Unfavorable Intermediate-risk Prostate Research Articles

PO0403: Effect of Androgen Deprivation Therapy in Addition to Brachytherapy-Based Dose Escalated Radiation Therapy for Men with Unfavorable Intermediate Risk Prostate Cancer

PO0403: Effect of Androgen Deprivation Therapy in Addition to Brachytherapy-Based Dose Escalated Radiation Therapy for Men with Unfavorable Intermediate Risk Prostate Cancer

Long-Term Outcomes Associated with Different High-Dose-Rate Brachytherapy Dose Regimens for Favorable and Unfavorable Intermediate Risk Prostate Cancer.

To present long-term efficacy outcomes of prostate high-dose-rate (HDR) brachytherapy monotherapy using 38 Gy in 4 fractions, 24 Gy in 2 fractions, and 27 Gy in 2 fractions for men with favorable and unfavorable intermediate risk prostate cancer. Patients treated with HDR brachytherapy monotherapy for NCCN favorable (FIR) or unfavorable (UIR) intermediate risk prostate cancer from 1999-2020 were identified in a prospectively maintained, single institution database. Patients with less than two years of follow-up and those treated with single fraction HDR brachytherapy were excluded. Biochemical failure was determined using Phoenix criteria. 10-year biochemical control (BC), local control (LC), and distant metastasis (DM) rates were estimated using the Kaplan-Meier method. Two hundred sixty-seven patients were included. One hundred eighty-nine had FIR and 78 had UIR prostate cancer, with median follow-up of 9.6 years and 7.2 years, respectively. Of the 189 patients with FIR prostate cancer, 59 (31.2%) received 38 Gy in 4 fractions, 26 (13.7%) received 24 Gy in 2 fractions, and 104 (55.0%) received 27 Gy in 2 fractions. Of the 78 patients with UIR prostate cancer, 20 (25.6%) received 38 Gy in 4 fractions, 11 (14.1%) received 24 Gy in 2 fractions, and 47 (60.2%) received 27 Gy in 2 fractions. Date ranges of treatment for the respective fractionation schedules were 1999-2010, 2007-2016, and 2009-2020. Upfront androgen deprivation therapy (ADT) was given to 12 (6.3%) patients with FIR and 10 (12.8%) patients with UIR. 10-year rates of BC for FIR and UIR patients were 90.1% and 78.8% (p = 0.004), respectively. 10-year rates of LC were 92.4% and 85.0% (p = 0.06), respectively. 10-year rates of DM were 1.9% and 4.7% (p = 0.12), respectively. For FIR patients, 10-year BC rates were 96.2% for patients receiving 38 Gy in 4 fractions vs. 86.3% (p = 0.07) for those treated with the 2-fraction regimens, while 10-year LC rates were 97.9% and 89.0% (p = 0.049), respectively. Within the UIR subset, the 10-year BC rates for patients receiving 38 Gy in 4 fractions and patients receiving treatment in 2 fractions were 95.0% and 70.6% (p = 0.038). 10-year LC rates were 100% and 77.8% (p = 0.045), respectively. 10-year BC rates by treatment schedule are shown in the table below. HDR brachytherapy monotherapy results in excellent long-term local control for intermediate risk prostate cancer. Improvements in biochemical and local disease control for patients treated with 38 Gy in 4 fractions warrants consideration of prospective study of optimal treatment dosing regimens.

High-Dose Rate Brachytherapy Alone for Treatment of Unfavorable Intermediate Risk Prostate Cancer: A Propensity-Score Matched Analysis.

To demonstrate the feasibility of high-dose rate brachytherapy (HDR BT) as monotherapy for unfavorable intermediate risk (UIR) prostate cancer by comparing survival outcomes of HDR BT alone against external beam radiation therapy (EBRT) + HDR BT boost, +/- androgen deprivation therapy (ADT) using propensity-score matched (PSM) data. This retrospective study queried two data registries collecting patient data from 1991 to present. 633 patients with UIR prostate cancer treated with HDR BT alone, HDR BT+EBRT or HDR+EBRT+ADT were included. HDR BT patients received 42-45Gy/6 fractions (fx) or 27 Gy/2 fx. For HDR BT+EBRT, the HDR dose was 20-24 Gy/2 fx, 24 Gy/4 fx, or 15 Gy/1 fx. EBRT patients received 45 Gy/25 fx to the prostate +/- pelvic nodes. GU/GI toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Time-to-event analyses were carried out to evaluate the relationship between treatments and five primary endpoints of interest: freedom from biochemical recurrence (FFBC), freedom from distant metastasis (FFDM), freedom from local failure (FFLF), cancer specific survival (CSS), and overall survival (OS) at 5 years. PSM was performed with one-to-n matching. Logistic regression was used to estimate the respective propensity scores. The five potential confounders identified were T-stage, Gleason score, pre-treatment PSA, age, and percent positive cores. Balance was checked using the standardized mean difference of covariates. Univariate and multivariate analyses were conducted on the matched data. Toxicity analysis was performed via association between a change in pre- and post-treatment GU/GI toxicity status and the treatment group, as well as incidence of post-treatment severe GI/GU toxicity (grade 3 or higher) and the treatment group. Univariate analysis with Kaplan-Meier method and log rank test comparison between the three cohorts demonstrated no significant difference in all survival outcomes FFBC, FFDM, FFLF, CSS, OS (p = 0.15, 0.19, 0.29, 0.57, 0.28, respectively). Multivariate analysis with Cox proportional hazard regression showed no differences in HR for FFBC and OS (p = 0.95, 0.11) with addition of EBRT, or with EBRT+ADT (p = 0.17, 0.24); no fit was obtainable for FFDM, CSS, FFLF. Toxicities between the three cohorts were not significantly different when comparing post-treatment and baseline GI/GU symptoms (p = 0.53/1). No Grade 2 or 3 GI toxicities were identified, while 8%/1% HDR patients, 10%/1% HDR+EBRT patients, and 12%/2% HDR+EBRT+ADT patients experienced Grade 2/3 GU toxicities. The incidence of grade 3 or higher GU toxicities between the three groups was not significantly different (p = 0.91). This propensity-score matched study demonstrates the feasibility of HDR BT alone for effective treatment of UIR prostate cancer when compared to HDR+EBRT or HDR+EBRT+ADT, while potentially minimizing the added toxicities of EBRT and the undesirable side effect profile of ADT.

PP04 Presentation Time: 9:47 AM: Outcomes of Patients with Unfavorable Intermediate Risk Prostate Cancer Treated with External Beam Radiotherapy and Brachytherapy with or without Androgen Deprivation Therapy

PP04 Presentation Time: 9:47 AM: Outcomes of Patients with Unfavorable Intermediate Risk Prostate Cancer Treated with External Beam Radiotherapy and Brachytherapy with or without Androgen Deprivation Therapy

PO65: A Potential Role for HDR Brachytherapy Alone in the Treatment of Unfavorable Intermediate Risk Prostate Cancer

PO65: A Potential Role for HDR Brachytherapy Alone in the Treatment of Unfavorable Intermediate Risk Prostate Cancer

Combined radiotherapy and hormone therapy in unfavorable intermediate risk prostate cancer

Background. Currently, the group of intermediate risk prostate cancer (PC) includes 2 subgroups - favorable and unfavorable intermediate risk according to the National Comprehensive Cancer Network (NCCN) classification. The optimal scope of therapy is not defined for the unfavorable intermediate risk subgroup. In particular, the need for and duration of hormone therapy (HT) during combined radiotherapy (CRT) have not yet been determined.Aim. To perform a comparative analysis of the efficacy and toxicity of CRT in patients with unfavorable intermediate risk treated with and without HT.Materials and methods. Eighty-four (84) patients with unfavorable intermediate risk PC were treated with CRT at the clinic of the A.F. Tsyb Medical Radiological Research Center between May 2016 and December 2020. Patients were divided into two groups: external beam radiation therapy + brachytherapy (n = 40) and external beam radiation therapy + brachytherapy + HT (n = 44). Conformal external beam radiation therapy was delivered with conventional fractionation to a total dose of 44-46 Gy and the 192Ir high-dose rate brachytherapy was delivered with a single fraction of 15 Gy. Median duration of HT consisting of gonadotropin-releasing hormone agonist was 6 months. Median age was 65.2 years (range: 49-80 years). Median follow-up was 58.1 months (range: 18.6-83.7 months).Results. With a median follow-up of 4.8 years, progression-free survival was 95 % and 97.6 % in the external beam radiation therapy + brachytherapy group and external beam radiation therapy + brachytherapy + HT group, respectively (p = 0.578). The break between treatment stages of more than 28 days was associated with a statistically significant increase in the risk of PC recurrence (p = 0.007). Overall survival for the external beam radiation therapy + brachytherapy group versus external beam radiation therapy + brachytherapy + HT group was 97.5 and 93.2 % (p = 0.376), respectively.Late genitourinary toxicity was grade I in 8 (9.5 %) patients and grade II in 1 (1.2 %) patient. Urethral stricture developed in 3 (3.6 %) patients. Late gastrointestinal toxicity was grade I in 7 (8.3 %) patients and grade II in 1 (1.2 %) patient. There were no statistically significant differences in the incidence of late complications between groups with and without HT. There was a statistically significant (p = 0.049) effect of prostate volume on the incidence of late radiation proctitis.Conclusion. There were no statistically significant differences in progression-free survival and overall survival in patients with unfavorable intermediate risk PC who received external beam radiation therapy + brachytherapy with or without HT. The incidence and severity of adverse events were acceptable and allowed patients with PC to maintain high quality of life.

Late Toxicity of Moderately Hypofractionated Intensity-Modulated Proton Therapy Treating the Prostate and Pelvic Lymph Nodes for High-Risk Prostate Cancer

To evaluate late gastrointestinal (GI) and genitourinary (GU) toxicity of moderately hypofractionated intensity modulated proton therapy (IMPT) targeting the prostate and pelvic lymph nodes. A target accrual of 56 patients with high-risk or unfavorable intermediate risk prostate cancer were enrolled into a prospective study (ClinicalTrials.gov: NCT02874014)of moderately hypofractionated IMPT. IMPT with pencil beam scanning was used to deliver 6750 and 4500 cGy relative biological effectiveness in 25 dailyfractions simultaneously to the prostate and pelvic lymph nodes, respectively. All received androgen deprivation therapy. Late GI and GU toxicity was prospectively assessed using Common Terminology Criteria for Adverse Events version 4.0, at baseline, weekly during radiation therapy, 3-month postradiation therapy, and then every 6 months. Actuarial rates of late GI and GU toxicity were estimated using Kaplan-Meier method. Median age was 75.5 years. Fifty-four patientswere available for late toxicity evaluation. Median follow-up was 43.9 months (range, 16-66). The actuarial rate of late grade ≥2 GI toxicity at both 2 and 3 years was 7.4% (95% confidence interval [CI], 0.2%-14.2%). The actuarial rate of late grade 3 GI toxicity at both 2 and 3 years was 1.9% (95% CI, 0%-5.4%). One patient experienced grade 3 GI toxicity with proctitis. The actuarial rate of late grade ≥2 GU toxicity was 20.5% (95% CI, 8.9%-30.6%) at 2 years, and 29.2 % (95% CI, 15.5%-40.7%) at 3 years. None had grade 3 GU toxicity. The presence of baseline GU symptoms was associated with a higher likelihood of experiencing late grade 2 GU toxicity. A moderately hypofractionated IMPT targeting the prostate and regional pelvic lymph nodes was generally well tolerated. Patients with pre-existing GU symptoms had a higher rate of late grade 2 GU toxicity. A phase 3 study is needed to assess any therapeutic gain of IMPT, in comparison with photon-based radiation therapy.

Late Gastrointestinal and Genitourinary Toxicities of a Moderately Hypofractionated Regimen of Intensity-Modulated Proton Therapy Targeting the Prostate/Seminal Vesicles and Pelvic Lymph Nodes for High Risk or Unfavorable Intermediate Risk Prostate Cancer

<h3>Purpose/Objective(s)</h3> To assess late gastrointestinal (GI) and genitourinary (GU) toxicities of intensity-modulated proton therapy (IMPT) targeting the prostate/seminal vesicles and regional pelvic lymph nodes for high risk (HR) or unfavorable intermediate risk (UIR) prostate cancer (Pca). <h3>Materials/Methods</h3> A prospective study (ClinicalTrials.gov: NCTXXX) to evaluate a moderately hypofractionated regimen of IMPT for HR-Pca or UIR-Pca accrued a target sample size of 55 patients. The prostate/seminal vesicles and pelvic lymph nodes were treated simultaneously with 67.5 Gy (2.7 Gy/fraction) and 45 Gy (1.8 Gy/fraction), respectively, in 25 fractions over 5 weeks. IMPT plan was prepared with pre-defined dose-volume histogram objectives for target volumes and organs at risk. All received androgen deprivation therapy (ADT). GI and GU toxicities were prospectively assessed, using the CTCAEv.4, at baseline (before IMPT); 3-, 6-, and 12-month post-RT and then every 6 months thereafter. Late toxicity was defined as toxicity persisting for > 3 months, or developing > 3 months post-RT. Late GI and GU toxicity rates were computed using Kaplan-Meier estimates, and log-rank tests were utilized for comparisons of time-to-event distributions. <h3>Results</h3> Median age was 75 years (range: 55-87). Median PSA was 10.5 ng/mL (range: 0.65 -97.3). Fifty-three patients had HR-Pca; 2 had UIR-Pca. Median duration of ADT was 18 months. Fifty-four patients were available for late toxicity assessment. Median follow-up was 46 months (range: 16-66). 29% and 6% experienced late grade 1 and 2 GI toxicity, respectively. One patient (2%) had late grade 3 GI toxicity (proctitis). The actuarial rate of late grade ≥ 2 GI toxicity was 7% (95% CI: 0.2-14%) at both 2 and 3 years. The actuarial rate of late grade 3 GI toxicity was 2% (95% CI: 0-5%) at both 2 and 3 years. 76% and 24% experienced late grade 1 and 2 GU toxicity, respectively. None had late grade ≥ 3 GU toxicity. The actuarial rate of late grade 2 GU toxicity was 21% (95% CI: 9-31%) at 2 years, and 29% (95% CI: 15-40%) at 3 years. None had late grade ≥ 4 GI or GU toxicity. The presence of baseline GU symptom was associated with a greater likelihood of experiencing late grade 2 GU toxicity. Of 44 patients with baseline GU symptoms, late grade 2 GU toxicity rate at 3 years was 36% (95%: 19-49%), compared to 0% among 10 patients with no baseline GU symptoms (p=0.02). <h3>Conclusion</h3> A moderately hypofractionated regimen of IMPT targeting prostate/seminal vesicles and pelvic lymph nodes for HR-Pca or UIR-Pca yielded very acceptable late GI and GU toxicity.

PSOR9 Presentation Time: 12:10 PM: Utilization of Brachytherapy Boost in Men with Unfavorable Intermediate Risk Prostate Cancer Treated with Radiation Plus Androgen Deprivation Therapy

<h3>Purpose</h3> Randomized data has shown a lower risk of recurrence with the addition of a brachytherapy (BT) boost in men with intermediate- and high-risk prostate cancer treated with external beam radiotherapy (EBRT) and concomitant androgen deprivation therapy (ADT). The inclusion of ADT with BT-based dose escalation is controversial, and professional guidelines support adding or excluding ADT for men with unfavorable intermediate risk prostate cancer treated with EBRT plus a BT boost. However, inclusion of ADT in men with intermediate risk prostate cancer may become more routine after results from RTOG 0815, and its impact on BT utilization in this population is unclear. Herein, we investigate the landscape of BT boost utilization in men with unfavorable intermediate risk prostate treated with EBRT and ADT in the United States. <h3>Materials and Methods</h3> Men ≥ 18 years diagnosed with clinical stage T1-2N0M0, PSA < 20, and Gleason grade group 3 prostate cancer between 2004-2017 were analyzed from the National Cancer Database. Those missing risk-stratification or treatment data were excluded. Eligible patients were grouped into the following cohorts based on primary radiation treatment modality: (i) EBRT alone or (ii) EBRT plus BT boost. EBRT monotherapy group received conventionally fractionated (1.8-2.0 Gy per fraction) ≥ 74 Gy or moderately hypofractionated (2.5-3.0 Gy per fraction) ≥ 60 Gy. EBRT plus BT boost group received conventionally fractionated ≥ 45 Gy or moderately hypofractionated ≥ 37.5 Gy, and either LDR or HDR BT. All patients received concomitant ADT. Cochran-Armitage was used to evaluate radiation modality treatment trends over time, and multivariable logistic regression was used to identify sociodemographic predictors of treatment. <h3>Results</h3> Among the eligible cohort, 46,490 (82%) were treated with EBRT alone and 10,236 (18%) were treated with EBRT plus BT boost. Median (range) age was 70 years (38-90). Between 2004 to 2017, there was a significant decline in annual use of a BT boost, from 24.5% in 2004 to 16.4% in 2017 (p<0.001). On MVA, Black race (adjusted OR 0.85, 95% CI 0.79-0.90, P<.0001), Medicaid insurance (aOR 0.67, 95% CI 0.57-0.78, P<.0001), and Charlson-Deyo comorbidity index > 1 (aOR 0.78, 95% CI 0.61-0.99, P=0.04) were associated with decreased odds of receiving a BT boost. Private insurance (aOR 1.11, 95% CI 1.05-1.18, P=.001), treatment at an academic institution (aOR 1.25, 95% CI 1.12-1.39, p<.0001), and Charlson-Deyo comorbidity index 0 (aOR 1.07, 95% CI 1.00-1.15, P=.04) were associated with increased odds of receiving a BT boost. <h3>Conclusions</h3> For men with unfavorable intermediate risk prostate cancer, utilization of a BT boost has significantly declined in the United States over the past two decades. Black and uninsured men have been at particularly high risk of undertreatment. Future studies aimed at identifying which men with intermediate-risk prostate cancer (e.g. based on genomic classifier or magnetic resonance imaging) derive the greatest oncologic benefit from a BT boost with EBRT and ADT is warranted to appropriately identify those who may be at risk of undertreatment with its exclusion. Additionally, future initiatives are needed to close the disparity gap in access and/or delivery of this efficacious treatment for Black and uninsured men, an overall undertreated population.

Quantitative Relaxometry for Target Localization and Response Assessment in Ultra-Hypofractionated MR-Guided Radiotherapy to the Prostate and DIL

<h3>Purpose/Objective(s)</h3> MR-guided systems, such as hybrid MR-Linacs, provide a novel platform for the acquisition and development of image-based biomarkers that can provide crucial information during daily online plan adaptation. Relaxometry has been shown to be sensitive to changes in tissue composition or function during radiotherapy. We investigate the added value of longitudinal relaxometry for target localization and response assessment. <h3>Materials/Methods</h3> The study included 42 unfavorable intermediate risk prostate patients undergoing ultra-hypofractionated MR-guided adaptive therapy to the prostate and seminal vesicles CTV with an integrated boost to the dominant intraprostatic lesion (DIL). The prescription was 800/900 cGy x 5 fractions, every other day. The longitudinal (T1) and transverse (T2) relaxation times were measured in the MR-Linac. T1 maps were acquired using the variable flip-angle method: TR/TE=20/2.3 ms, FA={4°, 22°}, FOV=320 × 320 × 200 mm, voxel = 0.7 × 0.7 × 3 mm³, scan time = 1.5 min. T2 maps were acquired using the multi-echo spin-echo method: TR/TE/ΔTE = 4000/22/11 ms, 8 echoes, FOV = 320 × 320 × 100 mm, voxel = 0.5 × 0.5 × 3 mm³, scan time = 5.5 min. The bias and reproducibility of T1/T2 mapping was assessed over the course of eight weeks using a NIST-traceable phantom. Longitudinal phantom measurements were also used to establish baseline values for T1/T2. The analysis was implemented in the Computational Environment for Radiotherapy Research. Daily T1 and T2 maps of prostate patients were rigidly registered to the pre-beam online-planning T2w images and T1/T2 values were analyzed within the CTV/DIL contours. <h3>Results</h3> The median bias with respect to nominal values for T1, T2 was -1.1%, 3.4%. When compared to baseline, the median bias for T1, T2 was 0.6%, 0.1% and the coefficient of variation was 2.1%, 0.9%, respectively. Maximum translation and rotation corrections within the T1/T2 maps were 1.9±0.3mm and 0.9°±0.2°. Across all patients and fractions, T1_CTV=1766±150ms, T1_DIL=1559±245ms, T2_CTV=127±19ms, T2_DIL=111±19ms. T1 and T2 were significantly longer in the CTV. Variations over fraction number are shown in Table 1. Linear regression showed there is a significant increase of mean T1 in the DIL (p=0.05) and CTV (p=0.05). The increase in T1 from fraction 1 to fraction 5 was 12.3% and 6.3% in DIL and CTV, respectively. The trend for T2 was not significant for either DIL or CTV. <h3>Conclusion</h3> T1 and T2 quantitative relaxometry is a surrogate measure of unbound water content and motility and shows the potential to serve as a predictor for changes in the local tumor microenvironment during MR-guided adaptive radiotherapy.

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&lt;.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.

MP64-05 A NEW MODEL FOR PREDICTION OF HIGH-RISK FEATURES AMONG UNFAVORABLE INTERMEDIATE RISK PROSTATE CANCER PATIENTS

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy VI (MP64)1 Sep 2021MP64-05 A NEW MODEL FOR PREDICTION OF HIGH-RISK FEATURES AMONG UNFAVORABLE INTERMEDIATE RISK PROSTATE CANCER PATIENTS Lara Franziska Stolzenbach, Luigi Nocera, Claudia Collà-Ruvolo, Mike Wenzel, Zhe Tian, Alberto Briganti, Sophie Knipper, Tobias Maurer, Derya Tilki, Hartwig Huland, Markus Graefen, and Pierre I. Karakiewicz Lara Franziska StolzenbachLara Franziska Stolzenbach More articles by this author , Luigi NoceraLuigi Nocera More articles by this author , Claudia Collà-RuvoloClaudia Collà-Ruvolo More articles by this author , Mike WenzelMike Wenzel More articles by this author , Zhe TianZhe Tian More articles by this author , Alberto BrigantiAlberto Briganti More articles by this author , Sophie KnipperSophie Knipper More articles by this author , Tobias MaurerTobias Maurer More articles by this author , Derya TilkiDerya Tilki More articles by this author , Hartwig HulandHartwig Huland More articles by this author , Markus GraefenMarkus Graefen More articles by this author , and Pierre I. KarakiewiczPierre I. Karakiewicz More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002104.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Under current guidelines, radical prostatectomies (RP) for unfavorable intermediate risk prostate cancer (UIR PCa) patients are deferred . However, high risk criteria (pT3-4/pN1 stage and/or GGG IV-V) will be present in some unfavorable intermediate risk prostate cancer (UIR PCa) patients. These individuals should be prioritized for definitive therapy. We attempted to identify them. METHODS: A total of 2,024 UIR PCa patients treated with radical prostatectomy were abstracted from an institutional database (2000-2018). Multivariable logistic regression models predicting high risk criteria (pT3-4/pN1 stage and/or GGG IV-V) in IR PCa were developed, validated and directly compared with NCCN IR PCa stratification. RESULTS: All 2,024 patients were randomly divided between development (n=1,012, 50.0%) and validation cohorts (n=1,012, 50.0%). The development cohort was used to fit a new model (PSA level, clinical T stage, biopsy Gleason Grade Group (GGG), cumulative tumor length in available biopsy cores [all p<0.001]) to predict high-risk criteria according to RP pathology, using. At RP, the rates of pT3-4/pN1, GGG IV-V and of both were 52.2, 3.7 and 55.9%, respectively. Within the validation cohort, the new model outperformed any combination of NCCN UIR PCa criteria in accuracy (70.1 vs 63.0%), calibration and decision curve analyses. The new model derived probability cutoff of 50.0% for presence of pT3-4/pN1/GGG IV-V identified 317 (31.1%) of 1,012 patients, in whom the rate of pT3-4/pN1/GGG IV-V was 65.9%, instead of average 44.6%. CONCLUSIONS: We developed a new model that can accurately identify a subset of NCCN UIR PCa patients with significantly higher proportion of high-risk criteria (pT3-4/pN1 stage and/or GGG IV-V). These individuals should be prioritized for definitive therapy during COVID-19-pandemic. Source of Funding: There was no external financial support for this study. The authors declare that they have no conflict of interest © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1111-e1111 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Lara Franziska Stolzenbach More articles by this author Luigi Nocera More articles by this author Claudia Collà-Ruvolo More articles by this author Mike Wenzel More articles by this author Zhe Tian More articles by this author Alberto Briganti More articles by this author Sophie Knipper More articles by this author Tobias Maurer More articles by this author Derya Tilki More articles by this author Hartwig Huland More articles by this author Markus Graefen More articles by this author Pierre I. Karakiewicz 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.

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.

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.

PP10 Presentation Time: 11:40 AM: Comparison of HDR Brachytherapy Alone to HDR Brachytherapy as a Boost for Treatment of Unfavorable Intermediate Risk Prostate Cancer

PP10 Presentation Time: 11:40 AM: Comparison of HDR Brachytherapy Alone to HDR Brachytherapy as a Boost for Treatment of Unfavorable Intermediate Risk Prostate Cancer

PP10 Presentation Time: 11:40 AM: Comparison of HDR Brachytherapy Alone to HDR Brachytherapy as a Boost for Treatment of Unfavorable Intermediate Risk Prostate Cancer

PP10 Presentation Time: 11:40 AM: Comparison of HDR Brachytherapy Alone to HDR Brachytherapy as a Boost for Treatment of Unfavorable Intermediate Risk Prostate Cancer

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.

Does ADT benefit unfavourable intermediate risk prostate cancer patients treated with brachytherapy boost and external beam radiotherapy? A propensity-score matched analysis

PurposeTo investigate the role of androgen deprivation therapy (ADT) in unfavorable intermediate risk (UIR) prostate cancer patients treated with high-dose rate (HDR) brachytherapy (BT) boost. Material and methodsData from 326 consecutive NCCN UIR prostate cancer patients treated in a single institution from 2009 to 2016 with 15 Gy HDR-BT boost plus 37.5 Gy external beam radiotherapy (EBRT) in 15 fractions to prostate and proximal seminal vesicles were retrospectively collected. Baseline information was collected and patients receiving vs. not receiving ADT were matched using a propensity-score model. Primary endpoint was biochemical-failure-free survival (BFFS). Kaplan–Meier estimates and stratified log-rank tests (adjusting for matched design) were used to compare BFFS, castration-resistance (CRFS) and metastasis free survival (MFS) outcomes between both groups. ResultsA total of 326 patients were included in the analysis of which 52 ADT patients were matched to 104 non-ADT patients in a 1:2 ratio. Median follow-up was 3.4 years and 5.5 years for ADT and non-ADT respectively. No significant baseline differences were observed. ADT was used for a median total time of 6 months (interquartile range [IQR]: 4–6) and delivered a median time of 2.7 months (IQR: 1.7–4.3) prior to HDR-BT. BFFS was significantly improved in the ADT group (stratified log-rank: p = 0.043) with 3-year and 6-year BFFS of 98% and 90% for the ADT group and 92% and 82% for the non-ADT group, respectively. No significant differences were detected for CRFS or MFS. ConclusionShort-term ADT increased BFFS in UIR prostate cancer patients treated with HDR-BT boost plus EBRT.

The 17-Gene Genomic Prostate Score Test as a Predictor of Outcomes in Men with Unfavorable Intermediate Risk Prostate Cancer

To evaluate the association of the Genomic Prostate Score (GPS) assay result with biochemical recurrence (BCR), distant metastases (DM), and prostate-specific death (PCD) in unfavorable intermediate (UFI) risk prostate cancer patients. The GPS assay is used to help guide management decisions for newly diagnosed low and favorable intermediate (FI) risk disease. GPS results from 2 studies (Center for Prostate Disease Research [CPDR]; Kaiser Permanente Northern California [KPNC]) in men treated with radical prostatectomy were analyzed to determine associations of the GPS result with BCR, DM, and PCD in UFI risk disease. Analyses included 299 intermediate risk prostate patients, 175 of whom had UFI risk disease (KPNC=103; CPDR=72). The GPS result as a dichotomous value (≤40 vs >40) was a significant predictor of BCR in UFI patients in multivariate analyses (hazard ratio [HR] 6.0; 95% confidence interval [CI] 2.0-22.4; P=.0035; CPDR). The GPS result was a strong predictor of all 3 endpoints in multivariate analyses (BCR HR 7.1; 95% CI 5.7-8.8; P < .0001; DM HR 5.4; 95% CI 3.8-7.8; P < .0001; PCD HR 3.4; 95% CI 1.5-8.9; P=.006; KPNC). UFI patients with GPS >40 had outcomes consistent with high-risk disease, whereas UFI patients with GPS ≤40 had outcomes similar to FI risk patients (CPDR/KPNC). The GPS result was a strong independent predictor of BCR, DM, and PCD in intermediate risk prostate cancer. UFI patients with GPS >40 have a poor prognosis and may benefit from additional therapeutic options.