Faculty Bibliography

PURPOSE/UNASSIGNED:Recent publications have renewed interest in prophylactic pelvic radiation therapy for higher-risk prostate cancer, as well as dose escalation for magnetic resonance imaging (MRI)-defined intraprostatic lesions. Here, we explore the use of pelvic nodal irradiation with a 3-fraction stereotactic body radiation therapy (SBRT) boost to the prostate and seminal vesicles, with a simultaneous MRI-directed focal intraprostatic lesion-ablative microboost (MIB). METHODS AND MATERIALS/UNASSIGNED:We evaluated an institutional registry of patients undergoing pelvic nodal radiation followed by an SBRT boost to the prostate and seminal vesicles from April 2021 to March 2023. The study was approved by the local institutional review board (study #00001269). All patients were treated with pelvic nodal irradiation followed by a 3-fraction SBRT boost. The prostate SBRT boost dose was primarily 2100 cGy in 3 fractions (an accommodated range of 1800-2100 cGy). A subgroup of 15 patients received an MIB to an additional dose of 2300 cGy in 3 fractions (range, 2100-2400 cGy). The distribution of adverse event grades for acute and late gastrointestinal (GI) and genitourinary (GU) toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. RESULTS/UNASSIGNED:Fifty-eight patients underwent pelvic nodal irradiation followed by an SBRT boost to the prostate, with the distribution of risk groups as follows: patients were either in the high (36.2%, n = 21) or very high (34.5% n = 20) risk groups, whereas those with known nodal disease (19.0%, n = 11) or intermediate risk (10.3%, n = 6) comprised the rest of the study population. Most patients received androgen-deprivation therapy. The prostate SBRT boost dose was primarily 2100 cGy in 3 fractions. Fifteen patients received an MIB to an additional dose of 2300 cGy in 3 fractions. A median follow-up of 8.7 months was used to document the incidence of GU and GI toxicity. The distribution of GI and GU toxicity showed no significant difference between the MIB and non-MIB subcohorts at either the acute (<90 days) or late (>90 days) time points. Two grade 3 toxicities were observed, both in the non-MIB cohort. Grade 2+ GI and GU toxicities were not significantly different between the 2 groups, as assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. CONCLUSIONS/UNASSIGNED:In the early follow-up period, we observed no significant difference in GI or GU toxicity between those who underwent MIB and those who did not. These results suggest that MRI-directed SBRT MIB did not increase GI toxicity and may even reduce GU toxicity compared with standard treatment. Future research should explore long-term side effects, with attention to the Expanded Prostate Cancer Index Composite (EPIC) scores and oncologic outcomes of this novel method of dose escalation.

OBJECTIVE:Indeterminate lesions on prostate-specific membrane antigen (PSMA)-PET are challenging to address. We aimed to develop, implement, and evaluate a multidisciplinary consensus algorithm that integrates existing interpretation systems with multimodality imaging and clinicopathological information for interpreting indeterminate bone and lymph node lesions on PSMA-PET. MATERIALS AND METHODS/METHODS:This was a retrospective single-center study on a prospectively implemented algorithm. We included all consecutive prostate cancer patients whose PSMA-PET findings for indeterminate bone lesions or lymph nodes were discussed at a multidisciplinary tumor board (MDT) in 2024-2025. An algorithm determining the level of suspicion for metastasis was developed in a multidisciplinary fashion, incorporating lesion location, conventional imaging features, PSMA-PET characteristics, and clinicopathological information. The application of the algorithm and outcomes were documented, compared against a composite reference standard. Comparisons were made with PSMA-RADS and PROMISE V2 PSMA-expression scores. RESULTS:81 patients (median age 68, interquartile range 64-75) were included. Algorithm results were benign (48.1% [39/81]), equivocal (4.9% [4/81]), metastasis (40.7% [33/81]), and mixed (benign and metastatic lesions, 6.2% [5/81]). The algorithm was correct in 94.1% (64 of 68 patients with a sufficient reference standard). The algorithm was discordant with PSMA-RADS in 54.3% (44/81) and with PROMISE V2 PSMA-expression score in 71.6% (58/81). The frequency of equivocal lesions was lower using the algorithm (4.9% [4/81]) compared with PSMA-RADS (53.1% [43/81]) and PSMA-expression score (64.2% [52/81]). CONCLUSION/CONCLUSIONS:A multidisciplinary consensus algorithm for interpreting indeterminate bone lesions and lymph nodes on PSMA-PET was developed and implemented. Integrating clinicopathological information and multimodality imaging in an MDT setting reduced equivocal interpretations. KEY POINTS/CONCLUSIONS:Question While prostate-specific membrane antigen (PSMA)-PET has become essential in the management of prostate cancer, indeterminate bone lesions and lymph nodes remain challenging to address. Findings A multidisciplinary algorithm for interpreting indeterminate bone lesions and lymph nodes on PSMA-PET, incorporating clinicopathological information and multimodality imaging, reduced the frequency of equivocal interpretations. Clinical relevance An algorithm for interpreting indeterminate bone lesions and lymph nodes on PSMA-PET, incorporating clinicopathological information and multimodality imaging in a multidisciplinary tumor board setting, decreases the frequency of equivocal interpretations and can potentially help management decisions.

OBJECTIVES/UNASSIGNED:To determine the performance of MRI for detecting clinically significant prostate cancer (csPCa) recurrence following focal cryo-ablation over five years of oncological surveillance. SUBJECTS AND METHODS/UNASSIGNED:A total of 305 men with intermediate-risk prostate cancer undergoing focal cryo-ablation (FCA) at our referral centre between 03/2017 and 03/2024 were prospectively enrolled in an outcomes registry. Selection criteria, treatment planning and oncological surveillance were standardized. The initial surveillance protocol included MRI at six months, two, 3.5, five years, and surveillance prostate biopsy at six months, two and five years. The surveillance protocol biopsy at six months and two years was abandoned for a negative MRI in May 2019 and November 2020. Performance statistics of MRI for detecting csPCa recurrence were assessed among mandatory MRI and biopsy dyads at six months and two years. Clinically significant prostate cancer detection rates for suspicious (positive) and negative MRI included all subjects. RESULTS/UNASSIGNED:Sensitivity, specificity, positive predictive value and negative predictive value of MRI to predict csPCa is 25%, 93%, 29% and 91%. The csPCa detection rate for positive and negative MRI was 40% and 7.0%, respectively. The area under the receiver operating characteristic curve for MRI as a predictor of csPCa was 0.60, suggesting limitations of MRI for predicting csPCa. A limitation is that a validated instrument for positive MRI was not available during the study. CONCLUSIONS/UNASSIGNED:Six-month MRI is not recommended owing to its very low csPCa detection rate. The increasing csPCa detection rates at two and five years suggest these are reasonable time points to perform MRI. Prostate biopsy should be performed on all cases with positive MRI, and can safely be deferred in most cases with negative MRI.

OBJECTIVES/OBJECTIVE:To compare the clinically significant prostate cancer detection rate (csPCaDR) and pathological characteristics of magnetic resonance imaging (MRI) visible (MRIv) and MRI invisible (MRIi) cancers among men undergoing surveillance after ablative focal therapy (AFT) for intermediate-risk PCa. PATIENTS AND METHODS/METHODS:A total of 305 five men enrolled in an Institutional Review Board-approved primary partial gland cryoablation (PPGCA) outcomes registry meeting the following inclusion criteria: an MRI region of interest (ROI) Prostate Imaging-Reporting and Data System 2-5 concordant with unilateral intermediate-risk disease (Gleason Grade Group [GGG] 2 or 3 disease), no gross extraprostatic extension on MRI, no GGG ≥2 contralateral to the ROI, and at least 6 months of follow-up. Protocol MRI was performed at 6, 24, 42 and 60 months. Biopsy indications evolved over time. Any Gleason pattern 4 (GP4) represented a clinically significant PCa recurrence (csPCaR). Pathological disease characteristics, csPCaDR, and salvage treatments were compared for MRIv and MRIi disease. Baseline and post-treatment characteristics were compared between MRIv and MRIi csPCaR. Ordinal and binary measures were compared with Mann-Whitney rank-sum test. Categorical testing for differences was performed with chi-square testing. RESULTS:Of 665 post-treatment MRIs, 87 (13.1%) and 578 (86.9%) were positive (+ve) and negative (-ve) for csPCaR, respectively. Biopsies were taken in 62 of the 87 +ve MRIs and 179 of the 578 -ve MRIs, with a csPCaDR of 43.5% and 10.6% for +ve and -ve MRI, respectively. Of the 46 csPCaRs, 28 (61%) and 18 (39%) were associated with +ve and -ve MRI, respectively. The median linear length of GP4 for MRIv and MRIi csPCaR was 2.6 and 0.6 mm, respectively (P = 0.08). Four (14%) and eight (44%) MRIv and MRIi csPCaRs were managed with continued active surveillance (P = 0.03). CONCLUSION/CONCLUSIONS:The cost and morbidity of surveillance following PPGCA can be safely reduced by avoiding biopsy in most cases with -ve MRI.

INTRODUCTION/BACKGROUND:High-volume (≥ 50 %) biopsy core involvement (HVCI) is an independent risk factor for unfavorable intermediate-risk prostate cancer by NCCN guidelines. The studies demonstrating increased recurrence in high-volume disease were conducted in an era of conventional fractionation, often without dose-escalation. In the SBRT era, we explore the value of this pathologic criteria in intermediate-risk disease. METHODS:A large institutional database was reviewed to identify patients diagnosed with localized intermediate-risk (Gleason Grade [GG] 2 and 3) disease, who were treated with definitive five-fraction SBRT without ADT. HVCI was analyzed (1) traditionally with all positive cores given equal weight as well as weighted with a positive core of GG1 to GG3 given (2) linearly and (3) exponentially increased weight. Oncologic outcomes were analyzed using Cox and linear regression analysis. RESULTS:From 2009 to 2018, 888 patients with intermediate-risk prostate cancer were treated with five-fraction SBRT monotherapy to a median dose of 3500 cGy. The majority (68 %) had GG2 disease. HVCI was present in the 22 % and was inversely related to prostate volume and directly related to T-stage. Biochemical disease-free survival (BDFS) was not significantly associated with HVCI in the cohort (p = 0.47) nor in the GG2 (p = 0.85) and GG3 (p = 0.26) sub-cohorts. Similarly, when linear or exponential weight was given to a core with higher-grade disease, there was no association with BDFS. Finally, PSA nadir was not associated with HVCI; however, time to PSA nadir (TTN) was negatively associated with HVCI in the GG3 sub-cohort (p = 0.04). CONCLUSION/CONCLUSIONS:With a median follow-up of 4.1 years, HVCI was not associated with BDFS following SBRT monotherapy, particularly in patients with otherwise favorable intermediate-risk disease (GG2). TTN analysis suggests that HVCI may remain prognostic in GG3 disease (by definition unfavorable intermediate-risk). Further work should prospectively confirm whether HVCI is unnecessary in risk-stratifying GG2 disease in the SBRT era.

OBJECTIVES/OBJECTIVE:To determine the incidence of isolated high grade prostatic epithelial neoplasia (iHGPIN) following magnetic resonance imaging (MRI)-ultrasonography co-registration fusion targeted biopsy (MRFTB) coupled with systematic biopsy (SB) and to assess the detection rates of clinically significant prostate cancer (csPCa). PATIENTS AND METHODS/METHODS:Beginning in June 2012, most patients at our institution underwent multiparametric MRI (mpMRI) before prostate biopsy. Biopsies were performed between June 2012 and October 2021. The surveillance protocol for iHGPIN included prostate-specific antigen assessment every 6 months, digital rectal examinations annually, and multiparametric MRI (mpMRI) at 3 years. Repeat biopsies were recommended primarily for suspicious mpMRI, defined as a new Prostate Imaging-Reporting and Data System (PI-RADS) score >2 region of interest (ROI) or an increase in size of the pre-existing ROI. RESULTS:Of the 628 biopsies, 230 (33.7%), 48 (7.0%), 404 (59.2%) were interpreted as benign, iHGPIN, or prostate cancer (PCa), respectively. Of these cancers 140 (34.7%) and 264 (65.3%) were low-risk PCa and csPCa, respectively. iHGPIN was detected in MRRFTB only, SB only, and both MRFRB + SB in six (12.5%) 36 (75%), and six patients (12.5%), respectively. Of the 32 MRI scans performed at 3 years, a new PI-RADS score >2 ROI or an increase in the size or PI-RADS score of a pre-existing ROI was observed in four and eight patients, respectively. Nine of these underwent biopsy. Three additional biopsies were performed on non-suspicious mpMRI. csPCa was detected in two patients, both with an enlarging ROI. CONCLUSION/CONCLUSIONS:To our knowledge, this is the first study examining the incidence, natural history, and subsequent csPCa detection rates for iHGPIN in the era of mpMRI and MRI targeted biopsy. The lower prevalence of iHGPIN is attributed to the selection of biopsy candidates based on mpMRI and an increased likelihood of detecting pre-existing csPCa. Our findings provide compelling evidence that biopsy strategies limited to MRI targets will almost eliminate iHGPIN detection while decreasing detection of csPCa. A 3-year biopsy should be performed only in men with suspicious mpMRI.

BACKGROUND:There is increasing interest in ablative focal therapy (AFT) for treating clinically localized prostate cancer. The objective of the present study is to report treatment related complications and regret, functional and oncological outcomes of primary partial gland cryo-ablation (PPGCA) for men with low-risk prostate cancer associated with a multiparametric Magnetic Resonance Imaging (mpMRI) target. METHODS:The present analysis includes 54 subjects enrolled in an Institutional Review Board (IRB) approved outcomes registry with low-risk prostate cancer undergoing PPGCA whose disease was associated with an MRI target. The surveillance protocol included mpMRI at 6 months, 2, 3.5, and 5 years, and surveillance prostate biopsies. Clinically significant prostate cancer (csPCa) recurrence was defined as any biopsy core with Gleason pattern (GP4). Freedom-from-failure (FFF) included men who: did not experience prostate cancer mortality, develop metastasis or undergo whole gland salvage treatment (WGST). All men underwent at least 1 post-treatment biopsy. The International Prostate Symptom Score (IPSS), Sexual Health Inventory for Men (SHIM) and Treatment Related Regret (TRR) surveys were self-administered at 1 year. RESULTS:There were no day-of-surgery or 30-day postoperative hospital admissions. There were no rectal injuries or other technical complications. The 5-year freedom from csPCa recurrence and FFF was 84% and 96%, respectively. At 1 year, only 1 man used a protective pad and no men expressed significant TRR. Overall, the mean decreases in IPSS and SHIM scores between baseline and 1-year was 3.4 (34.7%) and 3.7 (20.4%), respectively. Erectile function was preserved in 72% of men by 1 year. CONCLUSION/CONCLUSIONS:The favorable oncological outcomes, absence of treatment related complications, Treatment Related Regret (TRR), urinary incontinence, rectal injury, improvement in lower urinary tract symptoms (LUTS), and modest changes in sexual function suggests PPGCA should be considered an option for managing selected cases of low-risk prostate cancer associated with an MRI target.