Shree Agrawal

Contemporary Update of a Multi-Institutional Predictive Nomogram for Salvage Radiotherapy After Radical Prostatectomy

PURPOSE We aimed to update a previously published, multi-institutional nomogram of outcomes for salvage radiotherapy (SRT) following radical prostatectomy (RP) for prostate cancer, including patients treated in the contemporary era. METHODS Individual data from node-negative patients with a detectable post-RP prostate-specific antigen (PSA) treated with SRT with or without concurrent androgen-deprivation therapy (ADT) were obtained from 10 academic institutions. Freedom from biochemical failure (FFBF) and distant metastases (DM) rates were estimated, and predictive nomograms were generated. RESULTS Overall, 2,460 patients with a median follow-up of 5 years were included; 599 patients (24%) had a Gleason score (GS) ≤ 6, 1,387 (56%) had a GS of 7, 244 (10%) had a GS of 8, and 230 (9%) had a GS of 9 to 10. There were 1,370 patients (56%) with extraprostatic extension (EPE), 452 (18%) with seminal vesicle invasion (SVI), 1,434 (58%) with positive surgical margins, and 390 (16%) who received ADT (median, 6 months). The median pre-SRT PSA was 0.5 ng/mL (interquartile range, 0.3 to 1.1). The 5-yr FFBF rate was 56% overall, 71% for those with a pre-SRT PSA level of 0.01 to 0.2 ng/mL (n = 441), 63% for those with a PSA of 0.21 to 0.50 ng/mL (n = 822), 54% for those with a PSA of 0.51 to 1.0 ng/mL (n = 533), 43% for those with a PSA of 1.01 to 2.0 ng/mL (n = 341), and 37% for those with a PSA > 2.0 ng/mL (n = 323); P < .001. On multivariable analysis, pre-SRT PSA, GS, EPE, SVI, surgical margins, ADT use, and SRT dose were associated with FFBF. Pre-SRT PSA, GS, SVI, surgical margins, and ADT use were associated with DM, whereas EPE and SRT dose were not. The nomogram concordance indices were 0.68 (FFBF) and 0.74 (DM). CONCLUSION Early SRT at low PSA levels after RP is associated with improved FFBF and DM rates. Contemporary nomograms can estimate individual patient outcomes after SRT in the modern era.

Utilizing Low-Volume Aqueous Acoustic Transfer with the Echo 525 to Enable Miniaturization of qRT-PCR Assay.

Quantitative reverse transcription PCR (qRT-PCR) is a valuable tool for characterizing the effects of inhibitors on viral replication. The amplification of target viral genes through the use of specifically designed fluorescent probes and primers provides a reliable method for quantifying RNA. Due to reagent costs, use of these assays for compound evaluation is limited. Until recently, the inability to accurately dispense low volumes of qRT-PCR assay reagents precluded the routine use of this PCR assay for compound evaluation in drug discovery. Acoustic dispensing has become an integral part of drug discovery during the past decade; however, acoustic transfer of microliter volumes of aqueous reagents was time consuming. The Labcyte Echo 525 liquid handler was designed to enable rapid aqueous transfers. We compared the accuracy and precision of a qPCR assay using the Labcyte Echo 525 to those of the BioMek FX, a traditional liquid handler, with the goal of reducing the volume and cost of the assay. The data show that the Echo 525 provides higher accuracy and precision compared to the current process using a traditional liquid handler. Comparable data for assay volumes from 500 nL to 12 µL allowed the miniaturization of the assay, resulting in significant cost savings of drug discovery and process streamlining.

Comparison Between Adjuvant and Early-Salvage Postprostatectomy Radiotherapy for Prostate Cancer With Adverse Pathological Features

Importance Prostate cancer with adverse pathological features (ie, pT3 and/or positive margins) after prostatectomy may be managed with adjuvant radiotherapy (ART) or surveillance followed by early-salvage radiotherapy (ESRT) for biochemical recurrence. The optimal timing of postoperative radiotherapy is unclear. Objective To compare the clinical outcomes of postoperative ART and ESRT administered to patients with prostate cancer with adverse pathological features. Design, Setting, and Participants This multi-institutional, propensity score–matched cohort study involved 1566 consecutive patients who underwent postprostatectomy ART or ESRT at 10 US academic medical centers between January 1, 1987, and December 31, 2013. Propensity score 1-to-1 matching was used to account for covariates potentially associated with treatment selection. Data were collected from January 1 to September 30, 2016. Data analysis was conducted from October 1, 2016, to October 21, 2017. Main Outcomes and Measures Freedom from postirradiation biochemical failure, freedom from distant metastases, and overall survival. All outcomes were measured from date of surgery to address lead-time bias. Results Of 1566 patients, 1195 with prostate-specific antigen levels of 0.1 to 0.5 ng/mL received ESRT and 371 patients with prostate-specific antigen levels lower than 0.1 ng/mL received ART. The median age (interquartile range) was 60 (55-65) years. After propensity score matching, the median (interquartile range) follow-up after surgery was similar between the ESRT and ART groups (73.3 [44.9-106.6] months vs 65.8 [40-107] months; P = .22). Adjuvant RT, compared with ESRT, was associated with higher freedom from biochemical failure (12-year actuarial rates: 69% [95% CI, 60%-76%] vs 43% [95% CI, 35%-51%]; effect size, 26%), freedom from distant metastases (95% [95% CI, 90%-97%] vs 85% [95% CI, 76%-90%]; effect size, 10%), and overall survival (91% [95% CI, 84%-95%] vs 79% [95% CI, 69%-86%]; effect size, 12%). Adjuvant RT, lower Gleason score and T stage, nodal irradiation, and postoperative androgen deprivation therapy were favorable prognostic features on multivariate analysis for biochemical failure. Sensitivity analysis demonstrated that the decreased risk of biochemical failure associated with ART remained significant unless more than 56% of patients in the ART group were cured by surgery alone. This threshold is greater than the estimated 12-year freedom from biochemical failure rate of 33% to 52% after radical prostatectomy alone, as determined by a contemporary dynamic nomogram. Conclusions and Relevance Adjuvant RT, compared with ESRT, was associated with reduced biochemical recurrence, distant metastases, and death for high-risk patients, pending prospective validation. These findings suggest that a greater proportion of patients with prostate cancer who have adverse pathological features may benefit from postprostatectomy ART rather than surveillance followed by ESRT.

Improved surgical outcomes following radical cystectomy at high-volume centers influence overall survival

OBJECTIVES Positive surgical margins (PSM) and lymph node yield (LNY) following radical cystectomy (RC) for urothelial carcinoma of the bladder affect survival. Variations in PSM or LNY at different care facilities are poorly described. We evaluated the relationship between hospital surgical volume and academic hospital status with these surgical outcomes and overall survival (OS). METHODS AND MATERIALS Patients with nonmetastatic urothelial carcinoma of the bladder who underwent RC were identified from the National Cancer Database (2004-2013). Treatment centers were categorized as academic (ACC) and community cancer centers (CCC). Logistic regression was used to identify factors associated with PSM status and LNY, and a multivariate Cox proportional hazards model was used to determine factors associated with OS. RESULTS In our cohort, 39,274 patients underwent RC. A lower proportion of PSMs (10% vs.12%; P<0.001) and higher median LNY (14 vs. 8, P<0.001) was observed at ACCs compared to CCCs. On logistic regression, there were lower odds of PSM (OR = 0.89, 95% CI: 0.81-0.97) and higher odds of LNY ≥ 10 nodes (OR = 1.84, 95% CI: 1.74-1.96) among patients at ACCs compared to CCCs. Cox proportional hazards analysis demonstrated benefit to OS at high-volume centers (HR = 0.91, 95% CI: 0.87-0.95) but not based on ACC designation. The OS advantage at high-volume centers is attenuated (HR = 0.95, 95% CI: 0.91-0.99) by PSM status and LNY. CONCLUSIONS ACCs demonstrate improved surgical outcomes following RC, and a survival advantage attributable to high surgical volume is identified. Centralization of care may lead to improved outcomes in this lethal malignancy.

Multi-institutional Evaluation of Elective Nodal Irradiation and/or Androgen Deprivation Therapy with Postprostatectomy Salvage Radiotherapy for Prostate Cancer

BACKGROUND Outcomes with postprostatectomy salvage radiation therapy (SRT) are not ideal. Little evidence exists regarding potential benefits of adding whole pelvic radiation therapy (WPRT) alone or in combination with androgen deprivation therapy (ADT). OBJECTIVE To explore whether WPRT and/or ADT added to prostate bed radiation therapy (PBRT) improves freedom from biochemical failure (FFBF) or distant metastases (DM). DESIGN, SETTING, AND PARTICIPANTS A database was compiled from 10 academic institutions of patients with postprostatectomy prostate-specific antigen (PSA) >0.01 ng/ml; pT1-4, Nx/0, cM0; and Gleason score (GS) ≥7 treated between 1987 and 2013. Median follow-up was 51 mo. INTERVENTIONS WPRT and/or ADT in addition to PBRT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES FFBF and DM were calculated using cumulative incidence estimation. Multivariable analysis (MVA) utilized cumulative incidence regression. RESULTS AND LIMITATION Median pre-SRT PSA was 0.5 ng/ml for 1861 patients. Median follow-up for patients not experiencing biochemical failure (BF) was 55 mo. MVA showed increased BF for PBRT versus WPRT (hazard ratio [HR] 1.82, p<0.001) and no ADT versus ADT (HR 1.70, p<0.001). WPRT was associated with a 5-yr FFBF of 62% versus 49% (p<0.001) for PBRT. ADT use was associated with improved 5-yr FFBF (55% vs 50%, p=0.012). No significant differences in DM cumulative incidence were found. CONCLUSIONS For patients with GS ≥7 receiving SRT, clinicians should weigh FFBF benefits of WPRT and ADT against toxicities. Future studies should explore the impact of WPRT on quality of life, clinical progression, and overall survival. PATIENT SUMMARY We evaluated patients with prostate cancer treated with radiation after surgery to remove the prostate. Both radiation to the pelvic lymph nodes and suppression of testosterone lowered the chance of increasing prostate-specific antigen (a marker for cancer returning).

Establishing a Multidisciplinary Approach to the Management of Neurologic Disease Affecting the Urinary Tract

Neurologic diseases often affect the urinary tract and may be congential or acquired. The progressive nature of many neurologic diseases necessitates routine surveillance and treatment with a multidisciplinary approach. Urologic treatments may interact with pharmacologic or procedural interventions planned by other specialists, mandating close coordination of care and communication among providers. Primary care and nursing often can serve as the quarterbacks of the multidisciplinary team by identifying when a slowly progressive condition warrants further investigation and management by specialists.

MP63-19 THE VALUE OF URODYNAMICS PRIOR TO SACRAL NEUROMODULATION IN MEN

INTRODUCTION AND OBJECTIVES: Sacral neuromodulation (SNM) is an effective therapy for non-obstructive urinary retention, refractory urgency/frequency and urgency incontinence, however it may be underutilized in men. There is a dearth of literature on SNM in men, as most male lower urinary tract symptoms (LUTS) research focuses on medical therapy and bladder outlet procedures, offering little guidance about SNM in men. To what extent UDS can yield diagnostic clarity in male LUTS and its role in predicting SNM success in men is unknown. Herein, we analyze how UDS findings relate to SNS utilization in men. METHODS: A retrospective review of men undergoing SNM procedures from 2011-2015 at our institution was performed. Demographics, comorbidities, prior urologic treatments, SNM indication, and SNM utilization were assessed. Patients were stratified according to UDS 12 months before SNM (+UDS) vs. no UDS testing (-UDS). Descriptive statistics characterized the groups, T-test or chi-square tests were used where appropriate, and logistic regression was used to identify clinical and UDS parameters related to SNM outcomes. RESULTS: 56 men underwent SNM therapy and 28 had UDS within the prior year. UDS+ and UDSmen were similar in age and co-morbid conditions. On average, +UDS men had a greater BMI (30.4+6.5 v 27.3+4.6, p 0.045). Rates of prior transurethral prostate procedures were not significantly different (17.9% v 25%) between the groups. Most (N1⁄453) men underwent staged implant, though 3 (+UDS N1⁄42, -UDS N1⁄41) had peripheral nerve evaluation (PNE). All PNE trials were successful, while rates of Stage 1 success (80.8% v 63.0%, p 0.22) and Stage 2 completion (95.2% v 94.1%, p 1.00) did not differ between +UDS or -UDS men. Device revision (21.4% vs. 25%, p 0.75) and explant (17.9% v 14.5%, p 1.00) rates also did not differ by +UDS or -UDS. No stress urinary incontinence (N1⁄40) was noted on UDS in any patient, but detrusor overactivity was present in 50% (N1⁄414) with urgency urinary incontinence in 25% (N1⁄47). UDS findings of obstruction (N1⁄41), poor compliance (N1⁄41), and hypocontracility (N1⁄41) were rare. Rates of Stage 1 success, Stage 2 completion, device revision, and device explant did not differ in the presence or absence of UDS-proven pathology CONCLUSIONS: Sacral nerve stimulation is a feasible treatment for men with refractory lower urinary tract symptoms. Neither the performance of urodynamics nor the presence of urodynamically-proven pathology was associated with greater likelihood of progression to stage 2, device revision or explant. Our findings suggest that SNM may be safely and effectively utilized in men without preoperative urodynamics.

Secondary Urethral Malignancies Following Prostate Brachytherapy

OBJECTIVE To understand urethral secondary malignancies among patients treated with brachytherapy (BRT) for primary prostate cancer. PATIENTS AND METHODS Institutional retrospective review identified 13 patients evaluated from 2003 to 2014 with urethral cancer and history of BRT monotherapy for prostate cancer. All patients were biochemically free of their primary disease and radiation-associated secondary malignancies (RASMs) were confirmed pathologically to be histologically distinct from primary tumor. BRT characteristics, patient age, presentation, staging workup, and clinical course were evaluated. RESULTS The mean time from BRT to presenting symptoms of hematuria, urinary retention, and/or renal failure was 71 months. Symptom onset to RASM diagnosis interval was 24 months. Mean time from BRT to RASM diagnosis was 95 months. Eighty-five percent of patients had an undetectable prostate-specific antigen level (<0.2 ng/mL) at last follow-up. Types of RASM included sarcomatoid carcinoma (6), small cell carcinoma (2), urothelial carcinoma with squamous differentiation (2), squamous cell carcinoma (1), rhabdomyosarcoma (1), and urothelial carcinoma (1). A majority of patients were diagnosed with advanced disease with either distant metastases (54%) or local progression (23%). Ten patients died during this study period with median time to death after RASM diagnosis of 6 months. CONCLUSION RASMs localized to the posterior urethra displayed advanced disease and high mortality rates. Refractory lower urinary tract symptoms, hematuria, and history of prostate BRT should raise suspicion for urethral RASMs. Further studies are warranted to determine patient and disease characteristics that correlate with disease-specific mortality of secondary urethral malignancies.

Comparative Effectiveness of Surgical Treatments for Small Renal Masses

In the management of small renal masses (SRMs), treatment options include partial nephrectomy (PN), radical nephrectomy (RN), ablation, renal biopsy, and active surveillance. Large series retrospective and meta-analyses demonstrate PN may confer greater preservation of renal function, overall survival, and equivalent cancer control when compared with RN. As newer therapies emerge, we should critically evaluate the risks and benefits associated with the surgical management of SRMs among patients with competing comorbidities, complex tumors, and high-risk disease. Among younger patients with SRMs amenable to resection, optimization of postoperative patient health should be prioritized.

MP93-10 URINARY, BOWEL, AND SEXUAL FUNCTION AT 2 YEARS FOLLOWING MANAGEMENT OF LOCALIZED PROSTATE CANCER

the Expanded Prostate Index Composite (EPIC-26), UCLA Prostate Cancer Index (PCI), Sexual Health Inventory for Men (SHIM) and International Prostate Symptom Scale (IPSS) questionnaires. We investigated several methods to convert scores between questionnaires. RESULTS: Conversion between EPIC and PCI urinary and sexual function subscales is best achieved using only the subset of questions that were asked on both questionnaires. This means that sexual function focuses on erectile function and does not include libido, which is include only on the PCI. For the conversion between EPIC or PCI erectile function scores and the SHIM scores, we defined equivalent thresholds of poor, intermediate or good function respectively: EPIC/PCI 0 40 and SHIM 1-7; EPIC/PCI 41 59 and SHIM 8-16; EPIC/ PCI 60 100 and SHIM 17-25. Urinary continence scores are highly correlated between PCI and EPIC (r1⁄40.94). Multiple attempts were made to compare IPSS with EPIC and PCI, but after investigation, no comparison was possible due to differences in domains addressed by these questionnaires. Therefore, we do not believe a conversion between IPSS and either PCI or EPIC is appropriate. CONCLUSIONS: We have introduced methods for converting scores between the EPIC, PCI and SHIM questionnaires. While these conversion methods may introduce a minor amount of imprecision, such imprecision is dwarfed by other factors (such as case mix and statistical imprecision). Our methods represent the best available tools for combining and comparing patient-reported outcomes assessed using different instruments.