Alice Crane

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.

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

OBJECTIVE To examine the association between absence of disease on confirmatory biopsy and risk of pathologic reclassification in men on active surveillance (AS). MATERIALS AND METHODS Men 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. RESULTS Out 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%; P = .01) and volume reclassification (66.3% vs 87.4%; P = .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; P = .03) and volume reclassification (hazard ratio, 0.32; 95% confidence interval, 0.17-0.61; P = .0006) at a median of 4.7 years. CONCLUSION Absence 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.

Penile-sparing modalities in the management of low-stage penile cancer

Penile-sparing modalities are gaining widespread adoption for the management of low-stage penile cancer due to an increasing demonstration of sound oncologic, cosmetic, sexual, psychosocial, and quality of life outcomes. This review aims to provide a comprehensive overview of the respective treatment options in the armamentarium of the practicing urologist in dealing with this rare but problematic condition.

Urinary Diversion in Renal Transplantation

Renal transplantation involving anatomically or functionally altered recipient urinary reservoirs is a challenging procedure. Initial reports discouraged kidney transplantation in patients with urinary diversion due to inferior outcomes. However, more recent studies have shown that although there are more infectious complications, patients with urinary diversions have comparable long-term graft survival with those with native anatomy. Careful preoperative assessment of these candidates is mandatory. Unique technical and surgical concepts must be considered before embarking on transplanting this specific cohort of kidney transplantation candidates.

Simultaneous versus Pretransplant Native Nephrectomy in Autosomal Dominant Polycystic Kidney Disease Patients

Introduction 50% of autosomal dominant polycystic kidney disease (ADPKD) patients will develop ESRD. For those patients who undergo renal transplantation (RT) and require a native nephrectomy (NN), the optimal timing of NN in relation to RT remains unknown. Materials and Methods We retrospectively reviewed 216 adult patients who underwent RT for ADPKD from 2005 to 2017. Patients were stratified by timing of NN into 2 groups. Group 1 included patients who had simultaneous NN and RT (n=102) & Group 2 underwent NN prior to RT (n=26). Patients with post-transplant NN (n=5) and those not requiring NN (n=83) were excluded, leaving 128 patients for analysis. Data were analyzed with chi-squared or Mann-Whitney U test. Results The median age for both groups was 52 (p=0.943) and 55% were male (p=0.095). Regarding co-morbidities, 8/128 (6%) had DM at the time of transplant and 119/128 (93%) had HTN (p=0.696, 0.116, respectively). 36% of patients were symptomatic. The most common symptom was pain (25/46). Non-symptomatic patients underwent NN when the native kidney extended into the pelvis. Group 1 patients were more likely to be preemptive (47% vs. 0% [p<0.0001]) and receive living donors (58% vs 29% [p=0.007]). Median EBL for Group 1 was 500 ml (IQR 300-900) vs 200 (IQR 150-388) for Group 2 (p<0.0001). Median operative time for transplant was 458 min (IQR 351-565) for Group 1 vs. 363 min (IQR 289-410) for Group 2 (p=0.034). There were no differences in intraoperative complications (total rate 5.5%, p=0.169) or in postoperative complications (20%, p=0.094). The most frequent post-op complication was ileus (28%). Median length of stay was 6 days for both groups (p=0.268) and there was no difference in the readmission rate (p=0.81). The most frequent reason for readmission overall was infection (22%). Median creatinine (Cr) at discharge was 1.7 (IQR 1.2-3.1) for Group 1 vs 2.5 (IQR 1.6-4.6) for Group 2 (p=0.027). Creat one year was 1.6 (IQR 1.3-2.1) for Group 1 vs 1.4 (IQR 1.2-1.8) for Group 2 (p=0.110) for patients transplanted prior to 11/2016. Conclusions Patients who underwent simultaneous NN and KT experienced lower immediate post-op Cr which can likely be explained by the increased rate of living donor transplantation in this group. However, the difference in Cr disappeared within 1 year and there were no differences in perioperative complications. Our results indicate that simultaneous surgery is safe despite longer operative times and greater blood loss and that the two approaches have similar 1-year short-term outcomes. Timing decisions should be based on individual patient circumstances and patient & surgeon preference.

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.

Current Therapeutic Strategies in Clinical Urology

The field of urology encompasses all benign and malignant disorders of the urinary tract and the male genital tract. Urological disorders convey a huge economic and patient quality-of-life burden. Hospital acquired urinary tract infections, in particular, are under scrutiny as a measure of hospital quality. Given the prevalence of these pathologies, there is much progress still to be made in available therapeutic options in order to minimize side effects and provide effective care. Current drug delivery mechanisms in urological malignancy and the benign urological conditions of overactive bladder (OAB), interstitial cystitis/bladder pain syndrome (IC/BPS), and urinary tract infection (UTI) will be reviewed herein. Both systemic and local therapies will be discussed including sustained release formulations, nanocarriers, hydrogels and other reservoir systems, as well as gene and immunotherapy. The primary focus of this review is on agents which have passed the preclinical stages of development.

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.

MP15-15 A RETROSPECTIVE REVIEW OF A LARGE ACTIVE SURVEILLANCE COHORT IN PATIENTS WITH PROSTATE CANCER AT THE CLEVELAND CLINIC

Gleason score undergrading. We compared biochemical recurrence rates (BCR) after radical prostatectomy between patients with active surveillance (AS) suitable prostate cancer versus wider defined low risk prostate cancer and the effect of Gleason score upgrading after surgery. METHODS: Two prostatectomy cohorts were combined. Lowrisk PC was defined as T1-2, Gleason 6 prostate cancer and AS-suitable prostate cancer was defined using the ‘PRIAS-criteria’ as T1-2, PSA 1⁄4<10 ng/ml, PSA density <0.2 ng/ml/ml, 1-2 positive biopsies, Gleason 3+31⁄46. Kaplan-Meier curves of patients with and without Gleason score upgrading were compared using the Log-Rank test. We hypothesized that perfect pre-operative biopsy Gleason grading would lead to 0% upgrading after surgery. RESULTS: We included 755 patients of whom 181 (24%) suitable for AS, 324 (44%) had Gleason upgrading after surgery (to 6.5 in non-AS suitable versus 6.3; p1⁄40.005), and 132 (18%) showed BCR a median of 1.0 year after prostatectomy. For the total group, the 5-year BCR rate was 27%. Regarding the entire low risk group of T1-2 Gleason 6 prostate cancer, Gleason upgrading at surgery was significantly associated with unfavorable BCR rates (Figure 1a; p<0.01). Within the selected group of more favorable risk disease suitable for AS, Gleason upgrading at surgery was not associated with BCR rates (Figure 1b; p1⁄40.936). In patients who did not have Gleason upgrading, patients who were not suitable for AS showed similar BCR rates to patients who did fulfill all AS criteria (Figure 1c; p1⁄40.155). A limitation is the retrospective design; prospective validation is needed. CONCLUSIONS: In the selected group of favorable risk patients considered suitable for AS, no unfavorable effect on BCR rates was found of Gleason undergrading. This may question the additional value of reducing biopsy undergrading with new imaging techniques. In patients not fulfilling the strict AS criteria, exclusion of Gleason upgrading resulted however in BCR rates similarly favorable to patients who were suitable for AS. This may suggest that MRI could be used to expand selection criteria for AS if Gleason upgrading could be excluded.