Daniel M. Halpern

Predictors of biochemical recurrence after primary focal cryosurgery (hemiablation) for localized prostate cancer: A multi-institutional analytic comparison of Phoenix and Stuttgart criteria

BACKGROUND The Phoenix definition (PD) and Stuttgart definition (SD) designed to determine biochemical recurrence (BCR) in patients with postradiotherapy and high-intensity focused ultrasound organ-confined prostate cancer are being applied to follow patients after cryosurgery. We sought to identify predictors of BCR using the PD and SD criteria in patients who underwent primary focal cryosurgery (PFC). MATERIALS AND METHODS We performed a retrospective review of patients who underwent PFC (hemiablation) at 2 referral centers from 2000 to 2014. Patients were followed up with serial prostate-specific antigen (PSA). PSA levels, pre- and post-PFC biopsy, Gleason scores, number of positive cores, and BCR (PD = [PSA nadir+2ng/ml]; SD = [PSA nadir+1.2ng/ml]) were recorded. Patients who experienced BCR were biopsied, monitored carefully or treated at the discretion of the treating urologist. Cox regression and survival analyses were performed to assess time to BCR using PD and SD. RESULTS A total of 163 patients were included with a median follow-up of 36.6 (interquartile range: 18.9-56.4) months. In all, 64 (39.5%) and 98 (60.5%) experienced BCR based on PD and SD, respectively. On multivariable Cox regression, the number of positive pre-PFC biopsy cores was an independent predictor of both PD (hazard ratio [HR] = 1.4, P = 0.001) and SD (HR = 1.3, P = 0.006) BCRs. Post-PFC PSA nadir was an independent predictor of BCR using the PD (HR = 2.2, P = 0.024) but not SD (HR = 1.4, P = 0.181). Survival analysis demonstrated a 3-year BCR-free survival rate of 56% and 36% for PD and SD, respectively. Of those biopsied after BCR, 14/26 (53.8%) using the PD and 18/35 (51.4%) using the SD were found to have residual/recurrent cancer. Of those with prostate cancer on post-PFC biopsy, 57.1% of those with BCR by the PD and 66.7% of those with BCR by the SD were found to have a Gleason score ≥7. CONCLUSION Both the PD and the SD may be used to determine BCR in post-PFC patients. However, the ideal definition of BCR after PFC remains to be elucidated.

Effects of Focal Versus Total Cryotherapy and Minimum Tumor Temperature on Patient-Reported Quality of Life as Compared to Active Surveillance in Prostate Cancer Patients

OBJECTIVE To investigate the effects of focal (hemiablation) or total cryotherapy and minimum tumor temperature on patient-reported quality of life (QoL) in patients with prostate cancer. METHODS An Institutional Review Board-approved database was reviewed for patients who underwent cryotherapy or active surveillance (AS). QoL questionnaire responses were collected and scores were analyzed for differences between focal and total cryotherapy and between very cold (<-76°C) and moderate-cold (≥-76°C) minimum tumor temperatures. RESULTS A total of 197 patients responded to a total of 547 questionnaires. Focal and total cryotherapy patients had initially lower sexual function scores relative to AS (year 1 mean difference focal: -31.7, P <.001; total: -48.1, P <.001). Focal cryotherapy was associated with a more rapid improvement in sexual function. Both focal and total cryotherapy sexual function scores were not statistically significantly different from the AS cohort by postprocedural year 4. Very cold and moderate-cold temperatures led to initially lower sexual function scores relative to AS (year 1 very cold: -38.1, P <.001; moderate-cold: -30.7, P <.001). Moderate-cold temperature scores improved more rapidly than those of very cold temperature. Neither very cold nor moderate-cold temperatures had a statistically significant difference in sexual function scores relative to AS by postprocedural year 4. Urinary function and bowel habits were not significantly different between focal and total cryotherapy and between very cold and moderate-cold temperature groups. CONCLUSION Focal cryotherapy and moderate-cold (≥-76°C) temperature were associated with favorable sexual function relative to total cryotherapy and very cold temperature, respectively. No significant differences in urinary function or bowel habits were observed between groups.

Patient-reported quality of life progression in men with prostate cancer following primary cryotherapy, cyberknife, or active holistic surveillance

BackgroundTechnological advancements have led to the success of minimally invasive treatment modalities for prostate cancer such as CyberKnife and Cryotherapy. Here, we investigate patient-reported urinary function, bowel habits, and sexual function in patients following CyberKnife (CK) or Cryotherapy treatment, and compare them with active holistic surveillance (AHS) patients.MethodsAn IRB-approved institutional database was retrospectively reviewed for patients who underwent CK, Cryotherapy, or AHS. Quality of life (QoL) survey responses were collected every three months and the mean function scores were analyzed in yearly intervals over the 4 years post-treatment.Results279 patients (767 survey sets) were included in the study. There was no difference among groups in urinary function scores. The CyberKnife group had significantly lower bowel habit scores in the early years following treatment (year 2 mean difference: −5.4, P < 0.01) but returned to AHS level scores by year 4. Cryotherapy patients exhibited initially lower, but not statistically significant, bowel function scores, which then improved and approached those of AHS. Both CyberKnife (year 1 mean difference: −26.7, P < 0.001) and Cryotherapy groups (−35.4, P < 0.001) had early lower sexual function scores relative to AHS, but then gradually improved and were not significantly different from AHS by the third year post-treatment. A history of hormonal therapy was associated with a lower sexual function scores relative to those patients who did not receive hormones in both CyberKnife (−18.45, P < 0.01) and Cryotherapy patients (−14.6, P < 0.05).ConclusionsAfter initial lower bowel habits and sexual function scores, CyberKnife or Cryotherapy-treated patients had no significant difference in QoL relative to AHS patients. These results highlight the benefit of CyberKnife and Cryotherapy in the management of organ-confined prostate cancer.

PD36-09 INSTITUTIONAL VOLUME IS ASSOCIATED WITH REDUCED 90 DAY MORTALITY RATES FOR BOTH OPEN AND ROBOTIC RADICAL CYSTECTOMY

The association between PBT and oncological outcomes, as well as OCM was assessed using Cox and logistic regression analyses. Imbalances in clinicopathological features of patients receiving PBT vs. patients not receiving PBT were mitigated using conventional adjusting as well as inverse probability of treatment weighting (IPTW). RESULTS: The final population consisted of 525 patients with a median follow-up of 26 months (IQR: 21-30 months) of whom 275 patients (52.4%) received PBT. The two groups (PBT vs. no PBT) differed significantly with respect to most clinicopathological features including perioperative blood loss (median: 1000ml; IQR: 650-1600ml vs. median: 570ml; IQR: 400-800ml). Independent predictors of receipt of PBT in multivariate logistic regression analysis were sex (odds ratio (OR)1⁄44.66; 95% confidence interval (CI)1⁄4[2.34-9.29]; p<0.001), body mass index (OR1⁄40.92; 95% CI1⁄4[0.87-0.97]; p1⁄40.003), type of urinary diversion (OR1⁄40.40; 95% CI1⁄4[0.22-0.75]; p1⁄40.004), estimated blood loss (OR1⁄41.29; 95% CI1⁄4 [1.21-1.39]; p<0.001), and any complication within 30 days (OR1⁄43.00; 95% CI1⁄4[1.75-5.15]; p<0.001). Unweighted and unadjusted survival analyses revealed a significant increase in cumulative incidences of CSM and OCM in the two groups (p1⁄40.017 and p<0.001, respectively). After IPTW-adjustment, those differences no longer held true. PBT was not associated with RFS (HR1⁄40.92; 95% CI1⁄4[0.53-1.59]; p1⁄40.76), OS (HR1⁄41.07; 95% CI1⁄4[0.56-2.04]; p1⁄40.84), CSM (sub-HR1⁄41.09; 95% CI1⁄4[0.62-1.93]; p1⁄40.76) and OCM (sub-HR1⁄41.02; 95% CI1⁄4[0.27-3.84]; p1⁄40.95) in IPTW-adjusted Cox regression and competing-risks regression analyses. The same held true in conventional multivariate Cox and competing-risks regression analyses, where pathological tumor stage and lymphovascular invasion were the only independent predictors of CSM (HR1⁄43.71, 95% CI1⁄4[2.06-6.68], p<0.001 and HR1⁄42.49, 95% CI1⁄4 [1.43-4.33], p<0.001) aswell as disease recurrence (HR1⁄44.48, 95%CI1⁄4 [2.45-8.16], p<0.001 and HR1⁄42.76, 95% CI1⁄4[1.56-4.87], p<0.001). CONCLUSIONS: This study could not determine an adverse impact of PBT on oncological outcome and overall survival after adjusting for differences in patient characteristics.

MP70-04 3-T MULTIPARAMETRIC MRI CHARACTERISTICS OF PROSTATE CANCER PATIENTS SUSPICIOUS FOR BIOCHEMICAL RECURRENCE AFTER PRIMARY FOCAL CRYOSURGERY.

Source of Funding: This research was made possible through the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH by the Doris Duke Charitable Foundation (Grant #2014194), the American Association for Dental Research, the Colgate-Palmolive Company, Genentech, and other private donors. For a complete list, visit the foundation website at http://www.fnih. org.

PD56-09 PSA TRENDS FOLLOWING PRIMARY FOCAL CRYOSURGERY FOR EARLY STAGE PROSTATE CANCER

METHODS: Participants were eligible when diagnosed with intermediate risk, unilateral clinically significant localised prostate cancer, fit for either RP or PA. Pre-biopsy mpMRI and targeted biopsy or template guided biopsies were compulsory before randomization to either RP or PA. Target accrual for the feasibility phase was 80 patients over 18 months. Follow-up involved regular PSA measurements and, in the focal therapy arm, mpMRI and targeted biopsies of any suspicious areas. Quality of life data were measured at six weeks and three monthly intervals. RESULTS: The table below summarises recruitment data. Baseline demographics of men randomised to date are Mean age: 66.7yrs (48.4-78.2); BMI: 26.4 (22.0-32.3); PSA: 7.60 (2.5-16.20) and Gleason score: 3+41⁄47 75.6%, 4+31⁄47 24.4%. CONCLUSIONS: A randomised controlled trial of partial ablation of the prostate versus radical treatment with surgery is feasible. The full trial is being developed, and will provide key data to inform men when making the treatment decision for intermediate risk unilateral prostate cancer.

MP70-09 PREDICTORS OF BIOCHEMICAL RECURRENCE AFTER PRIMARY FOCAL CRYOTHERAPY FOR LOCALIZED PROSTATE CANCER: A MULTI-INSTITUTIONAL ANALYTIC COMPARISON OF THE PHOENIX AND STUTTGART CRITERIA

INTRODUCTION AND OBJECTIVES: The Phoenix (PD) and Stuttgart definitions (SD) are used to define biochemical recurrence (BCR) in patients after radiotherapy and High Intensity Focused Ultrasound treatment of organ-confined prostate cancer (PCa) respectively. However, these definitions have also been applied to follow patients who have undergone cryosurgery. We sought to identify predictors of BCR using the PD and SD criteria and evaluate each criterion0s ability to predict biopsy-proven recurrence in primary focal cryosurgery (PFC) patients. METHODS: We performed a retrospective review of patients who underwent PFC at two tertiary care centers. Patients were followed with serial prostate specific antigen (PSA) tests. PSA levels, preand post-PFC biopsy Gleason scores, number of positive cores, and BCR (defined as: PD 1⁄4 [PSA nadir + 2 ng/mL] and SD 1⁄4 [PSA nadir + 1.2 ng/ mL]) were recorded. Patients who experienced BCR were biopsied, monitored carefully or treated at the discretion of the treating urologist. Cox proportional regression and survival analyses were performed to assess time to BCR using the PD and SD criteria. RESULTS: Of 162 patients included [median (range) follow up: 36.6 (2.8-109.4) months] in the study, 64 (39.5%) and 98 (60.5%) experienced BCR based on PD and SD, respectively. On multivariate Cox regression analysis, the number of positive pre-PFC biopsy cores was an independent predictor of both PD (Hazard Ratio [HR]: 1.4, p1⁄40.001) and SD (HR: 1.3, p1⁄40.006) BCRs. Post-PFC PSA nadir was an independent predictor of BCR using the PD (HR: 2.2, p1⁄40.024) but not SD (HR: 1.4, p1⁄40.181) BCR. Survival analysis showed a 3-year BCR free survival of 55% and 36% for PD and SD respectively. Of those biopsied after BCR, 14/26 (53.8%) using the PD and 18/35 (51.4%) using the SD were found to have cancer (57.1% PD and 66.7% SD were clinically significant PCa). CONCLUSIONS: Both the PD and the SD showed about a 50% biopsy-proven rate of recurrence after PFC. The number of positive cores on pretreatment biopsy appears to be a significant predictor of failure after PFC. The ideal definition of BCR after PFC remains to be elucidated.

PD67-05 FACILITY VOLUME AND TYPE IS ASSOCIATED WITH RECEIPT OF CONTINENT DIVERSION FOR BOTH OPEN AND ROBOTIC RADICAL CYSTECTOMY

INTRODUCTION AND OBJECTIVES: Continent urinary diversion (CUD) can offer improved quality of life in select patients follow in radical cystectomy (RC). We aim to evaluate the rate of receipt of CUD in robotic assisted RC (RARC) and open RC (ORC) based on hospital volume and facility type in the National Cancer Data Base. METHODS: We divided all cystectomy cases into volume categories (defined as: 1-2.9, 3-4.9, 5-9.9, 10-19.9 and 20+ cystectomies/ year) and facility type (academic/research (AR), comprehensive community (CC) and other), type of surgery (ORC or RARC) to assess the patterns in the rate of receipt of CUD. To assess the relationship between facility characteristics and receipt of CUD, chi-square was used. Univariate and multivariable logistic regression models for CUD rates were used to adjust for patient, tumor and facility characteristics. RESULTS: 16,923 RC cases were identified (ORC 1⁄4 13,236, RARC1⁄43,687). Overall, 5.7% of ORC (754) and 7.1% of RARC (261) received CUD (p1⁄40.003). RARC had higher rates of receiving CUD compared to ORC in all volume categories except for the highest volume centers (10.2% vs 9.7%). Rates of receipt of CUD increased with increasing RC volume centers (p1⁄40.01); in the ORC group (2.8 vs. 10.2%), and in the RARC group by (5.7% vs. 9.7%; p for interaction1⁄40.10). In adjusted models, center volume remained a highly significant predictor of CUD receipt (p<0.001). Rates of receipt of CUD were higher in RARC vs. ORC in CC and other facility types, but were equal in AR facilities. The difference in the rate of CUD receipt between facility types was significant for ORC (p1⁄40.001) but not for RARC (p1⁄40.09). CUD receipt was observed to decrease linearly over time in both ORC (6.9% in 2010 vs. 4.7 in 2013; p1⁄40.001) and RARC (9.4% in 2010 vs. 6.0% in 2013; p1⁄40.06). CONCLUSIONS: Increasing facility cystectomy volume was associated with increased rates of receipt of CUD in both open and robotic cystectomy while facility type was only significant for open surgeries. The overall rate of receiving CUD was higher in RARC versus ORC surgeries but the overall rate of patients receiving continent diversions remains low and may be decreasing.

PD67-06 PATHOLOGIC METRICS OF SURGICAL QUALITY IN OPEN AND ROBOTIC RADICAL CYSTECTOMY IMPROVED AT HIGHER VOLUME AND ACADEMIC CENTERS

INTRODUCTION AND OBJECTIVES: Continent urinary diversion (CUD) can offer improved quality of life in select patients follow in radical cystectomy (RC). We aim to evaluate the rate of receipt of CUD in robotic assisted RC (RARC) and open RC (ORC) based on hospital volume and facility type in the National Cancer Data Base. METHODS: We divided all cystectomy cases into volume categories (defined as: 1-2.9, 3-4.9, 5-9.9, 10-19.9 and 20+ cystectomies/ year) and facility type (academic/research (AR), comprehensive community (CC) and other), type of surgery (ORC or RARC) to assess the patterns in the rate of receipt of CUD. To assess the relationship between facility characteristics and receipt of CUD, chi-square was used. Univariate and multivariable logistic regression models for CUD rates were used to adjust for patient, tumor and facility characteristics. RESULTS: 16,923 RC cases were identified (ORC 1⁄4 13,236, RARC1⁄43,687). Overall, 5.7% of ORC (754) and 7.1% of RARC (261) received CUD (p1⁄40.003). RARC had higher rates of receiving CUD compared to ORC in all volume categories except for the highest volume centers (10.2% vs 9.7%). Rates of receipt of CUD increased with increasing RC volume centers (p1⁄40.01); in the ORC group (2.8 vs. 10.2%), and in the RARC group by (5.7% vs. 9.7%; p for interaction1⁄40.10). In adjusted models, center volume remained a highly significant predictor of CUD receipt (p<0.001). Rates of receipt of CUD were higher in RARC vs. ORC in CC and other facility types, but were equal in AR facilities. The difference in the rate of CUD receipt between facility types was significant for ORC (p1⁄40.001) but not for RARC (p1⁄40.09). CUD receipt was observed to decrease linearly over time in both ORC (6.9% in 2010 vs. 4.7 in 2013; p1⁄40.001) and RARC (9.4% in 2010 vs. 6.0% in 2013; p1⁄40.06). CONCLUSIONS: Increasing facility cystectomy volume was associated with increased rates of receipt of CUD in both open and robotic cystectomy while facility type was only significant for open surgeries. The overall rate of receiving CUD was higher in RARC versus ORC surgeries but the overall rate of patients receiving continent diversions remains low and may be decreasing.