Faculty Bibliography

PURPOSE/OBJECTIVE:Both MRI and PSMA PET/CT are often utilized for staging of intermediate-risk (IR) and high-risk (HR) prostate cancer (PCa). Recent studies found that PSMA PET/CT was superior to MRI in correctly identifying final pathological tumor stage, dominant nodule, extraprostatic extension (EPE), and small areas of clinically significant PCa. We sought to determine if PSMA PET/CT was superior to MRI in both locoregional staging of PCa and potential focal therapy planning. METHODS:We retrospectively analyzed our prospectively collected, IRB-approved database of all patients who underwent prostatectomy at one institution between 10/1/2019-2/29/2024. Patients were excluded if they did not pre-operatively undergo both MRI and PSMA PET/CT. 2 × 2 tables were used to compare each modality to the "gold standard" of prostatectomy specimen in both the proper detection of laterality and presence of EPE. Sensitivities and specificities were compared using a chi-squared test. HR v. IR groups were compared using a Wilcoxon rank sum test for continuous variables and Fisher's exact test for categorical variables. Results were considered significant at p < 0.05. RESULTS:580 patients underwent prostatectomy within the specified timeframe. 78 patients met inclusion criteria. MRI was more sensitive in the detection of EPE than PSMA PET/CT (23.5% v. 7.8%, p = 0.0294). MRI and PSMA PET/CT were similar in the specificity of EPE detection. In the identification of laterality, MRI was more specific (86.7% v. 56.7%, p = 0.0099), while sensitivities were similar between the modalities. CONCLUSIONS:MRI was superior to PSMA PET/CT in the proper detection of both EPE and laterality in patients with IR and HR PCa.

PURPOSE/OBJECTIVE:Pelvic nodal irradiation is often used for high-risk prostate adenocarcinoma. A commonly used alternative to low dose rate (LDR) brachytherapy, a 3-fraction SBRT boost with fiducial tracking may allow for better coverage of extracapsular extension and macroscopic seminal vesicle invasion. This study evaluates the practical impact of prior pelvic nodal irradiation on fiducial tracking during a subsequent 3-fraction robotic stereotactic body radiation therapy (SBRT) boost for high-risk prostate cancer and compares these outcomes to a cohort of patients undergoing definitive 5-fraction SBRT. METHODS:In this institutional analysis, we prospectively collected fiducial tracking data for patients receiving a 3-fraction boost to the prostate and seminal vesicles after conventional nodal radiation. We also identified patients treated with 5-fraction SBRT with a low risk of nodal involvement. Monte Carlo estimates of the Fisher's Exact Test assessed fiducial tracking loss. Continuous variables within the 5- and 3-fraction cohorts were compared using the Mann-Whitney Test. Changes in fiducial tracking and their association with pre-treatment factors were analyzed through the Kruskal-Wallis test and Monte Carlo for tracking patterns, and Spearman Correlation Coefficient and Mann-Whitney Test for deviations in tracking over 5 fractions. RESULTS:A total of 405 patients were treated from April 2021 to September 2023 with: (1) 5-fraction SBRT (n = 309, 76%), and (2) 3-fraction boost after nodal irradiation (n = 96, 24%). There was no significant fiducial tracking loss over the three-fraction boost treatment regimen that proceeded nodal treatment (p = 0.63). However, there was a significant (p < 0.001) loss of fiducial tracking fidelity as demonstrated by progressive loss of one tracked fiducial over 5-fractions. There was significantly more volatility observed in the 5-fraction versus 3-fraction boost treatment (median volatility 2.4 vs. 0.0, p < 0.001). There were no significant associations between fiducial tracking, independently for 3- or 5-fractions, using either analysis method or volatility for ADT, time from fiducial placement to SBRT, CTV, and QOD vs. daily SBRT. CONCLUSIONS:Pelvic nodal treatment does not affect the quantity/quality of fiducial tracking in 3-fraction treatments. However, 5-fraction treatments showed a progressive loss and increased volatility in fiducial tracking over time. No pre-treatment factors significantly influenced fiducial tracking changes in either cohort, though ADT use trended towards increased volatility in the 5-fraction group. With a minimum of 4 fiducials placed for treatment, the loss/volatility of a single fiducial had no clinical impact on the tracking system.

PURPOSE/UNASSIGNED:In QUILT-3.032, the efficacy of IL-15 receptor agonist, nogapendekin alfa inbakicept (NAI) in combination with BCG for BCG-unresponsive high-grade papillary-only non-muscle invasive bladder cancer (NMIBC) was assessed. Herein we report the 36-month follow-up among participants with BCG-unresponsive papillary disease (Cohort B). MATERIALS AND METHODS/UNASSIGNED:NCT03022825 is an open-label, multi-center study with BCG-unresponsive high-grade Ta/T1 papillary NMIBC who received 400μg NAI plus 50mg BCG intravesically weekly for six consecutive weeks. The primary endpoint is disease-free survival (DFS) at 12-months. Progression-free survival (PFS), disease-specific survival (DSS), and cystectomy avoidance were assessed. Treatment-related adverse events (TRAEs) were assessed. RESULTS/UNASSIGNED:At July 15, 2024 data cutoff, the DFS rates at 12-, 24-, and 36-months were 58.2% (95% CI 46.6, 68.2), 52.1% (95% CI 40.3, 62.7), and 38.2% (95% CI 25.6, 50.6), respectively. The PFS rates at 12- and 36-months were 94.9% (95% CI 86.9, 98.0) and 83.1% (95% CI 69.5, 91.0). The DSS rates at 12- and 36-months were 98.7% (95% CI 91.4, 99.8) and 96.0% (95% CI 88.2, 98.7). The median DSS has not been reached. Cystectomy avoidance rates at 12- and 36-months were 92.2% (95% CI 83.4, 96.4) and 81.8% (95% CI 68.1, 90.1), with median time to cystectomy not reached. Most TRAEs were grade 1-2 (61%) with 3% grade 3, and no grade 4-5. CONCLUSIONS/UNASSIGNED:The 12- and 36-month DFS, PFS, DSS, and cystectomy avoidance rates demonstrate the effectiveness and safety of NAI plus BCG in the management of BCG-unresponsive papillary disease.

PURPOSE/OBJECTIVE:To assess the ability to deliver full thickness bladder wall cryoablation via a cystoscopic approach using a new closed loop 6Fr cryocatheter and thermal dose controlled protocol. MATERIALS AND METHODS/METHODS:Evaluations were conducted using a chronic porcine model wherein 10 lesions/animal were created throughout the bladder (bladder wall, trigone region, ureteral orifice and distal ureter). A 6Fr cryocatheter was passed through the working channel of a flexible cystoscope. Single 1 and 1.5min freeze protocols in a saline environment were evaluated and resultant lesion size was determined. A laparoscopic approach was utilized to visualize the transmural extension of the ice propagation. RESULTS:Studies demonstrated the generation of transmural lesions characterized by full thickness histological necrosis following freezing for 1.5min regardless of tissue thickness (range: 2mm to 12mm). All animals were found to have good overall health (maintained weight, appetite, mobility, energy levels) throughout the recovery period. No significant deviations were noted in CBC and serum chemistry bloodwork with the exception of elevated Creatine Kinase levels. Importantly, no fistulas or perforations were noted. CONCLUSIONS:The cryocatheter was able to rapidly and effectively freeze the bladder wall via a cystoscopic approach. The results showed the ability to consistently ablate a ~1cm diameter and up to 1.2cm deep using a single 1.5min freeze protocol. Analysis of the ablation efficacy revealed ~80% destruction within the frozen mass. Although further testing and refinement are needed, these studies demonstrate the potential of this new approach to provide a next-generation strategy for the treatment of bladder cancer.

PURPOSE/OBJECTIVE:Historically, toxicity concerns have existed in patients with large prostate glands treated with radiation therapy, particularly brachytherapy. There are questions whether this risk extends to stereotactic body radiation therapy (SBRT). In this retrospective review, we examine clinical outcomes of patients with prostate glands ≥100 cc treated curatively with SBRT. METHODS AND MATERIALS/METHODS:We retrospectively analyzed a large institutional database to identify patients with histologically confirmed localized prostate cancer in glands ≥100 cc, who were treated with definitive-robotic SBRT. Prostate volume (PV) was determined by treatment planning magnetic resonance imaging. Toxicity was measured using Common Terminology Criteria for Adverse Events, version 5.0. Many patients received the Expanded Prostate Cancer Index Composite Quality of Life questionnaires. Minimum follow-up (FU) was 2 years. RESULTS:Seventy-one patients were identified with PV ≥100 cc. Most had grade group (GG) 1 or 2 (41% and 37%, respectively) disease. All patients received a total dose of 3500 to 3625 cGy in 5 fractions. A minority (27%) received androgen deprivation therapy (ADT), which was used for gland size downsizing in only 10% of cases. Nearly half (45%) were taking GU medications for urinary dysfunction before RT. Median toxicity FU was 4.0 years. Two-year rates of grade 1+ genitourinary (GU), grade 1+ gastrointestinal (GI), and grade 2+ GU toxicity were 43.5%, 15.9%, and 30.4%, respectively. Total grade 3 GU toxicities were very limited (2.8%). There were no grade 3 GI toxicities. On logistic regression analysis, pretreatment use of GU medications was significantly associated with increased rate of grade 2+ GU toxicity (odds ratio, 3.19; P = .024). Furthermore, PV (analyzed as a continuous variable) did not have an effect on toxicity, quality of life, or oncologic outcomes. CONCLUSIONS:With early FU, ultra large prostate glands do not portend increased risk of high-grade toxicity after SBRT but likely carry an elevated risk of low-grade GU toxicity.

PURPOSE/UNASSIGNED:Modern literature has demonstrated improvements in long-term biochemical outcomes with the use of prophylactic pelvic nodal irradiation followed by a brachytherapy boost in the management of high-risk prostate cancer. However, this comes at the cost of increased treatment-related toxicity. In this study, we explore the outcomes of the largest cohort to date, which uses a stereotactic body radiation therapy (SBRT) boost following pelvic nodal radiation for exclusively high-risk prostate cancer. METHODS AND MATERIALS/UNASSIGNED:A large institutional database was interrogated to identify all patients with high-risk clinical node-negative prostate cancer treated with conventionally fractionated radiotherapy to the pelvis followed by a robotic SBRT boost to the prostate and seminal vesicles. The boost was uniformly delivered over three fractions. Toxicity was measured using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Oncologic outcomes were assessed using the Kaplan-Meier method. Cox proportional hazard models were created to evaluate associations between pretreatment characteristics and clinical outcomes. RESULTS/UNASSIGNED:A total of 440 patients with a median age of 71 years were treated, the majority of whom were diagnosed with a grade group 4 or 5 disease. Pelvic nodal irradiation was delivered at a total dose of 4,500 cGy in 25 fractions, followed by a three-fraction SBRT boost. With an early median follow-up of 2.5 years, the crude incidence of grade 2+ genitourinary (GU) and gastrointestinal (GI) toxicity was 13% and 11%, respectively. Multivariate analysis revealed grade 2+ GU toxicity was associated with older age and a higher American Joint Committee on Cancer (AJCC) stage. Multivariate analysis revealed overall survival was associated with patient age and posttreatment prostate-specific antigen (PSA) nadir. CONCLUSION/UNASSIGNED:Utilization of an SBRT boost following pelvic nodal irradiation in the treatment of high-risk prostate cancer is oncologically effective with early follow-up and yields minimal high-grade toxicity. We demonstrate a 5-year freedom from biochemical recurrence (FFBCR) of over 83% with correspondingly limited grade 3+ GU and GI toxicity measured at 3.6% and 1.6%, respectively. Long-term follow-up is required to evaluate oncologic outcomes and late toxicity.

BACKGROUND:The purpose of this study is to analyze quality-of-life (QoL) metrics in men treated with focal cryoablation (FC) compared to active surveillance (AS) for localized PCa over a four-year follow-up period. We further investigated the effect of prostate size and minimum tumor temperature on QoL outcomes. METHODS:An Institutional Review Board-approved database was reviewed for patients who underwent FC or AS. QoL questionnaire responses were collected and scores were analyzed for differences between FC and AS, between prostate volume <50 cc and > 50 cc, and "cold" (<-78°C) and "warm" (>-78°C) tumor temperatures. RESULTS:148 AS and 60 FC patients were included. Compared to AS, no significant difference existed in urinary function measured by EPIC (p=0.593) and IPSS (p=0.241), bowel habits (p=0.370), or anxiety (p=0.672) across time post-FC. FC had significantly worse sexual function compared to AS measured by EPIC (p<0.0001) and IIEF (p<0.0001). Patients with prostate volume <50cc did not demonstrate differences between AS and FC in urinary function on EPIC (p=0.459) or IPSS (p=0.628) but FC patients had worse sexual function on EPIC (p<0.001) and IIEF (p<0.001). FC patients with a prostate volume >50cc had better urinary function measured by IPSS (p<0.05) and similar sexual function on EPIC (p=0.162) and IIEF (p=0.771) compared to AS. Urinary function over time measured by EPIC (0.825) and IPSS (p=0.658) was the same between AS, "warm", and "cold" FC groups. AS had significantly better sexual function than the "warm" and "cold" FC groups on EPIC (p<0.001) and IIEF (p<0.05). CONCLUSIONS:No differences were found in anxiety, urinary, or bowel function between AS and FC. Despite differences in sexual function, patients with larger prostates had no difference in sexual function and improved urinary function compared to AS. Future studies with larger cohorts are needed.

OBJECTIVE:The purpose of this study is to compare oncologic and functional outcomes of men with unilateral, localized PCa treated with stereotactic body radiotherapy (SBRT) versus focal cryoablation (FC). METHODS:Patients from our IRB-approved PCa database who underwent FC or SBRT and were eligible for both treatments were included. Patients with less than 1 year of follow-up or prior PCa treatment were excluded. The primary outcome was treatment failure, defined as salvage treatment or a Gleason group (GG) of ≥ 2 on post-treatment biopsy. Biochemical recurrence (BCR) was evaluated with Phoenix. Functional outcomes were based on EPIC surveys. Complications were categorized with the CTCAE 5.0. Outcomes were compared using descriptive statistics, univariate analyses, and Kaplan-Meier curve for failure-free survival (FFS) and BCR-free survival. P < 0.05 was significant. RESULTS:68 FC and 51 SBRT patients with a median age of 68 years (48-86) and a median follow-up time of 84 (70-101) months were included in this analysis. There was no difference in tumor risk (p = 0.47), GG (p = 0.20), or PSA (p = 0.70) among the two cohorts at baseline. At 7-year follow-up, no difference in FFS was found between the two cohorts (p = 0.70); however, significantly more FC patients had BCR (p < 0.001). At 48 months, no differences existed in urinary or bowel function; however, SBRT patients had significantly worse sexual function (p = 0.032). CONCLUSION/CONCLUSIONS:FC and SBRT are associated with similar oncologic and functional outcomes 7-year post-treatment. These results underscore the utility of FC and SBRT for the management of unilateral low-to-intermediate-risk PCa.

OBJECTIVE:To review quality-of-life (QoL) metrics between patients who underwent definitive stereotactic body radiotherapy (SBRT) versus active surveillance (AS) for management of low- to intermediate-risk prostate cancer (PCa). METHODS:A prospectively maintained PCa database was reviewed containing results of patient-reported QoL surveys. Patients with localized disease who chose AS or SBRT and completed at least one survey within four years of treatment were included. Patients who received salvage therapy were excluded. Survey results were compared across time using mixed-effects repeated measures analysis of covariance models that adjusted for factors significant in univariate analysis. A group x time interaction effect was examined to compare rate of change over time between AS and SBRT. P < 0.05 was significant. RESULTS:148 AS and 161 SBRT patients were included. Significantly more SBRT patients had intermediate-risk disease (p < 0.0001). AS had significantly worse sexual function compared to SBRT across time. While not significant, bowel function scores were lower for SBRT patients across time points. SBRT patients had significantly lower anxiety than AS patients at 24 months (p < 0.011) and 36 months (p < 0.010). Urinary function though worse in SBRT patients at 12 months in EPIC, was not significantly different in both groups across time points. CONCLUSION/CONCLUSIONS:SBRT patients have excellent QoL compared to AS with regard to anxiety post treatment. Though SBRT patients initially have worse urinary and bowel function than AS, scores were eventually similar in both cohorts by 48 months. SBRT patients have significantly worse sexual function post treatment. This study may help facilitate counseling in patients choosing PCa treatment.