Faculty Bibliography

INTRODUCTION/BACKGROUND:We evaluate the rate of developing ciprofloxacin resistance in patients undergoing repeat prostate biopsies (PBx), associated risk factors, and impact on complications. MATERIALS AND METHODS/METHODS:We retrospectively evaluated pre-procedural rectal culture (RCx) data in men undergoing PBx from 1/1/2016 to 1/15/2021. Univariate and multivariate logistic regression were utilized to identify risk factors associated with development of antibiotic resistance. Complication rates were compared between ciprofloxacin-sensitive and ciprofloxacin-resistant patients. RESULTS:A total of 743 men underwent initial RCx. Initial RCx detected ciprofloxacin resistance in 22% of patients. A history of diabetes (p = 0.01), > 2 prior prostate biopsies (p = 0.01), and ciprofloxacin use (p = 0.002) were significant risk factors for ciprofloxacin resistance on initial RCx. The rate of new ciprofloxacin resistance following biopsy with standard ciprofloxacin prophylaxis on 1st and 2nd exposure was 17.2% and 9.1% respectively. The number of biopsy cores, interval antibiotic exposure and interval procedures performed between first and second RCx were not significant predictors of developing ciprofloxacin resistance. Patients who received a non-ciprofloxacin antibiotic between first and second RCx did not develop ciprofloxacin resistance. Antibiotic resistance profile did not significantly affect the rate or type of complications after various prostate procedures. CONCLUSIONS:Serial exposure to standard antibiotic prophylaxis for PBx and associated procedures can lead to development of ciprofloxacin resistance after each subsequent exposure. This carries important implications for serial biopsy and highlights the role for RCx prior to repeat biopsy.

BACKGROUND:Prostate cancer treatment-related regret (TRR) incorporates the myriad effects of diagnosis and treatment with associated behavioral, emotional, and interpersonal changes within the context of patient values and expectations. We aimed to investigate TRR following primary partial gland cryoablation (PPGCA). METHODS:Men with prostate cancer undergoing PPGCA since 3/2017 enrolled in a prospective outcome registry. Between June and August 2022, a validated prostate cancer related TRR decision scale was distributed. TRR score ≥40 was considered significant TRR. Men were considered potent if they reported ability to have penetration at least half the time sexual intercourse was initiated. Associations between significant TRR and baseline characteristics and longitudinal outcomes were assessed using logistic regressions. RESULTS:Of 245 men who met inclusion criteria, 163 (67%) completed the survey with median time since cryoablation 2.3 years (IQR: 1.3, 3.6). Overall, the mean composite TRR score was 12.4/100. Significant TRR was expressed by 14% of men. Among those who were potent/had erectile function at baseline, loss of potency and erectile function were associated with higher probability of significant TRR, respectively. No associations were identified between TRR and recurrence of clinically significant prostate cancer or salvage treatment. CONCLUSIONS:The overwhelming majority of men do not express TRR following PPGCA. The loss of potency or development of erectile dysfunction predisposes to TRR. It is imperative to elucidate short-, intermediate- and long-term functional and oncological outcomes in order to define factors associated with TRR to improve counseling and reduce patient regret.

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:Three-dimensional (3D) printed anatomic models can facilitate presurgical planning by providing surgeons with detailed knowledge of the exact location of pertinent anatomical structures. Although 3D printed anatomic models have been shown to be useful for pre-operative planning, few studies have demonstrated how these models can influence quantitative surgical metrics. OBJECTIVE:To prospectively assess whether patient-specific 3D printed prostate cancer models can improve quantitative surgical metrics in patients undergoing robotic-assisted radical prostatectomy (RARP). METHODS:Patients with MRI-visible prostate cancer (PI-RADS V2 ≥ 3) scheduled to undergo RARP were prospectively enrolled in our IRB approved study (n = 82). Quantitative surgical metrics included the rate of positive surgical margins (PSMs), operative times, and blood loss. A qualitative Likert scale survey to assess understanding of anatomy and confidence regarding surgical approach was also implemented. RESULTS:The rate of PSMs was lower for the 3D printed model group (8.11%) compared to that with imaging only (28.6%), p = 0.128. The 3D printed model group had a 9-min reduction in operating time (213 ± 42 min vs. 222 ± 47 min) and a 5 mL reduction in average blood loss (227 ± 148 mL vs. 232 ± 114 mL). Surgeon anatomical understanding and confidence improved after reviewing the 3D printed models (3.60 ± 0.74 to 4.20 ± 0.56, p = 0.62 and 3.86 ± 0.53 to 4.20 ± 0.56, p = 0.22). CONCLUSIONS:3D printed prostate cancer models can positively impact quantitative patient outcomes such as PSMs, operative times, and blood loss in patients undergoing RARP.

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.