibrosis in 22 cases (81%). Partial nephrectomy was preferred in all patients but was not possible in 12, primarily due to unfavorable tumor size/location. In thexa0intended partial nephrectomy group (15) open surgery was performed in all patients and completed in 14, with the procedure aborted in 1 due to extensive perinephric fibrosis. Radical nephrectomy was planned in 12 patients, of whom 8 were treated laparoscopically with 1 requiring conversion to open. Median estimated blood loss was 225 ml. Overall 17 patients experienced no complications and 4 had minor complications. However, 6 patients experienced more significant complications (Clavien III-IVb). Since January 2008 partial nephrectomy was performed more frequently (12 of 17, or 71% vs 2 of 10, or 20% for previous cases, p=0.02).nnnCONCLUSIONSnSurgical salvage after failed thermal ablation is feasible in most instances, and partial nephrectomy is often possible but can be challenging due to associated perinephric fibrosis. The difficulty of surgical salvage should be recognized as a potential limitation of the thermal ablation treatment strategy. Prospective studies of thermal ablation vs partial nephrectomy should be prioritized to provide higher quality data about the merits and limitations of each approach.

Intermediate-Term Outcomes for Men with Very Low/Low and Intermediate/High Risk Prostate Cancer Managed by Active Surveillance

Purpose: We compare intermediate term clinical outcomes among men with favorable risk and intermediate/high risk prostate cancer managed by active surveillance. Materials and Methods: A total of 635 men with localized prostate cancer have been on active surveillance since 2002 at a high volume academic hospital in the United States. Median followup is 50.5 months (IQR 31.1–80.3). Time to event analysis was performed for our clinical end points. Results: Of the cohort 117 men (18.4%) had intermediate/high risk disease. Overall 5 and 10‐year all cause survival was 98% and 94%, respectively. Cumulative metastasis‐free survival at 5 and 10 years was 99% and 98%, respectively. To date no cancer specific deaths had been observed. Overall freedom from intervention was 61% and 49% at 5 and 10 years, respectively. Overall cumulative freedom from failure of active surveillance, defined as metastasis or biochemical failure after local therapy with curative intent, was 97% and 91% at 5 and 10 years, respectively. Of the men 21 (9.9%) experienced biochemical failure after deferred treatment and the 5‐year progression‐free probability was 92%. Compared to men with favorable risk disease those with intermediate/high risk cancer experienced no difference in metastases, surveillance failure or curative intervention. However, patients at higher risk were at significantly increased risk for all cause mortality, likely reflecting patient selection factors. These conclusions may be limited by the small number of events and the duration of our study. Conclusions: Patients with localized prostate cancer who are on active surveillance demonstrated a low rate of active surveillance failure, prostate cancer specific mortality and metastases regardless of baseline risk.

Genomic Scores are Independent of Disease Volume in Men with Favorable Risk Prostate Cancer: Implications for Choosing Men for Active Surveillance

Purpose: We sought to determine whether disease volume at prostate biopsy would correlate with genomic scores among men with favorable risk prostate cancer. Materials and Methods: We identified all men with NCCN® (National Comprehensive Cancer Network®) very low and low risk disease who underwent Oncotype DX® prostate testing at our institution from 2013 to 2016. Disease volume was characterized as the percent of positive cores, the number of cores with greater than 50% involvement, the largest involvement of any single core and prostate specific antigen density. Nonparametric testing was performed to compare the median Genomic Prostate Score™ and the likelihood of favorable pathology findings between quartiles of disease volume. Results: We identified 112 (37.8%) and 184 men (62.2%) at NCCN very low and low risk, respectively. Median scores did not differ significantly between disease volume quartiles (all p >0.05). However, the median likelihood of favorable pathology findings statistically differed between volume quartiles (all <0.05). Seven of the 105 men (6.3%) with very low risk disease were reclassified at low risk and 13 of 181 (7.2%) with low risk disease were reclassified at intermediate risk. Genomic disease reclassification did not depend on biopsy tumor volume. Conclusions: In patients with NCCN very low and low risk prostate cancer genomic scores did not demonstrate meaningfully significant differences by volume based on clinically established cutoff points. Moreover, genomic scores identified and reclassified men with higher risk disease despite generally acceptable surveillance characteristics in this group according to grade and volume. This suggests that in patients at low risk the tumor biological potential measured by genomics rather than by volume should inform decisions on active surveillance candidacy.

The use of bovine pericardium for complex urologic venous reconstruction.

OBJECTIVEnTo describe the use of bovine pericardium (BP) in several scenarios for venous patching and as a tubularized graft in urologic surgery.nnnMETHODSnBP was used as patch or tubularized graft in 7 patients between 2010 and 2013. Clinical scenarios and operative indications were reviewed. We used BP as a patch graft for the inferior vena cava (IVC) (N = 3) and for the iliac venous system (N = 1) to restore venous outflow. Tubularized grafts were used (N = 2) to replace the left renal vein in oncology procedures and during renal autotransplantation (N = 1). Surgical technique is reviewed in detail.nnnRESULTSnWe used BP as a venous patching in 4 cases and as a tubularized graft in 3 cases. There was no evidence of venous thrombosis of the replaced system with a mean of 14.8 months (range, 9-26) follow-up.nnnCONCLUSIONnThe use of BP as a patch or tubularized graft is an option for complicated urologic venous reconstruction. Although the follow-up interval is relatively short and this initial series small, our initial results are promising.

Prognostic Factors and Risk Stratification in Invasive Upper Tract Urothelial Carcinoma

Micro‐Abstract Upper tract urothelial carcinoma is a rare disease and most of the treatment guidelines are extrapolated from urothelial carcinoma of the bladder. In this retrospective study, we were able to identify baseline features, treatment patterns, and prognostic factors, which could be used in risk stratification, management decision‐making, and disease‐specific clinical trial design. Background: Upper tract urothelial carcinoma (UTUC) accounts for approximately 5% of all urothelial cancers. Because of similarities in morphology and histology between UTUC and urothelial carcinoma of the bladder, most treatment guidelines used for UTUC are extrapolated from the urothelial bladder carcinoma setting. With the emergence of new treatment modalities, such as immunotherapy, UTUC‐specific prognostic and predictive models are needed. Patients and Methods: A retrospective study of 454 UTUC patients who received surgery at Cleveland Clinic (1995‐2014) was conducted. Univariable and multivariable analysis (MVA) was used to identify independent predictors of progression‐free survival (PFS) and overall survival (OS). Results: Two hundred eighty‐six patients with invasive UTUC were identified with pT1, pT2, pT3, and pT4 in 93 (33%), 51 (18%), 126 (44%), and 16 (6%), respectively. Most patients (76%) had laparoscopic nephroureterectomy, 14% had positive invasive surgical margins, and 22% had multifocal tumors. All patients had urothelial carcinoma as primary histology, 93 of 183 (51%) with available follow‐up data had disease recurrence. Estimated median PFS was 17.2 months (95% confidence interval [CI], 13.1‐39.3). In MVA, pT stage (P = .0005), positive margins (P = .04), and age older than 70 years (P = .002) independently correlated with PFS. Overall, 101 patients (37%) of 272 patients with available data died with estimated median OS of 64.5 months (95% CI, 39.3‐107.4); median follow‐up was 39.5 (range, 0.3‐186) months in patients alive and recurrence‐free at last follow‐up. In MVA, lymphovascular invasion (P = .005), tumor size (P = .0005), age (P = .005), and pT stage (P = .03) independently predicted OS. Using these factors, 3 prognostic groups for PFS and 2 for OS were identified. Conclusion: Clinical‐pathological parameters can be prognostic in UTUC and might inform clinical trial design and decision‐making.

Prognostic Significance of a Negative Confirmatory Biopsy on Reclassification Among Men on Active Surveillance

OBJECTIVEnTo examine the association between absence of disease on confirmatory biopsy and risk of pathologic reclassification in men on active surveillance (AS).nnnMATERIALS AND METHODSnMen with grade groups 1 and 2 disease on AS between 2002 and 2015 were identified who received a confirmatory biopsy within 1 year of diagnosis and ≥3 biopsies overall. The primary outcomes were pathologic reclassification by grade (any increase in primary Gleason pattern or Gleason score) or volume (>33% of sampled cores involved or increase in the number of cores with >50% involvement). The effect of a negative confirmatory biopsy survival was evaluated using Kaplan-Meier analysis and a Cox proportional hazards modeling.nnnRESULTSnOut of 635 men, 224 met inclusion criteria (median follow-up: 55.8 months). A total of 111 men (49.6%) had a negative confirmatory biopsy. Decreased grade reclassification (69.7% vs 83.9%; Pu2009=u2009.01) and volume reclassification (66.3% vs 87.4%; Pu2009=u2009.004) was seen at 5 years for men with a negative confirmatory biopsy compared with those with a positive biopsy. On adjusted analysis, a negative confirmatory biopsy was associated with a decreased risk of grade reclassification (hazard ratio, 0.51; 95% confidence interval, 0.28-0.94; Pu2009=u2009.03) and volume reclassification (hazard ratio, 0.32; 95% confidence interval, 0.17-0.61; Pu2009=u2009.0006) at a median of 4.7 years.nnnCONCLUSIONnAbsence of cancer on the confirmatory biopsy is associated with a significant decrease in rate of grade and volume reclassification among men on AS. This information may be used to better counsel men on AS.

Impact of 5α-Reductase Inhibitors on Disease Reclassification among Men on Active Surveillance for Localized Prostate Cancer with Favorable Features

Purpose: We determined the effect of 5&agr;‐reductase inhibitors on disease reclassification in men with prostate cancer optimally selected for active surveillance. Materials and Methods: In this retrospective review we identified 635 patients on active surveillance between 2002 and 2015. Patients with favorable cancer features on repeat biopsy, defined as absent Gleason upgrading, were included in the cohort. Patients were stratified by those who did or did not receive finasteride or dutasteride within 1 year of diagnosis. The primary end point was grade reclassification, defined as any increase in Gleason score or predominant Gleason pattern on subsequent biopsy. This was assessed by multivariable Cox proportional hazards regression analysis. Results: At diagnosis 371 patients met study inclusion criteria, of whom 70 (19%) were started on 5&agr;‐reductase inhibitors within 12 months. Median time on active surveillance was 53 vs 35 months in men on vs not on 5&agr;‐reductase inhibitors (p <0.01). Men on 5&agr;‐reductase inhibitors received them for a median of 23 months (IQR 6–37). On actuarial analysis there was no significant difference in grade reclassification for 5&agr;‐reductase inhibitor use in patients overall or in the very low/low risk subset. The overall percent of patients who experienced grade reclassification was similar at 13% vs 14% (p = 0.75). After adjusting for baseline clinicopathological features 5&agr;‐reductase inhibitors were not significantly associated with grade reclassification (HR 0.80, 95% CI 0.31–1.80, p = 0.62). Furthermore, no difference in adverse features on radical prostatectomy specimens was observed in treated patients (p = 0.36). Conclusions: Among our cohort of men on active surveillance 5&agr;‐reductase inhibitor use was not associated with a significant difference in grade reclassification with time.

PD55-12 OLDER AGE AT DIAGNOSIS AND DISEASE VOLUME PREDICT UPGRADING ON CONFIRMATORY BIOPSY IN PROSTATE CANCER PATIENTS BEING CONSIDERED FOR ACTIVE SURVEILLANCE

RESULTS: 3669 patients underwent RP between 1/1/04 and 12/31/15. Of these, 1454, 251 and 1361 patients fulfilled criteria for very low/low, favorable intermediate, and unfavorable intermediate-risk groups, respectively. Median follow-up was 37 months. Patients in the favorable intermediate group had significantly higher rates of Gleason score upgrading (16% vs 6%; p<0.001) and non organ-confined disease (16% vs 11%; p1⁄40.035) than those in low risk group. Time to biochemical recurrence for the favorable intermediate group did not differ significantly from the low risk group (p1⁄40.057), but was significantly longer than unfavorable intermediates (p1⁄40.003) (Figure 1). CONCLUSIONS: Compared to very low/low risk prostate cancer patients, men with favorable intermediate-risk disease had significantly higher rates of more aggressive, non-organ confined disease at RP, and trended toward worse biochemical progression free survival. However, when compared to unfavorable intermediate risk patients, it appears the magnitude of these differences would not preclude AS as a reasonable option for appropriately selected patients with favorable intermediate risk prostate cancer.