Faculty Bibliography

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.

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.

Importance/UNASSIGNED:There is clinical equipoise for COVID-19 convalescent plasma (CCP) use in patients hospitalized with COVID-19. Objective/UNASSIGNED:To determine the safety and efficacy of CCP compared with placebo in hospitalized patients with COVID-19 receiving noninvasive supplemental oxygen. Design, Setting, and Participants/UNASSIGNED:CONTAIN COVID-19, a randomized, double-blind, placebo-controlled trial of CCP in hospitalized adults with COVID-19, was conducted at 21 US hospitals from April 17, 2020, to March 15, 2021. The trial enrolled 941 participants who were hospitalized for 3 or less days or presented 7 or less days after symptom onset and required noninvasive oxygen supplementation. Interventions/UNASSIGNED:A unit of approximately 250 mL of CCP or equivalent volume of placebo (normal saline). Main Outcomes and Measures/UNASSIGNED:The primary outcome was participant scores on the 11-point World Health Organization (WHO) Ordinal Scale for Clinical Improvement on day 14 after randomization; the secondary outcome was WHO scores determined on day 28. Subgroups were analyzed with respect to age, baseline WHO score, concomitant medications, symptom duration, CCP SARS-CoV-2 titer, baseline SARS-CoV-2 serostatus, and enrollment quarter. Outcomes were analyzed using a bayesian proportional cumulative odds model. Efficacy of CCP was defined as a cumulative adjusted odds ratio (cOR) less than 1 and a clinically meaningful effect as cOR less than 0.8. Results/UNASSIGNED:Of 941 participants randomized (473 to placebo and 468 to CCP), 556 were men (59.1%); median age was 63 years (IQR, 52-73); 373 (39.6%) were Hispanic and 132 (14.0%) were non-Hispanic Black. The cOR for the primary outcome adjusted for site, baseline risk, WHO score, age, sex, and symptom duration was 0.94 (95% credible interval [CrI], 0.75-1.18) with posterior probability (P[cOR<1] = 72%); the cOR for the secondary adjusted outcome was 0.92 (95% CrI, 0.74-1.16; P[cOR<1] = 76%). Exploratory subgroup analyses suggested heterogeneity of treatment effect: at day 28, cORs were 0.72 (95% CrI, 0.46-1.13; P[cOR<1] = 93%) for participants enrolled in April-June 2020 and 0.65 (95% CrI, 0.41 to 1.02; P[cOR<1] = 97%) for those not receiving remdesivir and not receiving corticosteroids at randomization. Median CCP SARS-CoV-2 neutralizing titer used in April to June 2020 was 1:175 (IQR, 76-379). Any adverse events (excluding transfusion reactions) were reported for 39 (8.2%) placebo recipients and 44 (9.4%) CCP recipients (P = .57). Transfusion reactions occurred in 2 (0.4) placebo recipients and 8 (1.7) CCP recipients (P = .06). Conclusions and Relevance/UNASSIGNED:In this trial, CCP did not meet the prespecified primary and secondary outcomes for CCP efficacy. However, high-titer CCP may have benefited participants early in the pandemic when remdesivir and corticosteroids were not in use. Trial Registration/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04364737.

The open approach to radical cystectomy continues to be accompanied by significant morbidity despite enhanced recovery protocols (ERP). Robotic assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) has become an increasingly popular technique for removal of aggressive bladder cancer and subsequent urinary diversion. Randomized clinical trials comparing the robotic and open techniques address the uncertainty surrounding oncological efficacy of the RARC and show that RARC is at least comparable to open radical cystectomy (ORC) in terms of oncologic adequacy and survival. Although RARC with ICUD is a technically challenging procedure, surgeons have noted ergonomic advantages while patients experience less blood loss and quicker time to recovery and to adjuvant chemotherapy (AC), if necessary. Even with these benefits, there is a paucity of data describing outcomes of ICUD. For those surgeons who have switched to ICUD, priority remains standardization of a protocol for the reconstructive component and for a safe transition from extracorporeal urinary diversion (ECUD) to ICUD. Additionally, there is a need for evidence of reduced financial toxicity for the patient, as well as more comprehensive cost-effectiveness analyses. The literature from this review represents 10 years of accumulating data on techniques and outcomes of RARC with ICUD.

This study aims to assess the impact of facility characteristics on measures of surgical quality (positive surgical margin rates and lymph-node yield) in patients undergoing robot-assisted (RARC) versus open (ORC) radical cystectomy using the National Cancer Database. Patients who received RC between the years of 2010-2013 were stratified according to surgery type (ORC vs. RARC), and corresponding patient and facility-level variables (facility type and volume) were assessed. Logistic regression models for procedure type, positive surgical margins (PSMs), and LN dissection (LND) rates were estimated. Radical cystectomies (ORC = 13,236, RARC = 3687) were performed more often in academic centers (58.3%) compared to community centers (31.6%). As facility volume increased, centers performed more LNDs during ORCs (p = 0.03) and the number of nodes retrieved increased in both ORC and RARC (ORC p < 0.001; RARC p < 0.0001). Increased facility volume also resulted in significantly fewer PSMs within the RARC cohort (p = 0.01). Comparison of ORC and RARC within each facility type cohort identified improved pathological metrics for RARC with fewer PSMs (p = 0.001) as well as increased LNDs (p < 0.0001) and median number of LNs retrieved (p < 0.0001), which suggests that RARC may facilitate comparative outcomes in community centers and academic centers. Overall, higher facility volume and robot-assisted surgery resulted in more favorable pathologic metrics compared to lower facility volume and ORC.

BACKGROUND: As the acceptance of cryoablative therapies for the treatment of non-metastatic cancers continues to grow, avenues for novel cryosurgical technologies and approaches have opened. Within the field of genitourinary tumors, cryosurgical treatments of bladder cancers remain largely investigational. Current modalities employ percutaneous needles or transurethral cryoballoons or sprays, and while results have been promising, each technology is limited to specific types and stages of cancers. OBJECTIVE: This study evaluated a new, self-contained transurethral cryocatheter, FrostBite-BC, for its potential to treat bladder cancer. METHODS: Thermal characteristics and ablative capacity were assessed using calorimetry, isothermal analyses, in vitro 3-dimensional tissue engineered models (TEMs), and a pilot in vivo porcine study. RESULTS: Isotherm assessment revealed surface temperatures below -20^â—¦ C within 9 sec. In vitro TEMs studies demonstrated attainment of ≤-20^â—¦ C at 6.1 mm and 8.2 mm in diameter following single and double 2 min freezes, respectively. Fluorescent imaging 24 hr post-thaw revealed uniform, ablative volumes of 326.2 mm³ and 397.9 mm³ following a single or double 2 min freeze. In vivo results demonstrated the consistent generation of ablative areas. Lesion depth was found to correlate with freeze time wherein 15 sec freezes resulted in ablation confined to the sub-mucosa and ≥30 sec full thickness ablation of the bladder wall. CONCLUSIONS: These studies demonstrate the potential of the FrostBite-BC cryocatheter as a treatment option for bladder cancer. Although preliminary, the outcomes of these studies were encouraging, and support the continued investigation into the potential of the FrostBite-BC cryocatheter as a next generation, minimally invasive cryoablative technology.