Faculty Bibliography

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.

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.

PURPOSE:We evaluated 3-year oncologic outcomes following primary partial gland cryoablation. MATERIALS AND METHODS:Men with unilateral intermediate-risk prostate cancer undergoing primary partial gland cryoablation since March 2017 enrolled in a prospective outcome registry. The postablation protocol for all men included surveillance prostate biopsy at 2 years postablation and reflex prostate biopsy for cases with high suspicion of recurrence (eg, progressive rise in PSA). Recurrence of clinically significant prostate cancer was defined as any Gleason grade group ≥2 disease on postablation biopsy. Freedom from failure represented no whole gland salvage treatment, metastatic prostate cancer, or prostate cancer mortality. Freedom from recurrence and freedom from failure were characterized using nonparametric maximum likelihood estimators. RESULTS:A total of 132 men had at least 24 months of follow-up data. Biopsies identified clinically significant prostate cancer in 12 men. At 36 months, model-estimated rates of freedom from recurrence of in-field, out-of-field, and overall clinically significant cancer were 97% (95% CI: 92-100), 87% (95% CI: 80-94), and 86% (95% CI: 78-93), respectively. The model-estimated proportion with freedom from failure at 36 months was 97% (95% CI: 93-100). CONCLUSIONS:The low in-field cancer detection rate at 3 years indicates successful ablation of localized cancers. Conversely, our observed out-of-field detection rate highlights the need for continued surveillance following partial gland cryoablation. Many of these recurrences exhibited very low volume of clinically significant disease below the detection threshold of multiparametric MRI, suggesting a limited role for multiparametric MRI in detecting clinically significant recurrences at 2 years. These findings emphasize the need for long-term surveillance and identification of predictors of clinically significant prostate cancer recurrences to guide biopsy timing.

BACKGROUND:Evading immune surveillance is a hallmark for the development of multiple cancer types. Whether immune evasion contributes to the pathogenesis of high-grade prostate cancer (HGPCa) remains an area of active inquiry. METHODS:Through single-cell RNA sequencing and multicolor flow cytometry of freshly isolated prostatectomy specimens and matched peripheral blood, we aimed to characterize the tumor immune microenvironment (TME) of localized prostate cancer (PCa), including HGPCa and low-grade prostate cancer (LGPCa). RESULTS: TILs. The PCa TME was infiltrated by macrophages but these did not clearly cluster by M1 and M2 markers. CONCLUSIONS:T cell exhaustion in localized PCa, a finding enriched in HGPCa relative to LGPCa. These studies suggest a possible link between the clinical-pathologic risk of PCa and the associated TME. Our results have implications for our understanding of the immunologic mechanisms of PCa pathogenesis and the implementation of immunotherapy for localized PCa.

BACKGROUND:Magnetic resonance imaging (MRI)-targeted prostate biopsy has become an increasingly common method of diagnosing prostate cancer. A previous study from our institution demonstrated that the biopsy global Grade Group (gGG, aggregate GG of all positive cores) and highest Grade Group (hGG in any core) both show substantial concordance with the Grade Group at radical prostatectomy (RPGG) while the discordance predominantly consists of upgrading in gGG and downgrading in hGG. We performed a larger cohort study focused on biopsy cases in which gGG and hGG differ, to determine their relative concordance with RPGG. METHODS:We conducted a retrospective review of radical prostatectomy specimens with prior MRI-targeted biopsies from our institution between 2016 and 2020. Separate gGG and hGG were assigned to each MRI-targeted lesion. Targeted lesions with different gGG versus hGG were segregated from those with identical gGG and hGG. The concordance of biopsy GG with RPGG was evaluated using κ coefficient analysis. RESULTS:Of the 489 lesions with MRI-targeted biopsies, 82 (17%) differed in gGG versus hGG. The gGG of 46 (56%), 33 (40%), and 3 (4%) lesions were unchanged, upgraded, and downgraded at radical prostatectomy, respectively (κ= 0.302, weighted κ = 0.334). The hGG of 24 (29%), 9 (11%), and 49 (60%) lesions were unchanged, upgraded, and downgraded at radical prostatectomy, respectively (κ = 0.040, weighted κ = 0.198). When stratified by the biopsy GG, gGG showed the highest concordance in GG2 (61%) and GG3 (54%) lesions. The hGG resulted in substantial downgrading (60%) with less optimal concordance regardless of the biopsy GG. Neither the prebiopsy prostate specific antigen level nor the PI-RADS score was predictive of upgrading of gGG. CONCLUSIONS:When gGG and hGG differ, gGG method more accurately predicts the RPGG than hGG, particularly in GG2 and GG3 lesions which comprised the majority of targeted lesions.

OBJECTIVE:Our purpose was to critically evaluate time dependent sexual function following primary partial gland cryo-ablation (PGCA) stratified according to baseline erectile function. METHODS:Between March 2017 and March 2022, all men undergoing primary PGCA by two surgeons were enrolled in an IRB approved outcomes registry. All subjects with PIRADS 2-5 lesion concordant with unilateral GGG 1-3 disease, no gross extra-prostatic extension on mpMRI, GGG >1 contralateral to the ROI, or distal apical disease on mpMRI were enrolled. Patients completed the Sexual Health Inventory for Men (SHIM) scale at baseline, 6, and 24 months. Men were stratified by baseline erectile function. Men with SHIM Score < 8 were excluded. Ability to sustain erection (aka "potency") was defined as a score of 3 or greater on question 2 of the SHIM index. Median SHIM scores and the proportion of men reporting "potency" at baseline, 6, and 24 months was recorded with comparisons between each timepoint. A univariate analysis was used to determine if clinical factors were associated with loss of "potency" at 24 months. RESULTS:106 men met the inclusion criteria. There was a statistically significant decrease in the mean SHIM scores for the entire cohort between baseline to 6 months and baseline to 24 months. SHIM scores increased significantly for the total cohort between 6 and 24 months. "Potency" was preserved in 70% at 24 months. CONCLUSIONS:Those patients most likely to exhibit a decrease in sexual function have moderate ED at baseline. Only baseline ED was shown to predict preservation of "potency".