Faculty Bibliography

OBJECTIVE:To characterize the oncologic outcomes five years following focal laser ablation (FLA) of localized prostate cancer. METHODS:36 men underwent in-bore FLA of prostate cancer at our institution between 2013 and 2015. Follow up included digital rectal examination and PSA testing, multiparametric MRI, and MR-guided biopsies. The primary outcome of interest was failure-free survival (FFS), defined as avoidance of salvage whole gland treatment, systemic therapy, metastasis, or death from prostate cancer. RESULTS:Of the 36 men enrolled, six were ultimately lost to follow-up. Of the remaining 30, 25 (83%) have remained free from failure over a median follow-up of 71 months. Among these patients, 10 (40%) developed in-field recurrence, with nine undergoing salvage PGA with FLA, cryotherapy, or HIFU. Five patients underwent salvage whole gland or systemic treatment and were thus considered to have failed treatment. Two patients developed metastatic disease, and after receiving radiation and ADT, both currently have undetectable PSA levels. No patients in the cohort died from prostate cancer. Limitations include a small study cohort and lack of standardized surveillance protocols two years after treatment. CONCLUSIONS:FLA for select cases of prostate cancer provides high rates of FFS, defined as freedom from whole gland or systemic treatment, metastasis, or death from prostate cancer. However, in- or out-of-field recurrence is common and often necessitates salvage ablation.

PURPOSE/OBJECTIVE:To determine whether multi-parametric magnetic resonance imaging (mpMRI) can reliably predict proximity of prostate cancer to the prostatic urethra in a contemporary series of men undergoing radical prostatectomy (RP) at two academic centers. METHODS:Clinical characteristics of consecutive men undergoing pre-operative mpMRI prior to RP and whole-mount axial serial step-sectioned pathology examination at two academic centers between Jun 2016 and Oct 2018 were analyzed retrospectively. Every tumor was characterized by its pathologic minimum distance to the prostatic urethral lumen (pMDUL). Only the cancer closest to the urethra represented the prostatic urethral index lesion. The radiologic minimum distance of the index lesion to the prostatic urethral lumen was measured and noted as ≤ 5 mm versus  > 5 mm. The sensitivity, specificity, positive and negative predicting values (PPV and NPV) and area under the receivers operating characteristics curve (AUC) were calculated for performance of mpMRI for predicting pMDUL ≤ 5 mm. RESULTS:Of the 163 surgical specimens examined, 112 (69%) exhibited a pMDUL ≤ 5 mm. These men had significantly higher grade group (GG) and advanced pathological and clinical stage. The rates of high PI-RADS score and presence of gross extracapsular extension were also significantly greater for the group with pMDUL ≤ 5 mm. The AUC, sensitivity, specificity, PPV, and NPV were 0.641, 51.8, 76.5, 82.9, and 42.4%, respectively, for mpMRI to predict pMDUL < 5 mm. CONCLUSIONS:Nearly 70% of men undergoing RP present with tumor within 5 mm of the prostatic urethra. These tumors present higher risk characteristics, and mpMRI exhibited moderate performance and high PPV in their pre-operative detection. Physicians performing partial gland ablation should take these results into consideration during treatment selection and planning.

BACKGROUND:In 2012, the United States Preventative Services Task Force (USPSTF) formally recommended against all Prostate Specific Antigen (PSA) screening for prostate cancer. Our goal was to characterize PSA screening trends in the Veterans Health Administration (VA) before and after the USPSTF recommendation, and to determine if PSA screening was more likely to be ordered based on a Veteran's race or age. METHODS:Using the VA Corporate Data Warehouse, we created 10 annual groups of PSA-eligible men covering 2009-2018. We identified all PSA tests performed in the VA to determine yearly rates of PSA screening. All statistical tests were two-sided. RESULTS:The overall rate of PSA testing in the VA decreased from 63.3% in 2009 to 51.2% in 2018 (p<.001). PSA screening rates varied markedly by age group during our study period, with men aged 70-80 having the highest initial rate and greatest decline (70.6% in 2009 to 48.4% in 2018, p<.001). Men aged 55-69 saw a smaller decline (65.2% in 2009 to 58.9% in 2018, p<.001) while the youngest men, aged 40-54, had an increase in PSA screening (26.2% in 2009 to 37.8 in 2018, p<.001). CONCLUSIONS:In this analysis of PSA screening rates among veterans before and after the 2012 USPSTF recommendation against screening, we found that overall PSA screening decreased only modestly, continuing for more than half of the men in our study. Veterans of different races had similar screening rates, suggesting that VA care may minimize racial disparities. Veterans of varying age experienced significantly different trends in PSA screening.

BACKGROUND:Several consensus statements recommend serial serum prostate-specific antigen (PSA), multi parametric magnetic resonance imaging (mpMRI), and prostate biopsy following partial gland ablation. We determined the rate of persistent in-field disease following primary partial gland cryo-ablation and whether PSA or mpMRI are reliable predictors of in-field disease persistence. METHODS:Between March 2017 and July 2019, subjects meeting eligibility criteria for partial gland cryoablation were enrolled into an IRB approved outcomes registry. PSA, mpMRI, and prostate biopsy (four cores targeting the ablation zone + six ipsilateral systematic cores) were performed per protocol 6 months following intervention. Binary logistic regression was employed to calculate odds ratio (OR) of PSA decrease, and suspicious mpMRI effect on cancer persistence. The performance of mpMRI for predicting in-field persistence of PCa was evaluated by area under the receiver operation characteristics curve (AUC). RESULTS:Of the 83 eligible men undergoing partial gland cryoablation, 70 (84.3%) underwent 6-month protocol prostate biopsy. Five (7.1%) biopsies exhibited any in-field disease persistence. Only one (1.4%) of these cancers was Gleason grade > 1. Neither PSA decrease or suspicious mpMRI reliably predicted cancer persistence, with OR of 1.6 (0.25-8.6) and 1.5 (0.02-1.3), respectively. AUC of mpMRI for predicting in-field disease persistence was 0.554. CONCLUSIONS:In this cohort of patients undergoing partial gland cryo-ablation, the incidence of persistent disease was low. PSA and mpMRI were not reliable predictors of in-field disease persistence. Based on these data, consideration may be given to deferring early follow-up biopsy in appropriate patients.

PURPOSE/OBJECTIVE:To demonstrate the generalizability of PRECISION findings and apply the PRECISION biopsy strategy to a contemporary cohort to characterize cancers missed by employing this strategy. MATERIALS AND METHODS/METHODS:629 men biopsied between 2/2015-9/2018 met PRECISION inclusion criteria. Men with PI-RADS 1-2 MRI were only biopsied if high clinical suspicion for cancer. Missed cancers were defined as prostate cancer (PCa) identified uniquely on systematic biopsy (SB) in men with PI-RADS 3-5 MRI, or on either SB or MRI-targeted prostate biopsy (MRI-TB) in men with PI-RADS 1-2 MRI. Outcomes included 1) clinically-significant PCa (csPCa), ≥Gleason grade group (GG) 2, detection rate (CDR), 2) missed csPCa rate upon application of PRECISION biopsy strategy, 3) GG distribution, core size, spatial orientation, and oncologic risk among missed cancers. RESULTS:Application of the PRECISION biopsy strategy to the study cohort resulted in avoidance of biopsy in 28%, similar MRI-TB CDR to PRECISION, reduction of GG1 CDR by 60%, and reduction of csPCa CDR by 19%. Missed csPCa were often <6 mm (54.5%), GG2 (67.3%), and low-risk by clinical nomogram (74.6%). GG1 cancers identified uniquely on SB were often contralateral to MRI target (46.4%), while missed csPCa was predominantly ipsilateral (81%). Limitations include biopsy of only men with high-risk clinical features among PIRADS 1-2 MRI, potentially overestimating the csPCa CDR. CONCLUSIONS:The study cohort demonstrated generalizability of PRECISION findings. Applying the PRECISION biopsy strategy greatly reduces GG1 CDR, while missing a small number of csPCa, typically small volume, low-risk, and GG2. Missed csPCa are predominantly ipsilateral to MRI target, possibly representing targeting error.

Historically, the primary objection to partial gland ablation (PGA) for management of prostate cancer (CaP) has been disease multifocality and inability to localize significant disease. Improved disease localization and risk stratification with multiparametric magnetic resonance imaging and targeted biopsy, along with its minimal adverse impact on quality of life has enabled PGA to gain acceptance. Today, the primary barrier for adopting PGA is its unknown oncological outcomes. Objectives of this review are to provide a rationale for PGA for managing intermediate-risk (IR) CaP; review oncological outcomes following PGA for IR disease; and assess whether there is adequate data to justify PGA for management of IR CaP. There is no consensus how to assess or define oncological outcomes following PGA. We propose the following definitions for oncological outcomes: Oncological control (detection of any cancer following biopsy), oncological failure (detection of Gleason grade group >1 on follow-up biopsy), and oncological treatment failure (any disease that precipitate salvage treatment). There are only 3 reports in the literature where inclusion criteria specified pretreatment targeted biopsy and reflex prostate biopsy within 1 year of PGA in cohorts of men where >50% had Gleason grade group >1 disease. These studies reported that prostate-specific antigen is not a reliable surrogate and multiparametric magnetic resonance imaging is reliable when prevalence of in-field CaP is high. "Freedom from failure" is used to assess longer-term oncologic outcomes, and is defined by freedom from CaP mortality, androgen deprivation therapy, or whole-gland treatment. Rationale for PGA in selected cases of IR CaP is compelling and early oncological studies are reassuring. If patient selection is done judiciously, oncologic outcomes are disclosed, and follow-up plan is rigorously implemented, it is unlikely rates of metastasis or CaP mortality with be adversely impacted and many men will avoid or defer adverse effects of whole-gland treatment.

OBJECTIVES/OBJECTIVE:To compare both the concordance between the 4Kscore® and SelectMDx® for informing decision to perform prostate biopsy (PB) and the performance of these tests for detecting clinically significant prostate cancer (csPCa). Several biomarkers were developed to inform decisions whether to perform a PB based on the probability of detecting csPCa. There is a paucity of studies directly comparing them METHODS: Between 11/2018 and 4/2019, all new referrals with the diagnosis of elevated PSA were advised to undergo 4Kscore® and SelectMDx® in order to guide the selection of candidates for PB. Men were advised to undergo PB if the reported biomarker risk for detecting csPCA was ≥7.5%, or if they presented a PI-RADS ≥1 MRI. Cohen's Kappa was used to assess the concordance between the binary 4Kscore® and SelectMDx® results using externally validated cutoffs of 7.5% and 12%. Receiver operating characteristics curve and area under the curve (AUC) assessed the performance of each biomarker for predicting csPCa. RESULTS:Of 128 consecutive patients referred, 114 (89.1%) underwent 4Kscore® and SelectMDx®, The kappa coefficient between the biomarkers using the 7.5% cutoff was 0.184 (poor concordance) and 0.22 using the 12% cutoff. The two biomarkers yielded discordant guidance whether to proceed with PB in 46% and 38% of cases, respectively. csPCa was found in 22 of the 50 patients who underwent PB (44%). The AUC for 4Kscore® and SelectMDx® was 0.830 (95%CI: 0.710 - 0.949) and 0.672 (95%CI: 0.517 - 0.828) (p=0.036), respectively. CONCLUSION/CONCLUSIONS:The discordance observed between the 4Kscore® and SelectMDx® is disconcerting. The 4Kscore® when combined with MRI was superior to the SelectMDx® for detecting csPCa. Prospective comparative studies must be performed to optimize implementation of biomarkers for selecting candidates for PB.

Current guidelines recommend conservative management as the preferred option for most low-risk prostate cancer cases, with certain possible exceptions (age <55yr, African Americans, and high-volume grade group 1). Although previous studies have documented substantial heterogeneity in the uptake of conservative management, less is known about the underlying reason for this variation and whether it is due to guideline-concordant factors (age, race, and biopsy cancer volume). We explored variation in the use of conservative management for low-risk prostate cancer among 20 597 men diagnosed in the US Veterans Affairs health care system from 2010 to 2016. Conservative management increased substantially over this time from 51% to 76% (p< 0.001). However, there was substantial variation by facility (35-100%). Multivariable analysis revealed that patient factors included in the guidelines (e.g., age and biopsy cores), other patient factors (eg, marital status and PSA) and non-patient factors (eg, geographic region, case volume, year) were associated with conservative management use. In conclusion, even within an integrated health care system, there remains significant heterogeneity in the uptake of conservative management for low-risk prostate cancer. Both guideline-concordant factors and other factors not discussed in the guidelines were associated with conservative management use. PATIENT SUMMARY: In the US Veterans Affairs health care system the vast majority of men with low-risk prostate cancer were managed conservatively by 2016, although there was significant variation by facility. Patient factors specifically mentioned in guidelines had the greatest impact on prediction of conservative management.