Favorable Intermediate Risk Research Articles

Intensity modulated radiation therapy with stereotactic body radiation therapy boost for unfavorable prostate cancer: five-year outcomes

PurposeIntensity-modulated radiation therapy (IMRT) with brachytherapy boost for unfavorable prostate cancer has been shown to improve biochemical relapse-free survival compared to IMRT alone. Stereotactic body radiation therapy (SBRT) is a less-invasive alternative to brachytherapy. Early outcomes utilizing SBRT boost suggest low rates of high-grade toxicity with a maintained patient-reported quality of life. Here, we report the 5-year progression-free survival (PFS) and prostate cancer-specific survival (PCSS) of patients treated with IMRT plus SBRT boost.Materials and methodsBetween 2008 and 2020, 255 patients with unfavorable prostate cancer were treated with robotic SBRT (19.5 Gy in three fractions) followed by fiducial-guided IMRT (45–50.4 Gy) according to an institutional protocol. For the first year, the patient’s PSA level was monitored every 3 months, biannually for 2 years, and annually thereafter. Failure was defined as nadir + 2 ng/mL or a rising PSA with imaging suggestive of recurrence. Detection of recurrence also included digital rectal examination and imaging studies, such as MRI, CT, PET/CT, and/or bone scans. PFS and PCSS were calculated using the Kaplan–Meier method.ResultsThe median follow-up period was 71 months. According to the NCCN risk classification, 5% (13/255) of the patients had favorable intermediate-risk disease, 23% (57/255) had unfavorable intermediate-risk disease, 40% (102/255) had high-risk disease, and 32% (83/255) had very high-risk disease. Androgen deprivation therapy was administered to 80% (204/255) of the patients. Elective pelvic lymph node IMRT was performed in 28 (10%) patients. The PFS for all patients at 5 years was 81% (favorable intermediate risk, 91%; unfavorable intermediate risk, 89%; high-risk, 78%; and very-high risk, 72%). The PCSS for all patients at 5 years was 97% (favorable intermediate risk, 100%; unfavorable intermediate risk, 100%; high risk, 100%; and very high risk, 89%).ConclusionThe incidence of failure following IMRT plus SBRT for unfavorable prostate cancer remains low at 5 years.

Long-term Outcomes from a Phase 1 Dose Escalation Study Using Stereotactic Body Radiotherapy for Patients with Low- or Intermediate-risk Prostate Cancer

BackgroundUltrahypofractionated stereotactic body radiation therapy (SBRT) has become a standard treatment intervention for localized prostate cancer. ObjectiveTo report final long-term tumor control outcomes and late gastrointestinal (GI) and genitourinary (GU) toxicities from a single-center phase 1 dose escalation study using SBRT for patients with low- or intermediate-risk prostate cancer. Design, setting and participantsBetween 2009 and 2012, 136 patients were enrolled and treated. The initial dose level was 32.5 Gy in five fractions. Doses were then sequentially escalated to 35 Gy, 37.5 Gy, and 40 Gy in five fractions delivered every other day. Outcome measurements and statistical analysisThe primary endpoint was late treatment-related toxicity. Secondary endpoints included prostate-specific antigen (PSA) failure. Results and limitationsThe median follow-up was 10.5 yr for the 32.5-Gy group, 9.9 yr for the 35-Gy group, 8.2 yr for the 37.5-Gy group, and 7.3 yr for the 40-Gy group. The 8-yr cumulative incidence of PSA failure was 26% for 32.5 Gy, 15% for 35 Gy, 3.4% for 37.5 Gy, and 6.6% for 40 Gy. Higher radiation dose (37.5–40 Gy) and favorable intermediate risk (vs unfavorable intermediate risk) were associated with better PSA recurrence rates (p = 0.011 and 0.002, respectively). The 8-yr actuarial probability rates for survival free from late grade ≥2 toxicity were 94% for GI toxicity and 86% for GU toxicity. No grade 4 events were recorded. Higher dose levels were not associated with higher rates of late grade ≥2 GI (p = 0.2) or GU (p > 0.9) toxicity. ConclusionsSBRT doses ranging from 32.5 to 40 Gy were associated with low incidence of moderate or severe toxicities. Higher doses resulted in superior disease control outcomes 8 yr after treatment. Patient summaryWe investigated the association between the radiotherapy dose used and the rate of control of prostate cancer. We found that higher doses resulted in more favorable outcomes without excess toxicity.This trial is registered on ClinicalTrials.gov as NCT00911118.

Analysis of active surveillance uptake for localized prostate cancer in Quebec in 2016: A Canadian bicentric study and comparison with 2010 data

IntroductionActive surveillance (AS) has emerged as a primary management strategy for low-risk prostate cancer (PC) patients. We aimed to assess AS uptake over a 1-year snapshot throughout Quebec and to compare it to 2010 multicentric Canadian data. MethodsA retrospective chart review and data collection was performed in 1 academic and 2 non-academic community centres from Quebec, among men identified in 2016 with localized T1c-T2c PC on biopsy, fulfilling NCCN criteria of low-risk (LR)-PC, including very-low-risk (VLR) and non-VLR-PC, and favourable-intermediate risk (FIR)-PC. AS adherence was defined when chosen as initial strategy, without any radical treatment within 6 months. ResultsOverall, 259 patients fulfilled the inclusion criteria with 50.2% of VLR-PC patients. At 6 months, 81% patients in the LR group and 65% in the FIR group were considered as adherent to AS, in both centres, but with an increased use of AS in the community centres compared to 2010 data. The rates of AS maintenance decreased at 12 months to respectively 69% and 58%. Among the VLR group, the rate of initiation was 98% and decreased to 85% at 12 months. ConclusionOur data suggest that the majority of low-risk PC patients indeed initiated an AS in 2016, with even a greater proportion of VLR-PC patients compared to 2010. This ideal strategy should be encouraged and improved at 12 months, and assessed with recent data and longer follow-up. Level of evidence4

Prediction of clinically significant prostate cancer through urine metabolomic signatures: A large-scale validated study

PurposeCurrently, there are no accurate markers for predicting potentially lethal prostate cancer (PC) before biopsy. This study aimed to develop urine tests to predict clinically significant PC (sPC) in men at risk.MethodsUrine samples from 928 men, namely, 660 PC patients and 268 benign subjects, were analyzed by gas chromatography/quadrupole time-of-flight mass spectrophotometry (GC/Q-TOF MS) metabolomic profiling to construct four predictive models. Model I discriminated between PC and benign cases. Models II, III, and GS, respectively, predicted sPC in those classified as having favorable intermediate risk or higher, unfavorable intermediate risk or higher (according to the National Comprehensive Cancer Network risk groupings), and a Gleason sum (GS) of ≥ 7. Multivariable logistic regression was used to evaluate the area under the receiver operating characteristic curves (AUC).ResultsIn Models I, II, III, and GS, the best AUCs (0.94, 0.85, 0.82, and 0.80, respectively; training cohort, N = 603) involved 26, 24, 26, and 22 metabolites, respectively. The addition of five clinical risk factors (serum prostate-specific antigen, patient age, previous negative biopsy, digital rectal examination, and family history) significantly improved the AUCs of the models (0.95, 0.92, 0.92, and 0.87, respectively). At 90% sensitivity, 48%, 47%, 50%, and 36% of unnecessary biopsies could be avoided. These models were successfully validated against an independent validation cohort (N = 325). Decision curve analysis showed a significant clinical net benefit with each combined model at low threshold probabilities. Models II and III were more robust and clinically relevant than Model GS.ConclusionThis urine test, which combines urine metabolic markers and clinical factors, may be used to predict sPC and thereby inform the necessity of biopsy in men with an elevated PC risk.

Long Term Results of Prostate Cancer Patients Treated with Cs131 LDR Brachytherapy Compared with Recently Published SBRT Data.

The use of LDR prostate brachytherapy (PB) as monotherapy has been established as a definitive treatment for prostate cancer patients with low and favorable intermediate risk. Patients choose PB in part due to it being minimally invasive with a quick return to full activity. Recently, there has been more interest in using shorter courses of radiotherapy, citing the same rationale. We present patient-reported outcomes from a cohort of patients treated at our institution treated with PB using Cs131to compare our outcomes with the 5-year data from the published RTOG 0938 MATERIALS/METHODS: We analyzed data from patients treated at our institution with Cs131 PB monotherapy who completed the EPIC questionnaire at baseline and at 1, 2, and 5 years after treatment. Urinary and bowel functions were evaluated based on the EPIC questionnaire the same way they were evaluated in the recently published RTOG 0938, assessing the proportion of patients with deterioration from baseline of >5 for urinary function and >2 for bowel function. We also report the 5- and 10-year bDFS calculated using the Kaplan Meier method RESULTS: A total of 138 patients were included in this analysis with a median age of 66 and median follow-up of 121.5 months. Change in urinary score of >2 at 1, 2, and 5 years was 62%, 53%, and 43% respectively (compared with 44.3, 51.7, and 41.3 respectively for RTOG 0938). Change in bowel score of >5 at 1, 2, and 5 years was 27%, 23%, and 25% (compared with 29.3, 28.7, and 30.6 respectively for RTOG 0938). Interestingly, there were a number of patients who reported improvement in their urinary score at 1, 2, and 5 years (26%, 36%, and 46%, respectively), The same held for patients who reported improvement in their bowel score at 1, 2 and 5 years (37%, 38% and 41%, respectively). Hence, the median urinary score was 6.25 lower at year 1, but only 2.08 lower at year 2 with no difference by year 5. The median bowel score showed zero difference at every time point. The 5-year bDFS in our cohort was 97.8% (compared to 91.3% in RTOG 0938). Our 10-year bDFS was 96%. Single modality PB with Cs131 provides excellent long-term bDFS, especially when compared to recently published RTOG 0938 as 47% of our patients had intermediate-risk disease (RTOG 0938 had low-risk disease only and only 5-year data). Our patients had modest changes in urinary and bowel QOL compared to baseline, also comparable to published SBRT data. At 5 years in our cohort, 46% and 41% reported improvement in their urinary and bowel EPIC scores. The reason for this needs to be explored.

A Phase I/II Dose-Escalation Study Evaluating the Safety of 21 Gy, 23 Gy, and 25 Gy for High Dose Rate (HDR) Prostate Brachytherapy: An Interim Toxicity Report.

Single-fraction high dose rate (HDR) prostate brachytherapy has shown improved actuarial biochemical control rates from 66% to 82% with dose escalation from 19 to 20.5 Gy, respectively, but is still inferior to the reported low dose rate brachytherapy control rates of over 90%. We aimed to identify whether dose escalation to 21, 23, and 25 Gy can be safely accomplished. Patients with previously untreated, pathologically confirmed, low-risk (cT1-T2a, Gleason ≤6, PSA <10 ng/mL) or favorable intermediate risk (Gleason 3+4, percentage of positive biopsy cores <50%, ≤1 NCCN intermediate risk factor) prostate adenocarcinoma were enrolled from a single institution. PSA and toxicity assessment were performed at baseline and at routine 6-month follow-ups. From May 9, 2018 to May 12, 2022, 18 patients were enrolled. None had received prior androgen deprivation therapy, 44% had low risk disease, and 61% were ECOG 0 at baseline. Median age was 68 years (total range: 43-79), and 83% were Caucasian. Eight patients received 21 Gy, nine patients received 23 Gy, and one patient received 25 Gy, with the 25 Gy cohort still accruing. The mean prostate size and range, determined by pre-operative prostate volume study on trans-rectal ultrasound, were as follows: 21Gy cohort (mean: 41.2cc; range: 21.9-63.1cc), 23Gy Cohort (mean: 41.2cc, range 28.3-71.7cc), 25Gy cohort (65.3cc). A median of 17 catheters (range: 16-20) were implanted. At a median follow-up of 35.7 months (range: IQR 4.4 - 50.2), only one grade 3 toxicity was reported, which was an ulcerative colitis (UC) flare noted in a patient whose UC was poorly controlled, requiring multiple courses of prednisone in the 6 months prior to his brachytherapy. Regarding toxicities attributable to therapy, fourteen and four patients experienced a grade 1 and 2 genitourinary toxicity respectively; four and four patients experienced a grade 1 and 2 reproductive system toxicity respectively; one patient experienced a grade 1 GI toxicity. Two patients needed foley catheters upon discharge, with neither requiring the foley long term. There were two treatment failures in the 21Gy cohort at 1.39 and 1.67 years from date of HDR brachytherapy; date of failure was defined by the first PSA 2.0ng/mL over nadir. Of these patients, one underwent focal salvage HDR, whilst the other underwent radical prostatectomy with only 1% of the volume involved by prostate cancer. Of note, there was seminal vesicle involvement on restaging prostate biopsy for the patient that underwent radical prostatectomy, however, this was not appreciated on the final prostatectomy specimen. Both patients have no evidence of disease currently. HDR brachytherapy appears well tolerated in patients with low to favorable intermediate risk prostate cancer at 21 and 23 Gy, with more accrual needed at 25Gy. Long-term follow-up needed to assess efficacy.

Risk Factors Predicting Relapse 10 Years Following Extreme Dose-Escalated SBRT for Intermediate-Risk Prostate Cancer: Is De-Intensification Feasible in Unfavorable Subgroups?

Adding short-term androgen-deprivation therapy (ADT) to radiotherapy is recommended in unfavorable intermediate-risk (UIR) prostate cancer (PCa). Data supporting the addition of ADT to stereotactic body radiotherapy (SBRT) in intermediate-risk (IR) patients are limited. Given ADT has well-documented toxicities, we sought to identify the UIR prognostic factors that predict for relapse following SBRT without ADT. We combined results from two mature multicenter trials to determine if extreme dose-escalated SBRT yielded UIR subgroups in which the omission of ADT may be considered. Between 2008 and 2011, two prospective national trials enlisted 39 centers to enroll 285 patients with IR PCa: 182 had Memorial Sloan Kettering (MSK) favorable intermediate-risk (FIR) and 103 had MSK UIF PCa. All were treated with a non-coplanar robotic SBRT platform using real-time tracking of implanted fiducials. Two dose regimens were used: 40Gy in 5 fractions of 8Gy, and 38Gy in 4 fractions of 9.5Gy. ADT was not allowed. Univariate and multivariate analyses using a Cox proportional hazards model was performed for relapse free survival (RFS): relapse included pathologic or radiographic failure, initiation of salvage or systemic therapy, or biochemical relapse by the nadir + 2 definition. Insufficient events prevented similar analyses for local control, metastasis-free and PCa-specific survival. Examined risk factors included dose regimen, clinical T-stage, Gleason score, pre-treatment PSA, % positive biopsy cores, and number of unfavorable risk factors (URFs). All reported rates are actuarial, using Kaplan-Meier method. Median follow-up was 8.1 years. 71 patients were followed 10 years. There were no statistically significant differences in rates of toxicity, local failure, RFS, overall nor metastasis-free survival between the two dose regimens. For the entire group, 10-year overall survival was 82.9%, RFS was 83.2%, and the local failure rate was 3.6%. On univariate analysis, primary Gleason pattern 4 (PGP4) and >2 URFs predicted for RFS. On multivariate analysis, only PGP4 (hazard ratio: 3.71, p = 0.0053) was statistically significant. Examining the UIR subgroup, the only predictor for RFS was PGP4 (HR: 3.64, p = 0.0253). 10-year RFS was 88.4% for FIR and 89.1% for UIR without PGP4; this fell to 58.5% in patients with a PGP4. Following dose-escalated SBRT monotherapy, 10-year RFS rates were favorable in UIR patients without PGP4. Extreme dose escalation appeared to effectively address UIR factors correlating with tumor bulk (i.e., CS T2b, >50% cores+, PSA 10-20), but was less effective with biologically aggressive pathology (PGP4). A randomized trial, ideally including genomic classification, would be necessary to determine if dose-escalated SBRT allows de-intensification (omission of ADT) in such biologically less aggressive UIR subgroups. The high relapse rate observed in UIR patients with PGP4 affirms the need for adjuvant ADT in this subgroup.

Active surveillance in favorable intermediate-risk prostate cancer: A single-center experience

PurposeTo report the long-term oncological outcomes of active surveillance (AS) in selected patients with favorable intermediate-risk (IR) prostate cancer (PCa). MethodsA retrospective database review of two academic centers was conducted to identify favorable IR PCa patients initially managed by AS between 2014 and 2022. Favorable IR PCa was defined by the presence of one single element of IR disease (i.e., PSA 10–20ng/mL, Gleason Grade Group [GG] 2, or cT2b). All patients were diagnosed and followed up according to a contemporary scheme, including MRI and image-guided biopsies. The primary endpoint was metastasis-free survival. ResultsA total of 57 patients met our inclusion criteria and the median follow-up was 56months. During follow-up, there were no cases of metastasis or death due to PCa, but 6 deaths due to competing causes. A total of 25 (44%) and 6 patients (11%) had definitive treatment and GG 3 reclassification during follow-up, respectively. In multivariable Cox hazard regression analysis, the risk of undergoing definitive treatment was significantly associated with PSA density>0.15 (HR: 4.82, 95% CI: 1.47 to 15; P=0.01) and PI-RADS 4-5 lesions on mpMRI (HR: 2.48, 95% CI: 1.06 to 5.19; P=0.006). Interestingly, tumor burden (P=0.3) and GG (P=0.7) on biopsy were not associated with definitive treatment. ConclusionsAS is a safe and valuable strategy for well-selected patients with favorable IR prostate cancer, with excellent oncological outcomes after five years’ follow-up. Level of evidence4

Increasing Use of Conservative Management of Low-Risk Prostate Cancer in the Veterans Affairs System from 2012 to 2021

Conservative management (CM), including either active surveillance or watchful waiting, is the preferred management strategy for men with low-risk prostate cancer. We sought to describe contemporary trends in CM among men with localized prostate cancer across the equal-access Veterans Affairs (VA) system. Using VA tumor registry data, we identified all men with a new diagnosis of biopsy-proven, clinically node-negative, non-metastatic prostatic adenocarcinoma from 2012 to 2021, excluding men with missing National Comprehensive Cancer Network risk group. We quantified the yearly proportion of patients with low and favorable intermediate-risk (FIR) prostate cancer undergoing conservative management and examined age-specific rates. Multivariable logistic regression was used to identify independent clinical predictors of CM among men with low-risk and FIR disease. The cohort included 86,415 patients with localized prostate cancer, of whom 20,290 (23.5%) had low risk and 25,447 (29.5%) had FIR disease. The proportion of men diagnosed with low-risk disease decreased from 27.7% in 2012 to 20.1% in 2021. The proportion of men with localized prostate cancer who were 70 years or older at diagnosis increased from 19.5% in 2012 to 46.4% in 2021, with similar increases seen across risk groups. The proportion of men with low-risk disease undergoing CM increased from 63.1% in 2012 to 86.6% in 2021. CM rates in 2021 among low-risk patients were largely consistent across age groups (50-59: 85.1%; 60-69: 87.4%; 70+: 86.3%). For FIR patients, CM rates increased among the subset with Gleason 6 disease (49.5% in 2012 to 80.7% in 2021). In multivariable models, independent predictors of CM in low-risk patients included older age, more recent year, lower PSA at diagnosis, North Atlantic or Pacific region, and presence of another cancer at diagnosis; similar predictors were found in FIR patients. Self-reported race (Black, White, or Other) was not associated with CM. While there was wide geographic variation in CM rates among low-risk patients early in the study period (2012-2014: 56.1% in Southeast region vs 74.1% in Pacific), these disparities resolved in recent years (2019-2021: 83.2% in Southeast vs 83.8% in Pacific). Rates of conservative management for localized prostate cancer increased dramatically over time in the VA, with over 85% of low-risk patients managed conservatively in 2021. Recent years showed no differences in CM rates by self-reported race, geographic region, or age group. Despite this progress, we observed a concomitant increase in the proportion of men 70 years or older diagnosed with localized prostate cancer, including low risk disease. This raises a need to consider strategies to reduce the diagnosis of low-risk disease in elderly Veterans.

Cross-Comparison Individual Patient Level Analysis of Three Gene Expression Signatures in Localized Prostate in over 50,000 Men

Risk stratification guides the management of localized prostate cancer. Multiple commercial gene expression biomarkers have been developed to improve estimates of prognosis, however the 22-gene Decipher genomic classifier (22-GC) is the only test with level 1 evidence supporting its use per NCCN guidelines. It is unknown whether other commercial signatures, Oncotype (GPS) or Prolaris (CCP), are sufficiently correlated to negate the differences in evidence supporting these commercial tests. Herein, we aim to perform a cross-comparison of these signatures in a large cohort of patients diagnosed with localized prostate cancer. Patients diagnosed with localized prostate cancer who underwent whole transcriptome gene expression microarray analysis on their primary tumor biopsy specimen were included. The 22-GC score was calculated by Veracyte using a commercially locked model. Individual genes in each of the GPS and CCP gene signatures were identified, and the gene weights in each signature were retrained for prediction of metastasis in a multi-institutional cohort of 1,574 men with long-term outcome data. This was performed to improve correlation performance of GPS and CCP given only the 22-GC was trained for prediction of metastasis. For each of the three signatures, both continuous and categorical scores were calculated. Linear regression and spearman correlations were calculated both on univariable and multivariable analyses adjusting for age, grade group, PSA, and T-stage. A total of 50,881 patients were included (15,379 (30.2%) NCCN low-risk, 14,773 (29.0%) favorable intermediate-risk, 15,544 (30.5%) unfavorable intermediate-risk, and 5,185 (10.2%) high/very high-risk) with a median age of 68 years, and a median PSA of 6.2 ng/mL. On linear regression, the GPS model had poor goodness-of-fit to the 22-GC with an R2 of 0.36, as did the CCP model to the 22-GC with an R2 of 0.32. For CCP, the linear sum of the 31-genes was also tested but had inferior performance (R2 0.28) compared to the reoptimized CCP model. Results were similar on multivariable analysis adjusting for age, PSA, clinical stage and grade group. Spearman correlation between the continuous GPS model scores and the 22-GC was moderate at 0.59, as was the correlation between CCP model and the 22-GC of 0.54. CCP is a measure of proliferation, but in 22-GC high-risk patients, the majority (64.1%) of patients had low-average proliferation and only 35.9% had high proliferation, potentially explaining the lack of strong correlation. There is minimal to moderate correlation between the 22-GC and GPS or CCP gene expression signatures tested. Therefore, these tests should not be viewed as interchangeable, and utilization should be based on the level of evidence supporting each gene expression biomarker.

5-Years Analysis of Effectivity and Toxicity of Ultra-Hypofractionated Proton Radiotherapy in the Treatment of Low- and Intermediate-Risk Prostate Cancer-A Retrospective Analysis.

We retrospectively analyzed the 5-year biochemical disease-free survival (bDFS) and occurrence of late toxicity in prostate cancer patients treated with pencil beam scanning (PBS) proton radiotherapy. In the period from January 2013 to June 2018, 853 patients with prostate cancer were treated with an ultra-hypofractionated schedule (36.25 GyE/five fractions). The mean PSA value was 6.7 (0.7-19.7) µg/L. There were 318 (37.3%), 314 (36.8%), and 221 (25.9%) patients at low (LR), favorable intermediate (F-IR), and unfavorable intermediate risk (U-IR), respectively. Neoadjuvant hormonal therapy was administered to 197 (23.1%) patients, and 7 (0.8%) patients had adjuvant hormonal therapy. The whole group of patients reached median follow-up time at 62.7 months, and their mean age was 64.8 (40.0-85.7) years. The bDFS rates and late toxicity profile were evaluated. Median treatment time was 10 (7-38) days. Estimated 5-year bDFS rates were 96.5%, 93.7%, and 91.2% for low-, favorable intermediate-, and unfavorable intermediate-risk groups, respectively. Cumulative late toxicity (CTCAE v4.0) of G2+ was as follows: gastrointestinal (GI)-G2: 9.1%; G3: 0.5%; genitourinary (GU)-G2: 4.3%, and no G3 toxicity was observed. PSA relapse was observed in 58 (6.8%) patients: 16 local, 22 lymph node, 4 bone recurrences, and 10 combined sites of relapse were detected. Throughout the follow-up period, 40 patients (4.7%) died, though none due to prostate cancer. Ultra-hypofractionated proton beam radiotherapy is an effective treatment for low- and favorable intermediate-risk prostate cancer, with long-term bDFS rates comparable to other techniques. It is promising for unfavorable intermediate-risk prostate cancer and has acceptable long-term GI and favorable GU toxicity.

LDR-Brachytherapy monotherapy appears unsuited for NCCN unfavorable intermediate-risk prostate cancer patients

BackgroundTo validate the subdivision of intermediate-risk (IR) prostate cancer (PCa) into favorable intermediate-risk (FIR) and unfavorable intermediate-risk (UIR) PCa in a historical patient cohort and to compare 2 different radiotherapy regimens. MethodsPatients with intermediate-risk (IR) PCa, treated either by 125J-LDR-brachytherapy monotherapy (BT) or by combined-modality radiation therapy (CRT), were retrospectively subclassified into FIR and UIR and reanalyzed with regard to biochemical recurrence-free survival (BRFS), metastasis-free survival (MFS), and prostate cancer-specific survival (CSS). Kaplan-Meier product-limit method and log-rank tests were applied to estimate survival probabilities and compare survival, respectively. Uni- and multivariable analyses were performed using Cox proportional hazard regression. ResultsOf 490 IR patients, 252 had received BT (86.5% FIR, 13.5% UIR), and 238 had received CRT (30% FIR, 70% UIR). Retrospective analysis revealed that BRFS at 10 years was 81% for BT, and 94% for CRT in FIR patients. For UIR patients, BRFS at 10 years was 37% for BT, and 89% for CRT. MFS at 10 years for FIR patients was 87% for BT, and 94% for CRT. For UIR patients MFS at 10 years was 78% for BT, and 95% for CRT. In multivariable analysis treatment (BT vs. CRT) was the single associated factor for biochemical recurrence, and for metastases in the UIR group (BFRS, P < 0.001, HR 16.07 (CI 4.23–61.10); MFS, P = 0.011, HR 8.43 (CI 1.62–43.9). ConclusionsSubclassification of IR prostate cancer into FIR and UIR subcategories appears mandatory. For FIR patients, outcomes after BT monotherapy were acceptable. However, clinical failure after 125J-LDR-BT in UIR patients was notably increased, suggesting that BT monotherapy was less successful in this risk group. In contrast, the outcome in UIR patients after CRT was excellent.

Impact of Multiparametric Magnetic Resonance Imaging for the Prediction of Extraprostatic Extension According to the National Comprehensive Cancer Network Risk Stratification in Prostate Cancer

Purpose: The accuracy of extraprostatic extension (EPE) on multiparametric magnetic resonance imaging (mpMRI) for the preoperative staging of prostate cancer (PCa) remains controversial. This study aimed to determine the effect of mpMRI for EPE prediction in the final pathology after radical prostatectomy (RP) according to the National Comprehensive Cancer Network (NCCN) risk stratification in patients with clinically localized PCa.Materials and Methods: This retrospective study analyzed 340 consecutive patients diagnosed with clinically localized PCa who underwent RP with preoperative mpMRI between March 2020 and December 2021. They were stratified according to the NCCN risk stratification into low (LR), favorable intermediate (FIR), unfavorable intermediate (UIR), and high risk (HR) groups to assess final pathological EPE. The accuracy of staging mpMRI was assessed in each group. Univariate and multivariate analyses evaluated the predictors of EPE in the final pathology after RP.Results: Preoperative mpMRI showed suspicious EPE in 87 patients (25.6%), whereas postoperative pathological evaluation revealed EPE in 137 patients (40.3%). The LR group showed relatively low sensitivity and positive predictive value compared with other groups. In the multivariate analysis, suspicious EPE on mpMRI was a significant predictive factor for EPE in the final pathology in the FIR, UIR, and HR groups (p=0.012, p=0.011, and p=0.001, respectively), whereas no correlation was observed in the LR group (p=0.711).Conclusions: A strong correlation was observed between suspicious EPE on mpMRI and EPE in the final pathology in the FIR, UIR, and HR groups but not in the LR group.

Endogenous testosterone density associates with predictors of tumor upgrading and disease progression in the low through favorable intermediate prostate cancer risk categories: analysis of risk factors and clinical implications

BackgroundThe study aimed to test the hypothesis that endogenous testosterone density (ETD), in the low through favorable intermediate PCa risk classes patients undergoing surgery, might be associated with disease progression.Materials and methodsETD, PSAD, and percentage of biopsy positive cores density (BPCD) were calculated in relation to prostate volume (PV). Tumor load density (TLD) was estimated as the tumor load (TL) ratio to prostate weight. ET was considered low if < 230 ng/dL. Tumor upgrading (ISUP > 2), upstaging (pT > 2) and their related features were investigated.Results433 patients were included, 249 (57.5%) from the favorable intermediate-risk class. Upgrading occurred in 168 (38.8%) cases and upstaging in 62 (14.3%). ETD above the median (9.9 ng/(dL x mL)), was discriminated by PSAD (AUC = 0.719; 95% CI: 0.671–0.766; p < 0.0001), BPCD (AUC = 0.721; 95% CI: 0.673–0.768; p < 0.0001), TLD (AUC = 0.674; 95% CI: 0.624–0.724; p < 0.0001) with accuracy improved by the multivariable model (AUC = 0.798; 95% CI: 0.724–0.811; p < 0.0001). In linear multivariable models as ETD increased, so did TLD (rc = 0.019; 95% CI: 0.014; 0.025; p < 0.0001), further increased by low ET (rc = 0.097; 95% CI: 0.017; 0.176; p = 0.017). After adjusting for clinical and pathological features, ETD correlated with TLD above the first quartile. Disease progression occurred in 43 (11.9%) patients, independently predicted by PSAD (hazard ratio, HR = 99.906; 95% CI: 6.519–1531.133; p = 0.001) and tumor upgrading (HR = 3.586; 95% CI: 3.586–6.863; p < 0.0001).ConclusionsETD was associated with unfavorable PCa, and men with tumor upgrading were at increased risk of disease progression. ETD was related to predictors of PCa progression and could provide pivotal biological information about aggressive disease.

Predicting absolute benefit in risk of metastasis of androgen deprivation therapy added to radiation therapy in patients with newly diagnosed prostate cancer using Prolaris.

5030 Background: Most patients would defer using androgen deprivation therapy (ADT) with radiation therapy (RT) when the number-needed-to-treat (NNT) exceeds 25 persons to prevent 1 from developing metastasis, corresponding to an absolute benefit of 4%.1 However, no tools for estimating personalized NNT or absolute benefit from ADT exist. We aimed to quantify personalized absolute benefit and NNT for persons receiving ADT added to single modality RT. Methods: The clinical cell-cycle risk (CCR) score combines the University of California, San Francisco’s Cancer of the Prostate Risk Assessment and the cell cycle progression molecular score to accurately assess prostate cancer aggressiveness. The effect of ADT added to RT was modeled using a 10-year risk of metastasis as a function of continuous CCR score for patients treated with RT alone. The relative benefit of ADT added to RT to reduce distant metastasis was modeled using published data from The Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) which utilized several prospectively randomized RT±ADT trials.2 The average absolute benefit was calculated for patients with CCR scores above and below a prespecified multimodality treatment threshold (MTT) using the distribution of scores in a cohort of patients commercially tested by Myriad Genetics. Results: The commercially tested cohort consisted of 56,485 patients spanning all National Comprehensive Cancer Network risk categories (33.7% very low/low risk, 29.8% favorable intermediate risk, 25.6% unfavorable intermediate risk, 11.0% high/very high risk), with 87.2% having CCR scores at or below the MTT and 12.7% with CCR scores above the threshold. The average absolute benefit of ADT treatment was 0.86% (NNT=116) for patients with CCR scores below the MTT and 8.2% (NNT=12) for patients with CCR scores above the MTT. Patients with CCR scores at precisely the MTT had a predicted absolute benefit of 3.7% (NNT=27). Conclusions: The Prolaris test can accurately predict an individual's benefit of adding ADT to RT, and the risk threshold is consistent with patient attitudes about when to use or omit ADT. 1. Spratt DE, Tward JD: IJROBP 108:899-902, 2020. 2. Kishan AU, Sun Y, Hartman H, et al. Lancet Oncol 23:304-316, 2022.

Recommendations for patients with prostate cancer who wish to undergo a kidney transplant

Over the past half a century, kidney transplants have increased significantly and more patients that are elderly are receiving kidney transplants. As a result, the eligibility of patients with prostate cancer who wish to receive a kidney transplant has become a significant issue facing the transplant community. Many questions have arisen because prostate cancer is an extremely variable disease that many times do not harm the patients but at other times, can cause the death of the patient.If a patient has prostate cancer, should he be allowed to receive a kidney transplant? Should he receive the transplant after treatment for prostate cancer or without such treatment? How should the transplant community determine his eligibility? Most agree that those with high-risk prostate cancer should be treated first and have a waiting period prior to kidney transplant. Almost all low-risk prostate cancer patients are candidates for active surveillance. More and more urologists are doing active surveillance for favorable intermediate risk prostate cancer patients. We believe that all patients who are reasonable candidates for active surveillance based on the National Comprehensive Cancer Network (NCCN) guidelines for prostate cancer are reasonable candidates for kidney transplant without treatment for prostate cancer. We recommend using a combination of shared-decision making that involves prostate cancer risk-stratification as well as adjunctive tests such as imaging with multiparametric MRI (mpMRI) and genomic testing such as Decipher, Oncotype DX or Polaris, in order to inform whether or not patients with prostate cancer can receive a kidney transplant without treatment for prostate cancer.

PO-1499 Extracranial stereotactic radiotherapy in low and favourable intermediate risk prostate cancer

PO-1499 Extracranial stereotactic radiotherapy in low and favourable intermediate risk prostate cancer

Expanding the role of PSMA PET in active surveillance

IntroductionAccurate grading at the time of diagnosis is fundamental to risk stratification and treatment decision making, particularly for men being considered for Active Surveillance (AS). With the introduction of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) there has been considerable improvement in sensitivity and specificity for the detection and staging of clinically significant prostate cancer. Our study aims to determine the role of PSMA PET/CT in men with newly diagnosed low or favourable intermediate risk prostate cancer to better select men for AS.MethodThis is a retrospective single centre study performed from January 2019 and October 2022. This study includes men identified from electronic medical record system who had undergone a PSMA PET/CT following newly diagnosed low or favourable-intermediate risk prostate cancer. Primary outcome was to assess the change in management for men being considered for AS following PSMA PET/CT results on the basis of PSMA PET characteristics.ResultsIn total, there were 11 of 30 men (36.67%) who were assigned management by AS and 19 of 30 men (63.33%) who had definitive treatment. 15 of the 19 men that needed treatment had concerning features on PSMA PET/CT results. Of the 15 men with concerning features on PSMA PET, 9 (60%) men were found to have adverse pathological features on final prostatectomy features.ConclusionThis retrospective study suggests that PSMA PET/CT has potential to influence the management of men with newly diagnosed prostate cancer that would otherwise be appropriate for active surveillance.

A modeling study to estimate prostate cancer-specific mortality on active surveillance for men with favorable intermediate-risk prostate cancer: Results from the SEARCH cohort.

Limited data exist to help surgeons decide between active surveillance (AS) versus treatment for men with favorable intermediate risk (FIR) prostate cancer. To estimate the theoretical excess risk of prostate cancer-specific mortality (PCSM) with AS versus radical prostatectomy (RP), we determined the risk of PCSM in FIR men undergoing RP and modeled the PCSM risk for AS using a range of increased PSCM scenarios ranging from 1.25x to 2x higher relative to RP. We retrospectively reviewed data from men undergoing RP from 1988 to 2017 at 8 Veterans Affairs hospitals within the SEARCH cohort. Men with FIR PC were identified using the NCCN risk criteria. Risk of PCSM at 5, 10, and 15 years after RP was estimated. Using these estimates, PCSM was then modeled for AS using a range of increased risk of PCSM relative to RP ranging from 1.25x to 2x higher. For the 920 FIR men identified, 5-, 10-, and 15-year survival estimates for PCSM after RP were 99.9%, 99.0%, and 97.8%, respectively. If the risk of PCSM on AS were 1.25-2x greater than RP, there would be 0.54%-2.17% excess risk of PCSM at 15 years. The risk of death for FIR after RP is very low. Assuming even modestly increased PCSM with AS versus RP, the excess risk of death for AS in FIR is low even up to 15 years. These data support the consideration of AS as a relatively safe alternative to RP in FIR men, though prospective randomized trials are needed to validate these findings.

Use of Active Surveillance vs Definitive Treatment Among Men With Low- and Favorable Intermediate–Risk Prostate Cancer in the US Between 2010 and 2018

This cross-sectional study of data from the Surveillance, Epidemiology and End Results database assesses temporal trends in the use of active surveillance and watchful waiting vs definitive treatment in men with low- and favorable intermediate–risk prostate cancer in the US between 2010 and 2018.