Unfavorable Prostate Cancer Research Articles

Survival outcomes in men with unfavorable intermediate-risk and high-risk prostate cancer treated with prostate-only versus whole pelvic radiation therapy.

264 Background: Men with unfavorable intermediate-risk (UIR-PCa) or high-risk prostate cancer (HR-PCa) are often treated with definitive external beam radiotherapy (EBRT) plus androgen deprivation therapy (ADT). Treatment is frequently intensified by electively treating the pelvic lymph nodes with whole pelvis radiotherapy (WPRT), but practice patterns differ and the benefits of WPRT are not clearly defined, with mixed results from clinical trials. The recent POP-RT trial showed improved biochemical control with WPRT but most patients were staged with PET/CT scan. We hypothesized that men treated with WPRT would have improved overall survival (OS) relative to men treated with prostate-only radiotherapy in patients staged using conventional imaging. Methods: Men diagnosed between 2008-2015 with UIR or high-risk prostate cancer were retrospectively reviewed from the National Cancer Database (n = 28,724). Patients with involved nodes or distant metastases were excluded. Men received EBRT to a dose of 72-86.4 Gy and either prostate-only RT ± ADT (n = 13,549) or WPRT plus prostate RT ± ADT (n = 15,175). WPRT was delivered using a dose range of 40-50.4 Gy (1.8 – 2.0 Gy/fraction). The MSKCC nomogram was used to calculate risk of lymph node involvement. Unweighted or inverse probability of treatment weighting (IPTW) was used to perform multivariable analysis (MVA) using Cox regression modeling to compare OS hazard ratios, accounting for age, race, year of diagnosis, Charlson-Deyo comorbidity score, insurance status, education, income, treatment facility type, PSA, Gleason score, clinical T-stage, use of ADT, lymph node risk score, and radiation dose. Results: 53% of men received WPRT, with national utilization of WPRT increasing from 2008 to 2015. For every 1% increase in risk of lymph node involvement, there was a 1% increased risk of death ( P<.001). WPRT trended toward improved OS in all men with UIR or high-risk (Hazard Ratio (HR): 0.95 [95% Confidence Interval: 0.90-1.006], P=.07). WPRT correlated with improved OS in men with grade group 5 (GG5) disease (HR: 0.87 [0.78-0.98]. P=.02) or risk of lymph node involvement ≥ 10% (HR: 0.93 [0.87-0.99], P=.03). Conclusions: WPRT is associated with improved OS in men with a lymph node risk score ≥ 10% or GG5 disease. These results complement the recent POP-RT randomized trial in mostly PET/CT-staged patients, demonstrating that a more heterogenous population of men staged without functional imaging appears to benefit from WPRT.

The Dilemma of Misclassification Rates in Senior Patients With Prostate Cancer, Who Were Treated With Robot-Assisted Radical Prostatectomy: Implications for Patient Counseling and Diagnostics.

ObjectivesThere is a recent paradigm shift to extend robot-assisted radical prostatectomy (RARP) to very senior prostate cancer (PCa) patients based on biological fitness, comorbidities, and clinical PCa assessment that approximates the true risk of progression. Thus, we aimed to assess misclassification rates between clinical vs. pathological PCa burden.Materials and MethodsWe compared senior patients with PCa ≥75 y (n = 847), who were propensity score matched with younger patients <75 y (n = 3,388) in a 1:4 ratio. Matching was based on the number of biopsy cores, prostate volume, and preoperative Cancer of the Prostate Risk Assessment (CAPRA) risk groups score. Multivariable logistic regression models (LRMs) predicted surgical CAPRA (CAPRA-S) upgrade, which was defined as a higher risk of the CAPRA-S in the presence of lower-risk preoperative CAPRA score. LRM incorporated the same variables as propensity score matching. Moreover, patients were categorized as low-, intermediate-, and high-risk, preoperative and according to their CAPRA and CAPRA-S scores.ResultsSurgical CAPRA risk strata significantly differed between the groups. Greater proportions of unfavorable intermediate risk (39 vs. 32%) or high risk (30 vs. 28%; p < 0.001) were observed. These proportions are driven by greater proportions of International Society of Urological Pathology (ISUP) Gleason Grade Group 4 or 5 (33 vs. 26%; p = 0.001) and pathological tumor stage (≥T3a 54 vs. 45%; p < 0.001). Increasing age was identified as an independent predictor of CAPRA-S-based upgrade (age odds ratio [OR] 1.028 95% CI 1.02–1.037; p < 0.001).ConclusionApproximately every second senior patient has a misclassification in (i.e., any up or downgrade) and each 4.5th senior patient specifically has an upgrade in his final pathology that directly translates to an unfavorable PCa prognosis. It is imperative to take such substantial misclassification rates into account for this sensitive PCa demographic of senior men. Future prospective studies are warranted to further optimize PCa workflow and diagnostics, such as to incorporate modern imaging, molecular profiling and implement these into biopsy strategies to identify true PCa burden.

SC187 - ABO blood group and unfavorable prostate cancer features after radical prostatectomy: retrospective study on 1149 patients

SC187 - ABO blood group and unfavorable prostate cancer features after radical prostatectomy: retrospective study on 1149 patients

PD65-09 ROLE OF PROSTATE HEALTH INDEX TO PREDICT GLEASON SCORE UPGRADING AND HIGH-RISK PROSTATE CANCER IN RADICAL PROSTATECTOMY SPECIMEN

You have accessJournal of UrologyProstate Cancer: Detection & Screening VII (PD65)1 Sep 2021PD65-09 ROLE OF PROSTATE HEALTH INDEX TO PREDICT GLEASON SCORE UPGRADING AND HIGH-RISK PROSTATE CANCER IN RADICAL PROSTATECTOMY SPECIMEN Hwanik Kim, Jung Kwon Kim, Hakmin Lee, Sangchul Lee, Jong Jin Oh, Seong jin Jeong, Seok-Soo Byun, Sung Kyu Hong, and Changhee Ye Hwanik KimHwanik Kim More articles by this author , Jung Kwon KimJung Kwon Kim More articles by this author , Hakmin LeeHakmin Lee More articles by this author , Sangchul LeeSangchul Lee More articles by this author , Jong Jin OhJong Jin Oh More articles by this author , Seong jin JeongSeong jin Jeong More articles by this author , Seok-Soo ByunSeok-Soo Byun More articles by this author , Sung Kyu HongSung Kyu Hong More articles by this author , and Changhee YeChanghee Ye More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002109.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate health index (PHI) seems to be a simple and inexpensive test for a multivariant approach to prostate cancer (PCa) screening and management. The PHI improves cancer prediction at initial and extended biopsy stages and even the disease recurrence after radical prostatectomy (RP). In this study, we aimed to evaluate the role of PHI in localized PCa and whether they are independent predictors of Gleason score (GS) upgrading at RP specimen in GS 3 + 3 PCa, unfavorable or high risk PCa or adverse pathologic feature in RP specimen. METHODS: 300 patients with prostate specific antigen ≥3ng/mL, PHI and prostate biopsy were retrospectively included in the study. The primary study outcomes are PCa and clinically significant PCa (csPCa) diagnostic rate of PHI, and GS upgrading rate at RP specimen. The secondary outcomes are the comparison between GS upgrading and non-upgrading group, GS upgrading and high-risk PCa (International Society of Urological Pathology Grade Group [ISUP GG] ≥3 or ≥pT3a) predictability of preoperative clinical factors. RESULTS: Overall, 139 (46.3%) and 92 (30.7%) were diagnosed with PCa and csPCa, respectively. GS upgrading rate was 38.8% in total patients with RP. Significant differences were shown in the total prostate volume (p=0.014), the rate of ISUP GG at biopsy (p=0.001), and the proportion of ISUP GG at RP (p=0.016). PHI valued ≥55 (p=0.032) and presence of PIRADS lesion ≥4 (p=0.008) were the significant predictors of GS upgrading in ISUP GG1. In addition, PHI grouping (p=0.016) can predict significantly ISUP GG ≥3 at RP. PHI (p=0.039) can also predict adverse pathologic feature (≥pT3a) in RP specimen. CONCLUSIONS: PHI can predict GS upgrading in combination with PIRADS lesions ≥4 in ISUP GG1. PHI alone can evaluate the possibility of high-risk PCa after surgery as well. Source of Funding: This study was supported by institutional grant (02-2020-021) from the Seoul National University Bundang Hospital Research Fund © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1155-e1156 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hwanik Kim More articles by this author Jung Kwon Kim More articles by this author Hakmin Lee More articles by this author Sangchul Lee More articles by this author Jong Jin Oh More articles by this author Seong jin Jeong More articles by this author Seok-Soo Byun More articles by this author Sung Kyu Hong More articles by this author Changhee Ye More articles by this author Expand All Advertisement Loading ...

MP50-12 PELVIC LYMPH NODE DISSECTION AT RADICAL PROSTATECTOMY FOR INTERMEDIATE RISK PROSTATE CANCER: ASSESSING UTILITY AND NODAL METASTASES WITHIN A STATEWIDE QUALITY IMPROVEMENT CONSORTIUM

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy III (MP50)1 Sep 2021MP50-12 PELVIC LYMPH NODE DISSECTION AT RADICAL PROSTATECTOMY FOR INTERMEDIATE RISK PROSTATE CANCER: ASSESSING UTILITY AND NODAL METASTASES WITHIN A STATEWIDE QUALITY IMPROVEMENT CONSORTIUM Joshua Kuperus, Conrad Tobert, Ji Qi, and Brian Lane Joshua KuperusJoshua Kuperus More articles by this author , Conrad TobertConrad Tobert More articles by this author , Ji QiJi Qi More articles by this author , and Brian LaneBrian Lane More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002076.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: AUA guidelines for localized prostate cancer (PCa) states that pelvic lymph node dissection (PLND) is indicated for patients with unfavorable intermediate and high-risk disease and should be considered in favorable intermediate risk patients. NCCN guidelines recommend PLND when risk for nodal disease is ≥2%. Given the discrepancy in recommendations, we sought to assess which patients with intermediate risk PCa would benefit from a PLND across the Michigan Urological Surgery Improvement Collaborative. METHODS: Data regarding all robot-assisted radical prostatectomy (RARP) (03/2012-10/2020) were prospectively collected, including patient and surgeon characteristics. RESULTS: Among 8,664 men undergoing RARP for intermediate-risk PCa, 80.2% were performed with PLND (n = 6951), of which 3.0% were LN+ (n=207). According to the current AUA risk stratification system, 1.2% of favorable intermediate risk PCa and 4.9% of unfavorable intermediate risk PCa were positive for lymph node metastases (LN+). There were also differences in the LN+ rates among the subgroups of each of these categories (0.0% - 1.3%), and (3.7% – 5.2%). Additional factors, not accounted for in this system, that were associated with higher LN+ rates include ≥3 cores involved, ≥35% involvement at any core, and unfavorable genomic classifier result. CONCLUSIONS: When to perform PLND remains up for debate. Our data suggest patients with favorable intermediate risk prostate cancer should only undergo PLND if they have ≥3 cores involved, ≥35% involvement at any core, and/or unfavorable genomic classifier result. Source of Funding: The corresponding author would like to thank the Betz Family Endowment for Cancer Research for their continued support. Funding was provided to B.R. Lane in part by the Spectrum Health Foundation (RG0813-1036). The authors would like to acknowledge the support provided the Value Partnerships program at Blue Cross Blue Shield of Michigan © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e890-e891 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joshua Kuperus More articles by this author Conrad Tobert More articles by this author Ji Qi More articles by this author Brian Lane More articles by this author Expand All Advertisement Loading ...

Regional differences in patient age and prostate cancer characteristics and rates of treatment modalities in favorable and unfavorable intermediate risk prostate cancer across United States SEER registries

BackgroundIntermediate risk (IR) prostate cancer (PCa) is a highly heterogeneous entity and can be distinguished into favorable and unfavorable IR PCa according to biopsy, PSA and cT-stage characteristics. These differences may translate into differences in treatment type. MethodsWe tested for differences in PCa tumor characteristics and differences in active treatment rates (radical prostatectomy [RP], external beam radiotherapy [EBRT]) according to Surveillance, Epidemiology and End Results (SEER) registry (2010−2015) in favorable and unfavorable IR PCa. Data were stratified according to individual SEER registries. Further analyses additionally adjusted for PCa baseline characteristics (PSA, cT stage, biopsy Gleason group grading [GGG], percentage of positive biopsy cores). ResultsTabulations according to SEER registries showed that, in favorable IR vs. unfavorable IR, the rates of RP and EBRT respectively ranged from 30.0 to 54.3% vs. 30.3–55.5 % and 8.3–44.7 % vs. 11.5–45.5 %. Differences in age and baseline PCa tumor characteristics also existed in both favorable and unfavorable IR across SEER registries. After adjustment for those baseline patient and PCa characteristics (PSA, cT stage, GGG, percentage of positive biopsy cores), RP and EBRT rates exhibited virtually no residual differences across individual SEER registries, in both favorable (36.0–41.0 % and 26.8–28.1 %) and unfavorable IR PCa (39.2−42.0% and 31.1–33.5 %). ConclusionImportant differences may be identified in treatment rates within the examined 18 SEER registries in favorable and in unfavorable IR PCa. However, the observed differences are virtually entirely explained by differences in baseline PCa characteristics.

Cover Image

AbstractThe cover image is based on the Original Article A 4K score/MRI based nomogram for predicting prostate cancer, clinically significant prostate cancer and unfavorable prostate cancer by Vinayak Wagaskar et al., https://doi.org/10.1002/cnr2.1357. image

PH-0661 survival analysis of brachytherapy alone vs. EBRT in unfavorable intermediate-risk prostate cancer

PH-0661 survival analysis of brachytherapy alone vs. EBRT in unfavorable intermediate-risk prostate cancer

Abstract CT257: Phase 3 multicenter randomized trial of PSMA PET/CT prior to definitive radiation therapy for unfavorable intermediate-risk or high-risk prostate cancer [PSMA dRT]: Study Protocol

Abstract Background: Definitive radiation therapy (dRT) is an effective initial treatment of intermediate-risk (IR) and high-risk (HR) prostate cancer (PCa). PSMA PET/CT is superior to standard of care imaging (CT, MRI, bone scan) for detecting regional and distant metastatic PCa. PSMA PET/CT thus has the potential to guide patient selection and the planning for dRT and improve patient outcomes. Methods: This is a multicenter randomized phase 3 trial (NCT04457245). We will randomize 312 patients to proceed with standard dRT (control Arm, n=150), or undergo a PSMA PET/CT scan at the study site (both 18F-DCFPyL and 68Ga-PSMA-11 can be used) prior to dRT planning (intervention arm, n = 162). dRT will be performed at the treating radiation oncologist facility. In the control arm, dRT will be performed as routinely planned. In the intervention arm, the treating radiation oncologist can incorporate PSMA PET/CT findings into the RT planning. Androgen deprivation therapy (ADT) is administered per discretion of the treating radiation oncologist and may be modified as a result of the PSMA PET/CT results. We assume that approximately 8% of subjects randomized to the PSMA PET arm will be found to have M1 disease and thus will be more appropriate candidates for long-term systemic or multimodal therapy, rather than curative intent dRT. PET M1 patients will thus not be included in the primary endpoint analysis. The primary endpoint is the success rate of patients with unfavorable IR and HR PCa after standard dRT versus PSMA PET-based dRT. Secondary Endpoints (whole cohort) include progression free survival (PFS), metastasis-free survival after initiation of RT, overall survival (OS), % of change in initial treatment intent and Safety. Discussion: This is the first randomized phase 3 prospective trial designed to determine whether PSMA PET/CT molecular imaging can improve outcomes in patients with PCa who receive dRT. In this trial the incorporation of PSMA PET/CT may improve the success rate of curative intent radiotherapy in two ways: to optimize patient selection as a biomarker and to personalizes the radiotherapy plan. Citation Format: Jeremie Calais, Shaojun Zhu, Nader Hrimas, Matthias Eiber, Boris Hadaschik, Martin Stuschke, Ken Herrmann, Johannes Czernin, Amar U. Kishan, Nicholas G. Nickols, David Elashoff, Wolfgang Fendler. Phase 3 multicenter randomized trial of PSMA PET/CT prior to definitive radiation therapy for unfavorable intermediate-risk or high-risk prostate cancer [PSMA dRT]: Study Protocol [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT257.

Complete resolution of a giant multilocular prostatic cystadenoma following androgen deprivation therapy: an illustrative case report

ABSTRACTGiant multilocular prostatic cystadenoma (GMPC) is a rare benign pelvic mass for which complete surgical resection is an accepted treatment of choice. This report presents the first case of complete resolution of GMPC following a 3-year course of luteinising hormone-releasing hormone agonist alongside external beam radiotherapy for the concurrent treatment of unfavorable intermediate-risk prostate cancer. In addition to illustrating the imaging features of the effect of androgen deprivation therapy (ADT) and radiotherapy on GMPC regression, this case provides evidence for considering ADT as an alternative, noninvasive GMPC treatment option in patients in whom surgical treatment is either contraindicated or can be made less invasive by reducing the size of GMPC prior to its removal.

Stereotactic body radiation therapy (SBRT) versus conventionally fractionated external beam radiation therapy in unfavorable intermediate-risk prostate cancer: An inverse propensity matched analysis.

e17054 Background: Conventionally fractionated radiotherapy (CFRT) or moderately hypofractionated radiotherapy (MFRT) ± short-course androgen deprivation therapy (ADT) is commonly employed for unfavorable intermediate-risk (UIR) prostate cancer. Stereotactic body radiation therapy (SBRT) has not been widely adopted, but may have radiobiologic advantages over more conventionally fractionated treatments. We hypothesized that radiotherapy dose-escalation with SBRT (35-40Gy in ≤5 fractions) is associated with improved overall survival (OS) relative to biologically equivalent doses of CFRT (72-86.4Gy in 1.8-2.0Gy/fraction) or MFRT (≥60Gy in 2.4-3.2Gy/fraction) ± ADT. Methods: The National Cancer Database (NCDB) was used to identify 28,028 men with UIR prostate cancer who received CFRT with (n = 12,872) or without ADT (n = 12,984), MFRT with (n = 251) or without ADT (n = 281), and SBRT with (n = 212) or without ADT (n = 1,428). SBRT+ADT patients were excluded due to low patient numbers. Inverse probability of treatment weighting was used to balance measured confounders. Unweighted- and weighted- multivariable analysis (MVA) using Cox regression was used to compare OS hazard ratios. Results: Relative to CFRT without ADT, CFRT+ADT (Hazard Ratio (HR): 0.92, [95% Confidence Interval: 0.87-0.97], P = .002) and SBRT without ADT (HR: 0.74 [0.61-0.89], P = .002) were both associated with improved OS on MVA. Relative to CFRT+ADT, SBRT without ADT correlated with improved OS on MVA (HR: 0.81 [0.67-0.99], P = .04). Weight-adjusted MVA demonstrated that SBRT (HR: 0.80 [0.65-0.98], P = .036) and ADT (HR: 0.91 [0.86-0.97], P = .002) correlated with improved OS. SBRT was not associated with improved OS relative to MFRT. Conclusions: Using inverse propensity treatment weighting, we adjusted for age, comorbidity score, and tumor factors, and observed a significant overall survival benefit in favor of administering dose-escalated SBRT over CFRT+ADT. To our knowledge, this is the first study to show that SBRT is associated with improved OS relative to CFRT for men with UIR prostate cancer. Together, this suggests that SBRT offers a cheaper and shorter course of therapy that mitigates COVID-19 exposure, which also is associated with improved OS relative to CFRT for UIR prostate cancer and may obviate the need for ADT in this population. While we await results from several ongoing clinical trials, we believe this study lends support to the use of SBRT in men with UIR prostate cancer.

Phase 3 multicenter randomized trial of PSMA PET/CT prior to definitive radiation therapy for unfavorable intermediate-risk or high-risk prostate cancer [PSMA dRT]: study protocol

BackgroundDefinitive radiation therapy (dRT) is an effective initial treatment of intermediate-risk (IR) and high-risk (HR) prostate cancer (PCa). PSMA PET/CT is superior to standard of care imaging (CT, MRI, bone scan) for detecting regional and distant metastatic PCa. PSMA PET/CT thus has the potential to guide patient selection and the planning for dRT and improve patient outcomes.MethodsThis is a multicenter randomized phase 3 trial (NCT04457245). We will randomize 312 patients to proceed with standard dRT (control Arm, n = 150), or undergo a PSMA PET/CT scan at the study site (both 18F-DCFPyL and 68Ga-PSMA-11 can be used) prior to dRT planning (intervention arm, n = 162). dRT will be performed at the treating radiation oncologist facility. In the control arm, dRT will be performed as routinely planned. In the intervention arm, the treating radiation oncologist can incorporate PSMA PET/CT findings into the RT planning. Androgen deprivation therapy (ADT) is administered per discretion of the treating radiation oncologist and may be modified as a result of the PSMA PET/CT results. We assume that approximately 8% of subjects randomized to the PSMA PET arm will be found to have M1 disease and thus will be more appropriate candidates for long-term systemic or multimodal therapy, rather than curative intent dRT. PET M1 patients will thus not be included in the primary endpoint analysis. The primary endpoint is the success rate of patients with unfavorable IR and HR PCa after standard dRT versus PSMA PET-based dRT. Secondary Endpoints (whole cohort) include progression free survival (PFS), metastasis-free survival after initiation of RT, overall survival (OS), % of change in initial treatment intent and Safety.DiscussionThis is the first randomized phase 3 prospective trial designed to determine whether PSMA PET/CT molecular imaging can improve outcomes in patients with PCa who receive dRT. In this trial the incorporation of PSMA PET/CT may improve the success rate of curative intent radiotherapy in two ways: to optimize patient selection as a biomarker and to personalizes the radiotherapy plan.Clinical trial registrationUCLAIND#147591○ Submission: 02.27.2020○ Safe-to-proceed letter issued by FDA: 04.01.2020UCLA IRB #20–000378ClinicalTrials.gov Identifier NCT04457245. Date of Registry: 07.07.2020.EssenEudraCT 2020–003526-23

Patient Preferences and Treatment Decisions for Prostate Cancer: Results From A Statewide Urological Quality Improvement Collaborative

ObjectivesTo examine the relationship between influential factors and treatment decisions among men with newly diagnosed prostate cancer (PCa). MethodsWe identified men in the Michigan Urological Surgery Improvement Collaborative registry diagnosed with localized PCa between 2018-2020 who completed Personal Patient Profile-Prostate. We analyzed the proportion of active surveillance (AS) between men who stated future bladder, bowel, and sexual problems (termed influential factors) had “a lot of influence” on their treatment decisions versus other responses. We also assessed the relationship between influential factors, confirmatory testing results and choice of AS. ResultsA total of 509 men completed Personal Patient Profile-Prostate. Treatment decisions aligned with influential factors for 88% of men with favorable risk and 49% with unfavorable risk PCa. A higher proportion of men who identified bladder, bowel and sexual concerns as having “a lot of influence” on their treatment decision chose AS, compared with men with other influential factors, although not statistically significant (44% vs 35%, P = .11). Similar results were also found when men were stratified based on PCa risk groups (favorable risk: 78% vs 67%; unfavorable risk: 17% vs 9%, respectively). Despite a small sample size, a higher proportion of men with non-reassuring confirmatory testing selected AS if influential factors had “a lot of influence” compared to “no influence” on their treatment decisions. ConclusionMen's concerns for future bladder, bowel, and sexual function problems, as elicited by a decision aid, may help explain treatment selection that differs from traditional clinical recommendation.

Trimodal therapy with high-dose-rate brachytherapy and hypofractionated external beam radiation combined with long-term androgen deprivation for unfavorable-risk prostate cancer

PurposeTo assess the outcomes of high-dose-rate (HDR) brachytherapy and hypofractionated external beam radiation therapy (EBRT) combined with long-term androgen deprivation therapy (ADT) in very-high-risk (VHR) versus high-risk (HR) prostate cancer (PCa), as defined in the National Comprehensive Cancer Network (NCCN) criteria.MethodsData from 338 consecutive HR or VHR PCa patients who had undergone this tri-modal therapy between 2005 and 2018 were retrospectively analyzed. Biochemical recurrence (BCR)-free, progression-free, overall, and cancer-specific survival (BCRFS/PFS/OS/CSS) rates were analyzed using the Kaplan–Meier method and Wilcoxon test. Cox regression models were used to evaluate candidate prognostic factors for survival. C‑indexes were used to assess model discrimination.ResultsWithin a median follow-up of 84 months, 68 patients experienced BCR, 58 had disease progression including only 3 with local progression, 27 died of any cause, and 2 died from PCa. The 5‑year BCRFS, PFS, OS, and CSS rates were 82.2% (HR 86.5%; VHR 70.0%), 90.0% (HR 94.3%; VHR 77.6%), 95.7% (HR, 97.1%; VHR, 91.8%), and 99.6% (HR, 100%; VHR, 98.0%), respectively. In multivariable analyses that adjusted for standard clinicopathologic features, the risk subclassification was associated both PFS and OS (p = 0.0003 and 0.001, respectively). Adding the risk subclassification improved the accuracy of models in predicting BCRFS, PFS, and OS.ConclusionWhile the outcome of this trimodal approach appears favorable, VHR PCa patients had significantly worse oncological outcomes than those with HR PCa. The NCCN risk subclassification should be integrated into prognostic tools to guide risk stratification, treatment, and follow-up for unfavorable PCa patients receiving this trimodal therapy.

A prospective clinical and transcriptomic feasibility study of oral-only hormonal therapy with radiation for unfavorable prostate cancer in men 70 years of age and older or with comorbidity.

Androgen deprivation therapy (ADT) improves outcomes in unfavorable-risk prostate cancer (PCa) treated with radiation therapy (RT). It was hypothesized that replacing luteinizing hormone-releasing hormone (LHRH) agonists with a 5-α-reductase inhibitor (5-ARI) would improve hormonal health-related quality of life (HRQOL) without differentially suppressing androgen-responsive (AR) gene expression. Patients with localized unfavorable-risk PCa, aged ≥70 years or Charlson Comorbidity Index score ≥2 were treated with oral ADT (oADT), consisting of 4 months of bicalutamide, a 5-ARI, and RT at 78 Gy. The primary end point was Expanded Prostate Cancer Index Composite HRQOL at 6 months ≤30%, and improvement compared with a synchronous standard of care (SOC) cohort receiving 4 months of bicalutamide and long-term LHRH agonist with RT. RNA sequencing was performed from matched pre-/post-ADT prostate tumor biopsies in a subset of men. Differential gene and pathway expressional changes were examined using gene set enrichment. Between 2011 and 2018, 40 and 30 men were enrolled in the oADT and SOC cohorts, respectively. Median follow-up was 40 months. Those with ≤30% decline in hormonal HRQOL at 6 months was 97% (oADT) and 93% (SOC). The average 6-month hormonal decline was 1% (oADT) versus 12% (SOC; P = .04). The 4-year freedom from biochemical failure was 88% (oADT) versus 81% (SOC; P = .48). RNA sequencing (n = 9) showed similar numbers of downregulated and upregulated genes between the treatment groups (fold-change = 2; false-discovery rate-adjusted P ≤ .05). Both treatments comparably decreased the expression of 20 genes in canonical androgen receptor signaling. For men with PCa undergoing RT, oral versus standard ADT may improve 6-month QOL and appears to have a similar impact on androgen-responsive gene expression.

A 4K score/MRI-based nomogram for predicting prostate cancer, clinically significant prostate cancer, and unfavorable prostate cancer.

BackgroundThe detection of prostate cancer requires histological confirmation in biopsy core. Currently, number of unnecessary prostate biopsies are being performed in the United States. This is due to the absence of appropriate biopsy decision‐making protocol.AimTo develop and validate a 4K score/multiparametric magnetic resonance imaging (mpMRI)‐based nomogram to predict prostate cancer (PCa), clinically significant prostate cancer (csPCa), and unfavorable prostate cancer (uPCa).Methods and ResultsRetrospective, single‐center study evaluating a cohort of 574 men with 4K score test >7% or suspicious digital rectal examination (DRE) or Prostate Imaging Reporting and Data System (PI‐RADS) scores 3, 4, or 5 on mpMRI that underwent systematic and/or mpMRI/ultrasound fusion–targeted prostate biopsy between 2016 and 2020. External cohort included 622 men. csPCa and uPCa were defined as Gleason score ≥3 + 4 and ≥4 + 3 on biopsy, respectively. Multivariable logistic regression analysis was performed to build nomogram for predicting PCa, csPCa, and uPCa. Validation was performed by plotting the area under the curve (AUC) and comparing nomogram‐predicted probabilities with actual rates of PCa, csPCa, and uPCa probabilities in the external cohort.4K score, a PI‐RADS ≥4, prostate volume and prior negative biopsy were significant predictors of PCa, csPCa, and uPCa. AUCs were 0.84, 0.88, and 0.86 for the prediction of PCa, csPCa, and uPCa, respectively. The predicted and actual rates of PCa, csPCa, and uPCa showed agreement across all percentage probability ranges in the validation cohort. Using the prediction model at threshold of 30, 30% of overall biopsies, 41% of benign biopsies, and 19% of diagnosed indolent PCa could be avoided, while missing 9% of csPCa.ConclusionThis novel nomogram would reduce unnecessary prostate biopsies and decrease detection of clinically insignificant PCa.

Neoadjuvant versus concurrent androgen deprivation therapy plus radiotherapy for unfavorable intermediate-risk and high-risk prostate cancer with low PSA.

243 Background: Dose-escalated radiotherapy (RT) with androgen-deprivation therapy (ADT) is a standard definitive treatment for localized prostate cancer (LPCa), but the optimal sequencing of hormone therapy with RT is unclear, with most patients treated with neoadjuvant ADT. Clinical trials addressing this question have not yielded definitive results. During COVID-19, there has been greater interest in neoadjuvant ADT as a way to delay initiation of RT to reduce risk of COVID transmission from daily RT visits with recent analysis from the NCDB showing that RT can be delayed for up to 6 months after neoadjuvant ADT. It is unclear if neoadjuvant ADT is appropriate for all patients or if select cohorts may benefit from concurrent ADT and upfront RT, such as patients with higher grade disease and low PSA who may have less hormone-responsive disease. Methods: Using the NCDB, we identified men diagnosed from 2004 to 2015 with NCCN unfavorable intermediate risk or high-risk adenocarcinoma of the prostate with a presenting PSA ≤ 5 ng/mL treated with definitive RT and either ADT initiated 2-4 months prior to RT (neoadjuvant ADT) or ADT started within 7 days of RT (concurrent ADT). OS was the primary endpoint. OS was estimated using the Kaplan-Meier method. Multivariable Cox proportional hazards analyses was performed using age, facility type, Charlson-Deyo comorbidity score, clinical T stage, and Gleason score. Results: 2393 patients were identified, with 2103 receiving neoadjuvant ADT and 290 receiving concurrent ADT. Multivariable analysis (MVA) showed that concurrent ADT was associated with a lower risk of death relative to patients receiving neoadjuvant ADT {hazard ratio (HR): 0.58 [95% confidence interval: 0.36-0.94], p = 0.02}. The number of days from diagnosis to the start of RT was not associated with worse OS (HR:[0.99-1.01], p = 0.61) on MVA. Age (HR = 1.03 [1.01-1.05], p = 0.002) and treatment at an academic center (HR: 0.71 [0.53-0.94], p = 0.02) were also significantly associated with OS on MVA. The benefit of concurrent ADT relative to neoadjuvant ADT was greatest in patients with Gleason 4 and Gleason 5 disease (HR: 0.31 [0.14-0.71], p = 0.005). Conclusions: For patients with unfavorable intermediate-risk or high-risk prostate cancer and a PSA ≤ 5 ng/mL, concurrent ADT and upfront RT was associated with improved OS compared to neoadjuvant ADT and RT. The associated benefit appeared to be more pronounced for Gleason Score ≥ 8. Results are hypothesis generating and require validation in a randomized trial.

Cancer treatment delays caused by the COVID-19 pandemic may not hinder outcomes.

Cancer treatment delays caused by the COVID-19 pandemic may not hinder outcomes.

Use of Warfarin or Direct Oral Anticoagulants and Risk of Prostate Cancer in PCBaSe: A Nationwide Case-Control Study.

Existing literature examining warfarin's association with prostate cancer (PCa) risk provides conflicting results, while the association with direct oral anticoagulants (DOACs) has not yet been studied. We investigated the association of warfarin and DOAC use on PCa risk among men within the population-based Prostate Cancer database Sweden (PCBaSe), using a case-control design. The study population included PCa cases diagnosed 2014–2016 and five age-matched PCa-free controls. Conditional logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CI) for PCa associated with warfarin and DOAC use, adjusted for marital status, education level, other drug use, and comorbidities. Among 31,591 cases and 156,802 controls, there were 18,522 (9.8%) warfarin and 4,455 (2.4%) DOAC users. Warfarin ever-use was associated with reduced risk of PCa overall (OR 0.92 95% CI 0.88–0.96) as were both past and current use. DOAC use was not associated with PCa risk. For some warfarin exposures, decreased risk was observed for unfavorable PCa (high risk/locally advanced/distant metastatic) but not with favorable PCa (low/intermediate risk). Increased risk of favorable PCa was observed for men whose initial warfarin exposure occurred in the 12 month period before diagnosis (OR 1.39; 95% CI 1.13–1.70). Our findings are consistent with previous publications reporting decreased PCa risk with warfarin exposure. Increased risk of favorable PCa suggests detection bias due to increased prostate specific antigen testing when starting on warfarin. Decreased overall PCa risk could reflect bias due to reduced biopsy rates among long-term warfarin users.

Stereotactic body radiotherapy versus conventional/moderate fractionated radiation therapy with androgen deprivation therapy for unfavorable risk prostate cancer

BackgroundUltrahypofractionation using stereotactic body radiotherapy (SBRT) is an increasingly utilized technique for men with prostate cancer (PC). The comparative efficacy of SBRT plus androgen deprivation therapy (ADT) compared to fractionated radiotherapy (EBRT) plus ADT in higher-risk prostate cancer is unknown.MethodsMen > 40 years old with localized PC treated with external beam radiation and concomitant ADT for curative intent between 2004 and 2016 were analyzed from the National Cancer Database. Patients who lacked ADT or risk stratification data were excluded. 558 men treated with SBRT versus 40,797 men treated with conventional or moderately hypofractionated EBRT were included. Patients were stratified by unfavorable intermediate (UIR) and high (HR) risk using NCCN criteria. Kaplan Meier and Cox proportional hazards were used to compare overall survival (OS) between RT modality, adjusting for age, race, and comorbidity index.ResultsWith a median follow up of 74 months, there was no difference in estimated 6-year OS between men treated with SBRT versus EBRT regardless of risk group. On multivariable analysis, there was no difference in risk of death for men treated with SBRT compared to EBRT (UIR: adjusted HR 1.09, 95% CI 0.68–1.74, p = .72; HR: adjusted HR 0.93, 95% CI 0.76–1.14, p = .51). On sensitivity analyses, when confining the cohort to men treated with NCCN-preferred dose fractionations, with no comorbidities, or < 65 years old, there remained no survival difference between treatment groups for both UIR and HR.ConclusionWithin study limitations, we found no difference in survival between SBRT+ADT and standard of care EBRT+ADT for UIR or HR PC. These results support recent NCCN guideline updates, which include SBRT as a non-preferred option for higher risk men. Prospective validation would further strengthen the evidence basis behind these recommendations.