Faculty Bibliography

BACKGROUND/UNASSIGNED:Phosphodiesterase type 5 (PDE5) inhibitors are used to treat erectile dysfunction, but their cost can limit access. AIM/UNASSIGNED:This study examines PDE5 inhibitors pricing and demographic data across rural and urban New York State (NYS) counties, as well as small, large, and online pharmacies. METHODS/UNASSIGNED:-tests, Wilcoxon rank-sum, and Kruskal-Wallis tests were performed using R Version 4.4.1 (2024-06-14). OUTCOMES/UNASSIGNED:The cash price of the PDE5 inhibitors across various pharmacy chain types and county types. RESULTS/UNASSIGNED: = .177). CLINICAL TRANSLATION/UNASSIGNED:This study aims to highlight the pricing variability of PDE5 inhibitors to help patients identify cost-effective options to circumvent potential financial barriers. STRENGTHS AND LIMITATIONS/UNASSIGNED:This study was the first to examine PDE5 inhibitors pricing specifically within rural populations while also providing a comparative analysis of pricing differences between small and large pharmacy chains serving these communities. The study's limitations include a relatively small sample size of rural and small chain pharmacies resulting in power levels of 75% and 69%, respectively, which may impact the generalizability of the findings. CONCLUSION/UNASSIGNED:Enhancing drug price transparency for PDE5 inhibitors is vital for increasing access and pricing flexibility.

OBJECTIVES/UNASSIGNED:To evaluate the incidence and degree of rectal wall infiltration (RWI) of spacer gel used during prostate radiotherapy among two practitioners experienced in using rectal spacers. MATERIALS AND METHODS/UNASSIGNED:Consecutive patients with prostate cancer who received prostate radiotherapy after hydrogel rectal spacer insertion in August 2023-August 2024 by two experienced practitioners were retrospectively included. Post-implant magnetic resonance imaging examinations were evaluated by two radiologists for RWI: 0 (no abnormality), 1 (rectal wall edema), 2 (superficial RWI), and 3 (deep RWI). Scores 2-3 were considered positive for RWI and their location and degree of RWI (radial, longitudinal, and circumferential) were also categorized. Inter-reader agreement was assessed with Cohen's Kappa. RESULTS/UNASSIGNED:215 men were included. Agreement was substantial between the radiologists for RWI scores (Kappa, 0.697; 95% confidence interval, 0.594-0.800). RWI scores were 0 in 80.5% (173/215), 1 in 7.9% (17/215), 2 in 10.7% (23/215), and, 3 in 0.9% (2/215) of the men. Altogether, RWI was present (scores 2-3) in 11.6% (25/215), most commonly in the mid-gland and apex with median radial, longitudinal, and circumferential involvement of 3.2 mm, 8.6 mm, and 11.5%. None of these patients demonstrated any significant rectal toxicity. CONCLUSION/UNASSIGNED:RWI was very uncommon for experienced practitioners. The degree of RWI was focal and not associated with increased complications.

Androgen deprivation therapy (ADT) is a mainstay treatment for metastatic prostate cancer, improving progression-free survival. ADT suppresses the production of testosterone and reduces circulating levels of the hormone. Luteinizing hormone-releasing hormone (LH-RH) agonists are the most commonly used ADT modality. They can be given alone or in combination with androgen synthesis inhibitors or androgen receptor antagonists. An estimated 40% of prostate cancer patients will receive ADT as part of their therapy during their lifetime. However, ADT has numerous adverse effects, including an increased cardiovascular risk that impacts quality of life. Relugolix is an alternative form of ADT. It is the only oral gonadotropin-releasing hormone antagonist, circumventing injection site reactions, making it easier for patients to take, and thus increasing compliance. Testosterone suppression with relugolix is excellent and testosterone recovery after discontinuation is rapid. This paper reviews the ADT and anti-androgen treatment options for men with prostate cancer and the cardiovascular effects of these therapies. There is accumulating evidence that cardiovascular risk with relugolix is lower than with other ADT medications and also lower than with androgen synthesis inhibitors and androgen receptor antagonists. This paper provides insight into the use of different ADT regimens based on the cardiovascular status and circumstances. It explores strategies to mitigate negative cardiovascular consequences and highlights the need for further study.

BACKGROUND:to date, no standardized, evidence-based follow-up schemes exist for the monitoring of patients who underwent focal therapy (FT) and expert centers rely mainly on their own experience and/or institutional protocols. We aimed to perform a comprehensive review of the most advantageous follow-up strategies and their rationale after FT for prostate cancer (PCa). METHODS:a narrative review of the literature was conducted to investigate different follow-up protocols of FT for PCa. Outcomes of interest were post-ablation oncological and functional outcomes and complications. RESULTS:Oncological success after FT was generally defined as the biopsy-confirmed absence of clinically significant PCa in the treated zone. De novo PCa in the untreated area usually reflects an inaccurate patient selection and should be treated as primary PCa. During follow-up, oncological outcomes should be evaluated with periodic PSA, multiparametric MRI and prostate biopsy. The use of PSA derivatives and new biomarkers is still controversial and therefore not recommended. The first MRI after FT should be performed between 6-12 months to avoid ablation-related artifacts and diagnostic delay in case of FT failure. Other imaging modalities, such as PSMA PET/CT scan, are promising but still need to be validated in the post-FT setting. A 12-month "for-protocol" prostate biopsy, including targeted and systematic biopsy, was generally considered the preferred biopsy method to rule out tumor persistence/recurrence. Subsequent mpMRIs and biopsies should follow a risk-adapted approach depending on the clinical scenario. Functional outcomes should be periodically assessed using validated questionnaires within the first year, when typically recover to a new baseline. Complications, despite uncommon, should be strictly monitored mainly in the first month. CONCLUSIONS:FT follow-up is a multifaceted process involving clinical, radiological, and histological assessment. Studies evaluating the impact of different follow-up strategies and ideal timings are needed to produce standardized protocols following FT.

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:Percentage of positive cores involved on a systemic prostate biopsy has been established as a risk factor for adverse oncologic outcomes and is a National Comprehensive Cancer Network (NCCN) independent parameter for unfavorable intermediate-risk disease. Most data from a radiation standpoint was published in an era of conventional fractionation. We explore whether the higher biological dose delivered with SBRT can mitigate this risk factor. METHODS:A large single institutional database was interrogated to identify all patients diagnosed with localized prostate cancer (PCa) treated with 5-fraction SBRT without ADT. Pathology results were reviewed to determine detailed core involvement as well as Gleason score (GS). High-volume biopsy core involvement was defined as ≥ 50%. Weighted Gleason core involvement was reviewed, giving higher weight to higher-grade cancer. The PSA kinetics and oncologic outcomes were analyzed for association with core involvement. RESULTS:From 2009 to 2018, 1590 patients were identified who underwent SBRT for localized PCa. High-volume core involvement was a relatively rare event observed in 19% of our cohort, which was observed more in patients with small prostates (p < 0.0001) and/or intermediate-risk disease (p = 0.005). Higher PSA nadir was observed in those patients with low-volume core involvement within the intermediate-risk cohort (p = 0.004), which was confirmed when core involvement was analyzed as a continuous variable weighted by Gleason score (p = 0.049). High-volume core involvement was not associated with biochemical progression (p = 0.234). CONCLUSIONS:With a median follow-up of over 4 years, biochemical progression was not associated with pretreatment high-volume core involvement for patients treated with 5-fraction SBRT alone. In the era of prostate SBRT and MRI-directed prostate biopsies, the use of high-volume core involvement as an independent predictor of unfavorable intermediate risk disease should be revisited.

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.

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.

Prostate cancer is the second leading cause of cancer death in men in the United States. Androgen deprivation therapy (ADT) is currently the primary treatment for metastatic prostate cancer, and some studies have shown that the use of anti-androgen drugs is related to a reduction in cognitive function, mood changes, diminished quality of life, dementia, and possibly Alzheimer's disease. ADT has potential physiological effects such as a reduction in white matter integrity and a negative impact on hypothalamic functions due to the lowering of testosterone levels or the blockade of downstream androgen receptor signaling by first- and second-generation anti-androgen drugs. A comparative analysis of prostate cancer patients undergoing ADT and Alzheimer patients identified over 30 shared genes, illustrating common ground for the mechanistic underpinning of the symptomatology. The purpose of this review was to investigate the effects of ADT on cognitive function, mood, and quality of life, as well as to analyze the relationship between ADT and Alzheimer's disease. The evaluation of prostate cancer patient cognitive ability via neurocognitive testing is described. Future studies should further explore the connection among cognitive deficits, mood disturbances, and the physiological changes that occur when hormonal balance is altered.

CONTEXT/BACKGROUND:Whole-gland ablation is a feasible and effective minimally invasive treatment for localized prostate cancer (PCa). Previous systematic reviews supported evidence for favorable functional outcomes, but oncological outcomes were inconclusive owing to limited follow-up. OBJECTIVE:To evaluate the real-world data on the mid- to long-term oncological and functional outcomes of whole-gland cryoablation and high-intensity focused ultrasound (HIFU) in patients with clinically localized PCa, and to provide expert recommendations and commentary on these findings. EVIDENCE ACQUISITION/METHODS:We performed a systematic review of PubMed, Embase, and Cochrane Library publications through February 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. As endpoints, baseline clinical characteristics, and oncological and functional outcomes were assessed. To estimate the pooled prevalence of oncological, functional, and toxicity outcomes, and to quantify and explain the heterogeneity, random-effect meta-analyses and meta-regression analyses were performed. EVIDENCE SYNTHESIS/RESULTS:Twenty-nine studies were identified, including 14 on cryoablation and 15 on HIFU with a median follow-up of 72 mo. Most of the studies were retrospective (n = 23), with IDEAL (idea, development, exploration, assessment, and long-term study) stage 2b (n = 20) being most common. Biochemical recurrence-free survival, cancer-specific survival, overall survival, recurrence-free survival, and metastasis-free survival rates at 10 yr were 58%, 96%, 63%, 71-79%, and 84%, respectively. Erectile function was preserved in 37% of cases, and overall pad-free continence was achieved in 96% of cases, with a 1-yr rate of 97.4-98.8%. The rates of stricture, urinary retention, urinary tract infection, rectourethral fistula, and sepsis were observed to be 11%, 9.5%, 8%, 0.7%, and 0.8%, respectively. CONCLUSIONS:The mid- to long-term real-world data, and the safety profiles of cryoablation and HIFU are sound to support and be offered as primary treatment for appropriate patients with localized PCa. When compared with other existing treatment modalities for PCa, these ablative therapies provide nearly equivalent intermediate- to long-term oncological and toxicity outcomes, as well as excellent pad-free continence rates in the primary setting. This real-world clinical evidence provides long-term oncological and functional outcomes that enhance shared decision-making when balancing risks and expected outcomes that reflect patient preferences and values. PATIENT SUMMARY/RESULTS:Cryoablation and high-intensity focused ultrasound are minimally invasive treatments available to selectively treat localized prostate cancer, considering their nearly comparable intermediate- to long term cancer control and preservation of urinary continence to other radical treatments in the primary setting. However, a well-informed decision should be made based on one's values and preferences.