Faculty Bibliography

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.

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.

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.

OBJECTIVE:To assess 5-year oncologic outcomes following primary partial gland cryo-ablation (PPGCA) in intermediate risk prostate cancer. METHODS:Of 476 men undergoing PPGCA enrolled in our prospective oncologic and functional outcomes study, 313 had MRI concordant intermediate risk prostate cancer with no out-of-field Gleason Grade Group (GGG) ≥2, gross extracapsular extension or extreme apical disease on pre-treatment mpMRI. PSA was monitored every 6 months, and mpMRI at 6-12, 24, 42 and 60 months. Protocol biopsy at 6-12 months and 24 months were discontinued after interim analysis showing low rates of clinically-significant prostate cancer (csPCa) defined as any GGG≥2 disease. Freedom-from-failure (FFF) was defined as no prostate cancer specific mortality, metastatic disease, or whole-gland salvage treatment (WGST) RESULTS: csPCa was detected in 33 (10.5%) subjects. 91 had ≥4.5 years of follow-up data with a mean of 8.9, 3.4, and 2.0 surveillance PSA tests, MRIs, and prostate biopsies; none were lost to follow-up. At 5-years, rates of freedom-from-recurrence of in-field, out-of-field and overall csPCa were 86% (95% CI: 78-96), 85% (95% CI: 63-94), and 70% (95% CI: 57-84). The proportion with freedom-from-failure (FFF) at 5 years was 89% (95% CI: 83-95). None died from prostate cancer, 1 (1%) developed metastasis, 15 (16.5%) underwent WGST, and 15 (16.5%) underwent salvage focal therapy (FT). Only 3 of 91 (3.3%) eligible men were noncompliant with 5-year surveillance protocol. CONCLUSION/CONCLUSIONS:Very encouraging intermediate-term oncological outcomes following PPGCA were observed with very high compliance to a rigorous prospective protocol for identifying recurrent csPCa.

OBJECTIVE:To evaluate predictors of contralateral clinically significant prostate cancer (csPCa) in men with biopsy-proven unilateral lesions on magnetic resonance imaging (MRI). METHODS:We retrospectively identified men with no prior diagnosis of PCa with unilateral biopsy-confirmed csPCa within PI-RADS 2-5 lesions within our institutional biopsy database. Multivariate logistic regression was used to identify clinical predictors of contralateral disease. RESULTS:Four hundred ninety men met study inclusion criteria, of which 385 men (78.6%) had no contralateral csPCa and 105 men (21.4%) had contralateral csPCa (Fig. 1). Prior negative biopsy (OR 0.34 [0.14, 0.75], P = .012), prostate-specific antigen density (OR 18.8 [2.77, 249], P = .017), and tumor location in the transverse plane ("Posterior": OR 1.93 [1.02, 3.87], P = .048; "Throughout Transverse Plane": OR 6.56 [2.26, 19.6], P < .001) were significantly associated with contralateral csPCa in multivariate logistic regression models. However, there appear to be no attributes within the MRI-targeted tumor that reliably predict contralateral csPCa (Table 2). CONCLUSION/CONCLUSIONS:Approximately 20% of men with unilateral MRI findings and csPCa on targeted biopsy were found to have contralateral csPCa on systematic biopsy (SB). Prior negative biopsy was associated with a decreased odds of contralateral csPCa. Prostate-specific antigen density and tumor in the posterior aspect of or throughout the transverse plane were associated with increased odds of contralateral csPCA. Consideration of these clinical factors may afford an opportunity to only use SB in cases in which the odds of contralateral csPCa are high.

INTRODUCTION/BACKGROUND:Local disease recurrence following focal therapy (FT) for prostate cancer may be due to failure to eradicate focal disease or development of disease in the untreated prostate (in- and out-of-field recurrences). Several studies suggest in-field contrast enhancement (CE) on post-treatment multi-parametric (mp) MRI between 6-12 months following FT indicates residual disease. The present study assesses the incidence and oncologic implications of early CE observed following primary partial gland cryoablation (PPGCA). MATERIAL AND METHODS/METHODS:The surveillance protocol for men enrolled in our prospective outcomes study following PPGCA included mpMRI at 6-12 months, 2 years, 3.5 years, and 5 years. All cases of in-field early CE were re-reviewed retrospectively and graded using the previously described Prostate Imaging after Focal Ablation scoring system. All patients exhibiting early CE were re-evaluated by a single radiologist at 2-year mpMRI Results: A total of 320 men enrolled in our PPGCA outcomes study had at least 6 months of follow up. Three hundred fifteen (98%) of these men had undergone post-PPGCA mpMRI at 6-12 months. Of these men, 9 were found to have early in-field CE and 8 underwent repeat MRI at 2 years. In all 8 cases, the CE resolved on the 2-year mpMRI. Of these 8 patients, seven underwent repeat protocol biopsy at 2 years and in-field significant disease was detected in only 1 case. CONCLUSIONS:The most compelling evidence that early CE is not indicative of prostate cancer recurrence is that all lesions resolved within 24 months. While incidence of early CE is low, its consistent resolution calls into question the clinical significance of this finding after PPGCA.

OBJECTIVES/OBJECTIVE:To evaluate the interaction of patient age and Prostate Imaging-Reporting and Data System (PI-RADS) score in determining the grade of prostate cancer (PCa) identified on magnetic resonance imaging (MRI)-targeted biopsy in older men. PATIENTS AND METHODS/METHODS:From a prospectively accrued Institutional Review Board-approved comparative study of MRI-targeted and systematic biopsy between June 2012 and December 2022, men with at least one PI-RADS ≥3 lesion on pre-biopsy MRI and no prior history of PCa were selected. Ordinal and binomial logistic regression analyses were performed. RESULTS:A total of 2677 men met study criteria. The highest PI-RADS score was 3 in 1220 men (46%), 4 in 950 men (36%), and 5 in 507 men (19%). The median (interquartile range [IQR]) patient age was 66.7 (60.8-71.8) years, median (IQR) prostate-specific antigen (PSA) level was 6.1 (4.6-9.0) ng/mL, median (IQR) prostate volume was 48 (34-68) mL, and median (IQR) PSA density was 0.13 (0.08-0.20) ng/mL/mL. Clinically significant (cs)PCa and high-risk PCa were identified on targeted biopsy in 1264 (47%) and 321 (12%) men, respectively. Prevalence of csPCa and high-risk PCa were significantly higher in the older age groups. On multivariable analyses, patient age was significantly associated with csPCa but not high-risk PCa; PI-RADS score and the interaction of age and PI-RADS score were significantly associated with high-risk PCa but not csPCa. CONCLUSION/CONCLUSIONS:In our cohort, the substantial rate of high-risk PCa on MRI-ultrasound fusion targeted biopsies in older men, and its significant association with MRI findings, supports the value of pre-biopsy MRI to localise disease that could cause cancer mortality even in older men.

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.