Very High-risk Prostate Cancer Research Articles

Adaptive ultra-hypofractionated whole-pelvic radiotherapy in high-risk and very high-risk prostate cancer on 1.5-Tesla MR-Linac: Estimated delivered dose and early toxicity results.

Magnetic resonance (MR)-guided ultra-hypofractionated radiotherapy with whole-pelvic irradiation (UHF-WPRT) is a novel approach to radiotherapy for patients with high-risk (HR) and very high-risk (VHR) prostate cancer (PCa). However, the inherent complexity of adaptive UHF-WPRT might inevitably result in longer on-couch time. We aimed to estimate the delivered dose, study the feasibility and safety of adaptive UHF-WPRT on a 1.5-Tesla MR-Linac. Ten patients with clinical stage T3a-4N0-1M0-1c PCa, who consecutively received UHF-WPRT, were enrolled prospectively. The contours of the target and organ-at-risks on the position verification-MR (PV-MR), beam-on 3D-MR(Bn-MR), and post-MR (after radiotherapy delivery) were derived from the pre-MR data by deformable image registration. The physician then manually adjusted them, and dose recalculation was performed accordingly. GraphPad Prism 9 (GraphPad Prism Software Inc.) was utilized for conducting statistical analyses. In total, we collected 188 MR scans (50 pre-MR, 50 PV-MR, 44 Bn-MR, and 44 post-MR scans). With median 59 min, the mean prostate clinical target volume (CTV)-V100% was 98.59% ± 2.74%, and the mean pelvic CTVp-V100% relative percentages of all scans was 99.60% ± 1.18%. The median V29 Gy change in the rectal wall was -2% (-18% to 20%). With a median follow-up of 9 months, no patient had acute Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or more severe genitourinary (GU) or gastrointestinal (GI) toxicities (0%). UHF-RT to the prostate and the whole pelvis with concomitant boost to positive nodes using an Adapt-To-Shape (ATS) workflow was technically feasible for patients with HR and VHR PCa, presenting only mild GU and GI toxicities. The estimated target dose during the beam-on phase was clinically acceptable based on the 3D-MR-based dosimetry analysis. Chinese Clinical Trial Registry ChiCTR2000033382.

Prospective results for 5-year survival and toxicity of moderately hypofractionated radiotherapy with simultaneous integrated boost (SIB) in (very) high-risk prostate cancer

PurposeHigh-risk (HR) prostate cancer patients usually receive high-dose radiotherapy (RT) using a two-phase sequential technique, but data on a simultaneous integrated boost (SIB) technique are lacking. We prospectively evaluated the long-term results of urinary (GU) and digestive (GI) toxicity and survival data for high-dose RT using a SIB technique in HR and very high-risk (VHR) prostate cancer. MethodsPatients were treated using an SIB technique in 34 fractions, at a dose of 54.4 Gy to the pelvis and seminal vesicles and 74.8 Gy to the prostate, combined with 36 months of androgen-depriving therapy in a prospective multicenter study. Acute and late GU and GI toxicity data were collected. Overall survival (OS), biochemical-relapse-free survival (bRFS), loco-regional-relapse-free survival (LRRFS), metastasis-free-survival (MFS) and disease-free-survival (DFS) were assessed. ResultsWe recruited 114 patients. After a median follow-up of 62 months, very few patients experienced acute (M0-M3) (G3-4 GU = 3.7 %; G3-4 GI = 0.9 %) or late (M6-M60) severe toxicity (G3-4 GU = 5.6 %; G3-4 GI = 2.8 %). The occurrence of acute G2 + GU or GI toxicity was significantly related to the consequential late G2 + toxicity (p < 0.01 for both GU and GI). Medians of OS, bRFS, LRRFS, MFS and DFS were not reached. At 60 months, OS, bRFS, LRRFS, MFS and DFS were 88.2 % [82.1; 94.7], 86.0 % [79.4 %;93.2 %], 95.8 % [91.8 %;99.9 %], 87.2 % [80.9 %;94.0 %] and 84.1 % [77.2 %;91.6 %] respectively. ConclusionSIB RT at a dose of 54.4 Gy to the pelvis and 74.8 Gy to the prostate is feasible, leading to satisfying tumor control and reasonable toxicity in HR and VHR prostate cancer.

Adaptive Ultra-Hypofractionated Whole-Pelvic Radiotherapy in High-Risk and Very High-Risk Prostate Cancer on 1.5-1.5 MR Linac: The Estimated Delivered Dose and Early Toxicity Results

To study the feasibility and safety for patients with high-risk (HR) and very high-risk (VHR) prostate cancer treated with adaptive ultra-hypofractionated whole-pelvic radiotherapy (UHF-WPRT) on 1.5 magnetic resonance (MR)-Linac. Sevenpatients with clinical stage T3a-4N0-1M0-1c consecutively treated with UHF-WPRT on a 1.5-T MR-Linac were recruited prospectively in a phase II trial (NCT05183074, ChiCTR2000033382). A 36.25 Gy dose in five fractions was delivered every other day with a boost of 40 Gy to the whole prostate, as well as 25 Gy to whole pelvic nodal area with a concomitant boost of 35 Gy to metastatic regional nodes. To estimate the delivered dose, we collected data by 3D-MR for the following stages: pre-MR, position verification-MR (PV-MR) in the Adapt-To-Shape (ATS) workflow, and 3D-MR during the beam-on phase (Bn-MR) and at the end of RT (post-MR). The target and organ-at-risk contours in the PV-MR, Bn-MR, and post-MR stages were projected from the pre-MR data by deformable image registration and manually adapted by the physician, followed by dose recalculation for the ATS plan. The cumulative acute genitourinary (GU) and gastrointestinal (GI) toxicities were evaluated as per NCI-CTCAE 5.0 criteria. The primary endpoints were acute ≥grade 3 genitourinary (GU) and gastrointestinal (GI) toxicities during the first 3 months. Overall, 133 MR scans were collected (35 pre-MR, 35 PV-MR, 31 Bn-MR and 32 post-MR scans). With a median on-couch time of 61 minutes, the mean prostate and pelvic planning target volume (PTV)-V95% of all scans was 96.98 ± 3.06% and 96.44 ± 2.85%, respectively. The corresponding mean prostate clinical target volume (CTV)-V100% was 99.89 ± 0.32%, 98.71 ± 1.90%, 97.77 ± 2.89%, and 98.56 ± 1.72%, and the mean pelvic CTV-V100% was 97.57% ± 3.70%, 96.54 ± 3.80%, 95.43 ± 4.31%, and 94.39 ± 4.47% on pre-MR, PV-MR, Bn-MR and post-MR scans, respectively. For the 4 patients with positive nodes, the mean V100% of metastatic regional nodes was 99.89 ± 0.81%. The median V29 Gy change in the rectal wall was -1% (-18%-20%). The V29 Gy of the rectal wall increased by >15% was observed in one scan. A slight increase in the high dose of bladder wall was noted due to gradual bladder growth during the workflow. With median follow-up time of 7.3 (4.6-12.2) months, all patients were followed-up for more than 3 months. No patient was observed with acute CTCAE grade 2 or more severe GU or GI toxicities (0%). UHF-RT to prostate and pelvic with ATS workflow is well tolerated by patients with HR and VHR prostate cancer, with only mild GU and GI toxicities. The 3D-MR-based dosimetry analysis demonstrated clinically acceptable estimated dose coverage of target volumes during the beam-on period.

Radiation Facility Volume and Survival for Men With Very High-Risk Prostate Cancer Treated with Radiation and Androgen Deprivation Therapy

Very high-risk (VHR) prostate cancer is an aggressive substratum of high-risk prostate cancer, characterized by high prostate-specific antigen levels, high Gleason score, and/or advanced T category. Contemporary management paradigms involve advanced molecular imaging and multimodal treatment with intensified prostate-directed or systemic treatment-resources more readily available at high-volume centers. To examine radiation facility case volume and overall survival (OS) in men with VHR prostate cancer. A retrospective cohort study was performed from November 11, 2022, to March 4, 2023, analyzing data from US facilities reporting to the National Cancer Database. Patients included men diagnosed with nonmetastatic VHR prostate cancer by National Comprehensive Cancer Network criteria (clinical T3b-T4 category, primary Gleason pattern 5, >4 cores with grade group 4-5, and/or 2-3 high-risk features) and treated with curative-intent radiotherapy and androgen deprivation therapy between January 1, 2004, to December 31, 2016. Treatment at high- vs low-average cumulative facility volume (ACFV), defined as the total number of prostate radiotherapy cases at an individual patient's treatment facility from 2004 until the year of their diagnosis. The nonlinear association between a continuous ACFV and OS was examined through a Martingale residual plot; an optimal ACFV cutoff was identified that maximized the separation between high vs low ACFV via a bias-adjusted log rank test. Overall survival was assessed between high vs low ACFV using Kaplan-Meier analysis with and without inverse probability score weighted adjustment and multivariable Cox proportional hazards. A total of 25 219 men (median age, 71 [IQR, 64-76] years; 78.7% White) with VHR prostate cancer were identified, 6438 (25.5%) of whom were treated at high ACFV facilities. Median follow-up was 57.4 (95% CI, 56.7-58.1) months. Median OS for patients treated at high ACFV centers was 123.4 (95% CI, 116.6-127.4) months vs 109.0 (95% CI, 106.5-111.2) months at low ACFV centers (P < .001). On multivariable analysis, treatment at a high ACFV center was associated with lower risk of death (hazard ratio, 0.89; 95% CI, 0.84-0.95; P < .001). These results were also significant after inverse probability score weighted-based adjustment. In this cohort study of patients with VHR prostate cancer who underwent definitive radiotherapy and androgen deprivation therapy, facility case volume was independently associated with longer OS. Further studies are needed to identify which factors unique to high-volume centers may be responsible for this benefit.

Transcriptomic Heterogeneity in High-risk Prostate Cancer and Implications for Extraprostatic Disease at Presentation on Prostate-specific Membrane Antigen Positron Emission Tomography

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) has greater specificity and sensitivity for detection of extraprostatic prostate cancer (PCa) at presentation than conventional imaging. Although the long-term clinical significance of acting on these findings is unknown, it has been shown that the risk of upstaging is prognostic for long-term outcomes in men with high-risk (HR) or very high-risk (VHR) PCa. We evaluated the association between the risk of upstaging on PSMA PET and the Decipher genomic classifier score, a known prognostic biomarker in localized PCa that is being evaluated for its predictive ability to direct systemic therapy intensification. In a cohort of 4625 patients with HR or VHR PCa, the risk of upstaging on PSMA PET was significantly correlated with the Decipher score (p < 0.001). These results should be seen as hypothesis-generating and warrant further studies on the causal pathways linking PSMA findings, Decipher scores, extraprostatic disease, and long-term clinical outcomes. Patient summaryWe found significant correlation between the risk of having prostate cancer outside the prostate gland on a sensitive scan (based on prostate-specific membrane antigen [PSMA]) at initial staging and the Decipher genetic score. The results warrant further studies on the causal pathways between PSMA scan findings, Decipher scores, disease outside the prostate, and long-term outcomes.

Oncological outcomes with wide resection in robot-assisted radical prostatectomy as primary treatment for very high-risk prostate cancer.

357 Background: Patients with very high-risk prostate cancer (VHRPCa) have earlier biochemical recurrences (BCRs) and higher mortality rates. It remains unclear whether extended robot-assisted radical prostatectomy (eRARP) with intended wide resection can improve the outcomes of VHRPCa patients. We aimed to compare the oncological outcomes of eRARP versus standard RALP (sRARP) for primary treatment of VHRPCa. Methods: We retrospectively evaluated 168 patients classified by the National Comprehensive Cancer Network (NCCN) as very high-risk who were treated with RARP without neoadjuvant/adjuvant therapy between September 2011 and December 2020. eRARP was performed using the extra-fascial approach as reported by Gandaglia G et al. (Eur Urol. 71:249-256, 2017). We performed 1:1 propensity score matching to account for potential differences between eRARP and sRARP. Kaplan-Meier analysis and Cox regression models were used to test the effect of eRARP on the biochemical progression-free survival (bPFS). This observational study was approved by the Institutional Review Board. Results: There were 93 patients in the eRARP group and 75 in the sRARP group. The eRARP group had a worse clinical stage than the sRARP group ( p&lt; 0.001). Age, pretreatment prostate specific antigen (PSA), and pretreatment Gleason score were similar in the two groups. All patients in the eRARP group underwent pelvic lymph node dissection, compared with 89% in the sRARP group. The propensity-adjusted 3-year biochemical recurrence-free survival rates was 31.4% in the sRARP group and 67.4% in the eRARP group(p=0.001), respectively. The adjusted Cox regression analysis showed that the eRARP group had a significantly longer bPFS than the sRARP group (hazard ratio 0.415, p=0.0047). Conclusions: In patients with VHRPCa, eRARP was associated with a reduce risk of biochemical recurrence. These results suggest that eRARP may improve oncological outcomes in VHRPCa.

PSOR5 Presentation Time: 11:50 AM: Interstitial Hyperthermia and High Dose-Rate Brachytherapy Combined with Short-Term Androgen Deprivation Therapy and External-Beam Radiation in High- and Very High-Risk Prostate Cancer

<h3>Purpose</h3> Multimodality treatment of high- and very-high risk prostate cancer has evolved tremendously in recent years to incorporate long-term androgen deprivation therapy (ADT), external-beam radiation therapy (EBRT), and brachytherapy, resulting in improved biochemical progression-free survival (bPFS). However, outcomes remain imperfect, and many patients are unwilling or unable to tolerate long-term ADT use. Existing studies show that hyperthermia is a potent and well-tolerated radiosensitizer. We report the outcomes of patients treated with short-term ADT, EBRT, and high dose-rate (HDR) brachytherapy combined with interstitial hyperthermia. <h3>Materials and Methods</h3> In a single-institution, retrospective study, we reviewed all patients with high- or very high-risk prostate adenocarcinoma who began definitive treatment between December 2016 and March 2020 with up to six months of ADT, whole-pelvis EBRT, and a combination of HDR brachytherapy boost and interstitial hyperthermia. Our primary endpoint was bPFS based on the Phoenix definition (PSA nadir +2 ng/mL) calculated from time of ADT initiation. We also report data on type of failure, survival, and toxicity. <h3>Results</h3> 56 patients were reviewed, including 21 with high-risk and 35 with very high-risk prostate adenocarcinoma. Median age was 72 years (range 52-82 years). Median duration of ADT use was 4 months (range 0-6 months). All patients received whole-pelvis EBRT of 45Gy/25fx. 55 patients (98%) received a 5.4Gy/3fx EBRT boost to the prostate and seminal vesicles. All patients received two Iridium-192 HDR implants to further boost the prostate and seminal vesicles, with each implant separated by at least one week (median 2 weeks, range 1-6 weeks) and consisting of two fractions of 5.5Gy separated by five to seven hours, for a total of 22Gy/4fx. All patients received at least one interstitial hyperthermia treatment of at least 45 minutes in between fractions of the same implant. 50 patients (89%) received both planned hyperthermia treatments of at least 60 minutes each at a goal temperature of 42-43 degrees Celsius. Median duration of follow-up was 28 months for all patients, with 34 months for high-risk and 28 months for very-high risk disease. The estimated two/three-year bPFS-rates were 100%/100% for high-risk and 92.0%/87.7% for very high-risk disease. Figure 1 represents the Kaplan-Meier curve for bPFS. Of the three very high-risk patients who failed biochemically, one failed regionally at 25 months, and two failed distantly at 15 and 23 months. There were no local failures. Two patients with very-high risk disease have died, both of unrelated lung disease at nine and 13 months. Four patients stopped their hyperthermia treatment early due to intolerance, with one developing an acute perineal burn that fully healed three months later. There were otherwise no grade 3 or higher acute toxicities. Four patients (7%) developed late grade 3 toxicities, all genitourinary-related. <h3>Conclusions</h3> Multimodality treatment of prostate cancer with short-term ADT, EBRT, HDR brachytherapy, and interstitial hyperthermia is safe and well-tolerated. For patients with high-risk disease, it provides excellent biochemical control while sparing long-term use of ADT. Patients with very high-risk disease may benefit from long-term use of ADT and/or other forms of systemic therapy. Longer follow-up and prospective trials are needed to validate our findings.

External Beam Radiation Therapy With or Without Brachytherapy Boost in Men With Very-High-Risk Prostate Cancer: A Large Multicenter International Consortium Analysis

Very-high-risk (VHR) prostate cancer (PC) is an aggressive subgroup with high risk of distant disease progression. Systemic treatment intensification with abiraterone or docetaxel reduces PC-specific mortality (PCSM) and distant metastasis (DM) in men receiving external beam radiation therapy (EBRT) with androgen deprivation therapy (ADT). Whether prostate-directed treatment intensification with the addition of brachytherapy (BT) boost to EBRT with ADT improves outcomes in this group is unclear. This cohort study from 16 centers across 4 countries included men with VHR PC treated with either dose-escalated EBRT with ≥24 months of ADT or EBRT+BT boost with ≥12 months of ADT. VHR was defined by National Comprehensive Cancer Network (NCCN) criteria (clinical T3b-4, primary Gleason pattern 5, or ≥2 NCCN high-risk features), and results were corroborated in a subgroup of men who met Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trials inclusion criteria (≥2 of the following: clinical T3-4, Gleason 8-10, or PSA ≥40 ng/mL). PCSM and DM between EBRT and EBRT+BT were compared using inverse probability of treatment weight-adjusted Fine-Gray competing risk regression. Among the entire cohort, 270 underwent EBRT and 101 EBRT+BT. After a median follow-up of 7.8 years, 6.7% and 5.9% of men died of PC and 16.3% and 9.9% had DM after EBRT and EBRT+BT, respectively. There was no significant difference in PCSM (sHR, 1.47 [95% CI, 0.57-3.75]; P=.42) or DM (sHR, 0.72, [95% CI, 0.30-1.71]; P=.45) between EBRT+BT and EBRT. Results were similar within the STAMPEDE-defined VHR subgroup (PCSM: sHR, 1.67 [95% CI, 0.48-5.81]; P=.42; DM: sHR, 0.56 [95% CI, 0.15-2.04]; P=.38). In this VHR PC cohort, no difference in clinically meaningful outcomes was observed between EBRT alone with ≥24 months of ADT compared with EBRT+BT with ≥12 months of ADT. Comparative analyses in men treated with intensified systemic therapy are warranted.

OC-0611 HDR brachytherapy boost improves metastatic free survival in high and very-high risk prostate cancer

OC-0611 HDR brachytherapy boost improves metastatic free survival in high and very-high risk prostate cancer

125I Interstitial brachytherapy with or without androgen deprivation therapy among unfavorable-intermediate and high-risk prostate cancer

PURPOSE/OBJECTIVE(S)To determine if patients with unfavorable intermediate-risk (UIR), high-risk (HR), or very high-risk (VHR) prostate cancer (PCa) treated with 125I interstitial brachytherapy benefit from androgen deprivation therapy (ADT). MATERIALS/METHODSWe reviewed our institutional database of patients with UIR, HR, or VHR PCa, per 2018 NCCN risk classification, treated with definitive 125I interstitial brachytherapy with or without ADT from 1998−2017. Outcomes including biochemical failure (bF), distant metastases (DM), and overall survival (OS) were analyzed with the Kaplan-Meier method and Cox proportional hazards regression. PCa-specific mortality (PCSM) was analyzed with Fine-Gray competing-risk regression. RESULTSOf 1033 patients, 262 (25%) received ADT and 771 (75%) did not. Median ADT duration was 6 months. By risk group, 764 (74%) patients were UIR, 219 (21%) HR, and 50 (5%) VHR. ADT was more frequently given to HR (50%) and VHR (56%) patients compared to UIR (16%; p<0.001), to older patients (p<0.001), corresponding with increasing PSA (p<0.001) and Grade Group (p<0.001). Median follow-up was 4.9 years (0.3−17.6 years). On multivariable analysis accounting for risk group, age, and year of treatment, ADT was not associated with bF, DM, PCSM, or OS (p≥0.05 each). CONCLUSIONAmong patients with UIR, HR, and VHR PCa, the addition of ADT to 125I interstitial brachytherapy was not associated with improved outcomes, and no subgroup demonstrated benefit. Our findings do not support the use of ADT in combination with 125I interstitial brachytherapy. Prospective studies are required to elucidate the role of ADT for patients with UIR, HR, and VHR PCa treated with prostate brachytherapy.

Extended robot-assisted laparoscopic prostatectomy and extended pelvic lymph node dissection as a monotherapy in patients with very high-risk prostate cancer Patients.

BackgroundPatients with very‐high‐risk prostate cancer (VHRPCa) have earlier biochemical recurrences (BCRs) and higher mortality rates. It remains unknown whether extended robot‐assisted laparoscopic prostatectomy (eRALP) without neoadjuvant or adjuvant therapy can improve the outcomes of VHRPCa patients. We aimed to determine the feasibility and efficacy of eRALP as a form of monotherapy for VHRPCa.MethodsData from 76 men who were treated with eRALP without neoadjuvant/adjuvant therapy were analyzed. eRALP was performed using an extrafascial approach. Extended pelvic lymph node (LN) dissection (ePLND) included nodes above the external iliac axis, in the obturator fossa, and around the internal iliac artery up to the ureter. The outcome measures were BCR, treatment failure (defined as when the prostate‐specific antigen level did not decrease to <0.1 ng/ml postoperatively), and urinary continence (UC). Kaplan–Meier, logistic regression, and Cox proportional‐hazards model were used to analyze the data.ResultsThe median operative time was 246 min, and median blood loss was 50 ml. Twenty‐one patients experienced postoperative complications. Median follow‐up was 25.2 months; 19.7% of patients had treatment failure. Three‐year, BCR‐free survival rate was 62.0%. Castration‐resistant prostate cancer‐free survival rate was 86.1%. Overall survival was 100%. In 55 patients who had complete postoperative UC data, 47 patients (85.5%) recovered from their UC within 12 months. Clinical stage cT3b was an independent preoperative treatment failure predictor (p = 0.035), and node positivity was an independent BCR predictor (p = 0.037). The small sample size and retrospective nature limited the study.ConclusionsThis approach was safe and produced acceptable UC‐recovery rates. Preoperative seminal vesicle invasion is associated with treatment failure, and pathological LN metastases are associated with BCR. Therefore, our results may help informed decisions about neoadjuvant or adjuvant therapies in VHRPCa cases.PrecisExtended robot‐assisted laparoscopic prostatectomy and extended pelvic lymph node dissection without adjuvant therapy is safe and effective for some patients with very‐high‐risk prostate cancer. The clinical stage and node positivity status predicted monotherapy failure, which may indicate good adjuvant therapy candidate.

The Prognosis of Radical Prostatectomy, External Beam Radiotherapy plus Brachytherapy, and External Beam Radiotherapy Alone for Patients above 70 Years with Very High-Risk Prostate Cancer: A Population-Matched Study

Objective: The aim of this study was to evaluate the survival outcomes of radical prostatectomy (RP), external beam radiotherapy plus brachytherapy (EBRT + BT), and EBRT alone among elderly men (aged 70 years and above) with very high-risk (VHR) prostate cancer (PCa). Methods: We identified elderly men diagnosed with VHR PCa between 2004 and 2015 in the Surveillance, Epidemiology, and End Results database. The propensity score-matching method was adopted to balance the covariates and generate new cohorts. ­Kaplan-Meier and Cox analyses were conducted to build up survival curves and evaluate the overall survival (OS) and PCa-specific survival (PCSS) outcomes. Results: A total of 9,818 patients were identified. Of them, 5,839 were in the EBRT group, 725 in the EBRT + BT group, and 3,254 in the RP group. The survival curves of the overall cohort showed that RP was associated with the best OS, followed by EBRT + BT and EBRT (p < 0.001). As for the PCSS, RP shared similar outcomes with EBRT + BT (hazard ratio [HR]: 1.25 [0.93–1.69], p = 0.175). EBRT was associated with significantly worse PCSS than both RP (HR: 1.88, 95% confidence interval [95% CI] [1.64–2.15], p < 0.001) and EBRT + BT (HR: 1.48, 95% CI [1.19–1.85], p = 0.002). In the matched cohorts, RP presented better OS (HR: 1.41, 95% CI [1.07–1.86], p = 0.041) and similar PCSS with EBRT + BT (HR: 1.50, 95% CI [0.91–2.47], p = 0.12). RP was associated with significantly better OS and PCSS outcomes than EBRT alone (OS HR: 1.58, 95% CI [1.59–2.12], p < 0.001; PCSS HR: 2.08 [1.60–2.72], p < 0.001). EBRT + BT also had significantly better OS and PCSS outcomes than EBRT alone (OS HR: 1.33, 95% CI [1.11–1.60], p < 0.001; PCSS HR: 1.57 [1.13–2.19], p = 0.003). Conclusions: For patients above 70 years with VHR PCa, RP was associated with better OS and similar PCSS than EBRT + BT. Both RP and EBRT + BT have better OS and PCSS than EBRT alone.

Interim results of aasur: A single arm, multi-center phase 2 trial of apalutamide (A) + abiraterone acetate + prednisone (AA+P) + leuprolide with stereotactic ultra-hypofractionated radiation (UHRT) in very high risk (VHR), node negative (N0) prostate cancer (PCa).

5012 Background: Standard of care in VHR PCa is radiation therapy (RT) with 18-36 months (mos) of androgen-deprivation therapy (ADT). With this regimen, chronic ADT toxicity is significant and biochemical recurrence (BCR) frequent. We sought to improve tumor control and minimize toxicity with intensified short course ADT with dual androgen receptor signaling inhibitors (ARSI) and UHRT. Methods: 64 patients (pts) with VHR, N0 PCa were enrolled from 4 centers. VHR PCa was defined as Gleason score (GS) 9-10, &gt;4 cores of GS 8 disease, or 2 high-risk features (including rT3/T4 disease). Treatment (tx) involved 6 mos of A, AA+P, and leuprolide with prostate/seminal vesicle-directed RT (7.5-8 Gy x 5 fractions). The primary endpoint was BCR defined as nadir PSA + 2ng/mL. Biochemical recurrence-free survival (bRFS) is reported herein. Our hypothesized reduction in BCR from 25% to 10% at 3 years (yrs) required 53 pts to provide a power of 0.84 and an alpha of 0.03. Undetectable PSA was defined as &lt;0.10 ng/mL. Non-castrate testosterone (T) was a post-tx value &gt;150 ng/mL. All analyses were intention-to-treat. Toxicity and health-related quality of life measures were evaluated using CTCAEv4.0 and the EPIC-26 questionnaire. Results: Baseline characteristics are summarized in the Table; 63 of 64 pts completed protocol tx. Median time to nadir PSA from tx start was 2 mos (range, 1-9); 63 of 64 pts (98.4%) achieved an undetectable nadir PSA. Median time to post-tx, non-castrate T was 6.5 mos (range, 2.5-25.5). Median follow-up (f/u) for pts without BCR was 30 mos (range, 15-44). Seven pts had BCR; 2-yr bRFS was 95.0% (95% CI, 89.7-100); 3-yr bRFS was 89.7% (95 CI, 81.0-99.3). For the 57 pts without BCR, 56 (98.2%) had T &gt; 150ng/mL at last f/u; median PSA at last f/u was 0.10 ng/mL (IQR, &lt;0.10-0.30); of these, 40 (70.2%) pts had PSAs ≤ 0.20 ng/mL with 24 (42.1%) undetectable. Fifteen pts experienced transient Grade 3 toxicities: 12 (18.8%) with hypertension and 3 with rash (4.7%). EPIC-26 scores for a subset of pts (n=21) at baseline and 12 mos showed no significant decline in urinary or bowel domains; declines in sexual (-11.9) and hormone (-5.7) domains met significance. Conclusions: Compared to historic controls with the long course ADT, AASUR demonstrated impressive 3-yr bRFS, rapid T recovery, and limited toxicities; the safety profile of this regimen was consistent with the known AE profile of the ARSI and RT. This regimen warrants further, randomized evaluation. Funded by Janssen Pharmaceuticals. Managed by the Prostate Cancer Clinical Trials Consortium. Clinical trial information: NCT02772588. [Table: see text]

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.

125I Interstitial Brachytherapy with or without Androgen Deprivation Therapy among Unfavorable Risk Prostate Cancer

To determine if patients (pts) with unfavorable-intermediate risk (UIR), high risk (HR), or very high risk (VHR) prostate cancer (PCa) treated with 125I brachytherapy benefit from androgen deprivation therapy (ADT). We reviewed an institutional database of pts with UIR, HR, or VHR PCa (per NCCN v4.2019) treated with definitive 125I interstitial brachytherapy with or without ADT from 1998-2017. Men treated with external beam radiation were excluded. Outcomes, including biochemical failure (bF), distant metastases (DM), and overall survival (OS) were analyzed with the Kaplan Meier method and Cox proportional hazards regression. PCa specific mortality (PCSM) was analyzed with Fine-Gray competing risk regression. P values <.05 were considered statistically significant. Of 1033 pts, 262 (25%) received ADT and 771 (75%) did not. Median duration of ADT was 6 months (standard deviation [SD], 3.5 months). By risk group, 764 (74%) pts had UIR PCa, 219 (21%) HR, and 50 (5%) VHR. ADT was more likely to be given to pts with HR (50%) and VHR (56%) PCa, compared to UIR (16%; p<.001). There was corresponding greater use of ADT with increasing PSA (p<.001) and Grade Group (p<.001). Pts who were older were more likely to receive ADT (median 70 years [yrs]; SD, 7.7 v median 68 yrs; SD, 7.3; p<.001). Median follow up was 4.9 yrs (range, 0.3-17.6 yrs). On univariable analysis, ADT usage was associated with worse OS (10 yr OS, 63.6% [95% CI, 54.2-73.0%) with ADT v 74.7% [68.0-81.4%] without ADT; p = .036), but there were no differences in bF, DM, or PCSM (p≥.05 each). On multivariable analysis (MVA; Table) adjusting for risk group, age, and year of treatment, ADT was not associated with bF, DM, PCSM, or OS (p≥.05 each). When stratified by risk group, ADT usage was not associated with improved bF, DM, PCSM, or OS for UIR, HR, or VHR PCa (p≥.05 each). Among pts with UIR, HR, or VHR PCa, the addition of short-term ADT to 125I brachytherapy was not associated with improved outcomes in any subgroup. Our findings do not support the use of short-term ADT in combination with 125I interstitial brachytherapy. Additional analysis is required to determine if ADT was associated with worse survival when accounting for comorbidities and cause of death, such as cardiac death.Abstract 4122; TableMVAbFDMPCSMOSHR (95% CI)pHR (95% CI)pHR (95% CI)pHR (95% CI)pADT no v yes1.03 (.74-1.44).851.39 (.86-2.25).18.92 (.31-2.67).881.03 (.70-1.51).88Risk GroupHR v UIR2.20 (1.59-3.03)<.0011.96 (1.23-3.13).0051.79 (.58-5.50).311.33 (.88-2.020.17VHR v UIR2.82 (1.57-5.07)<.0015.01 (2.48-10.11)<.0018.00 (2.23-28.67).0013.93 (2.22-6.96)<.001VHR v HR1.29 (.72-2.29).402.56 (1.27-5.15).0094.47 (1.38-14.55).0132.95 (1.64-5.29)<.001Age.99 (.97-1.01).271.01 (0.98-1.04).411.06 (1.00-1.13).071.08 (1.06-1.11)<.001Yr of Treatment1.02 (098-1.06).371.08 (1.01-1.14).018.93 (.83-1.04).20.97 (.92-1.02)0.22 Open table in a new tab

PD63-01 RADICAL PROSTATECTOMY FOR PATIENTS WITH HIGH-RISK, VERY-HIGH RISK, OR METASTATIC PROSTATE CANCER: ONCOLOGIC RESULTS FROM THE MUSIC STATEWIDE COLLABORATIVE

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy V (PD63)1 Apr 2020PD63-01 RADICAL PROSTATECTOMY FOR PATIENTS WITH HIGH-RISK, VERY-HIGH RISK, OR METASTATIC PROSTATE CANCER: ONCOLOGIC RESULTS FROM THE MUSIC STATEWIDE COLLABORATIVE Brian Lane*, Silvia Mora, Ji Qi, Todd Morgan, Christopher Brede, James Peabody, Arvin George, and for the Michigan Urological Surgery Improvement Collaborative Brian Lane*Brian Lane* More articles by this author , Silvia MoraSilvia Mora More articles by this author , Ji QiJi Qi More articles by this author , Todd MorganTodd Morgan More articles by this author , Christopher BredeChristopher Brede More articles by this author , James PeabodyJames Peabody More articles by this author , Arvin GeorgeArvin George More articles by this author , and for the Michigan Urological Surgery Improvement Collaborative for the Michigan Urological Surgery Improvement Collaborative More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000980.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Guideline-recommended management of high risk (HR) prostate cancer (PCa) is radical prostatectomy with pelvic lymph node dissection (RP+PLND) or radiation therapy with/without systemic therapy. Increasingly, patients with regional (N1) and distant (M1) metastases are being considered for definitive local therapy. We investigated the oncologic outcomes of surgery for patients categorized as HR, very-high risk (VHR), or with suspected metastatic (N1 and/or M1) PCa at the time of RP. METHODS: The MUSIC registry was queried for all RP from 1/2012 to 12/ 2018. Of the 9208 patients, 2023 patients (22%) were classified as having HR PCa or higher. HR PCa was defined as having PSA≥20 or cT3-4 or biopsy grade group (bGG) 4-5;VHR PCa was defined as having ≥2 HR features, or >4 cores of bGG 4-5, or primary pattern 5. Metastatic PCa was defined as clinical N1 and/or M1 disease. The pre-treatment and oncologic outcomes of the HR, VHR, and metastatic groups were compared. Kaplan-Meier analysis of biochemical recurrence (BCR) and multivariable analyses were performed with significance set at p<0.05. RESULTS: At median follow-up of 20.8 months after RP, overall 3-year BCR-free probability was 66% for HR, 49% for VHR, and 47% for metastatic PCa patients (p<0.001). In multivariable analysis, the highly significant (p<0.001) predictors of BCR included PSA (Hazard Ratio: 3.35 (95%CI:2.32,4.83) for PSA>50, 2.35 (1.87,2.96) for PSA 20-50, and 2.07 (1.71,2.51) for PSA 10-20 vs. PSA<10) and risk group (1.63 (1.22,2.18) for metastatic and 1.45 (1.18,1.77) for VHR vs. HR). bGG 3-5, cT2-T4, and African-American race were significant BCR predictors. CONCLUSIONS: Nearly 25% of RP were performed for HR or higher PCa. Although these patients are clearly at higher risk for BCR and many received additional treatments for PCa, the majority are disease-free 3 years after surgery. RP appears to be an oncologically-sound approach for patients with HR and VHR PCa. Patients with suspicion of N1 or M1 disease that undergo RP appear to have similar oncologic outcomes to non-metastatic VHR patients. The value of local treatment in the setting of confirmed metastatic disease is the focus of ongoing clinical trials, and is best performed in this setting. Source of Funding: Betz Family Endowment for Cancer ResearchBlue Cross Blue Shield of Michigan © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1292-e1292 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Brian Lane* More articles by this author Silvia Mora More articles by this author Ji Qi More articles by this author Todd Morgan More articles by this author Christopher Brede More articles by this author James Peabody More articles by this author Arvin George More articles by this author for the Michigan Urological Surgery Improvement Collaborative More articles by this author Expand All Advertisement PDF downloadLoading ...

Biochemical relapse in very high-risk prostate cancer after radical prostatectomy and DC-vaccine loaded with tumor RNA, hTERT, and survivin.

324 Background: Patients with very high-risk prostate cancer (VHR-PC) features experience worse outcome after radical prostatectomy. This study was designed to assess biochemical failure and toxicity of adjuvant dendritic cells vaccine (DCV) in prostate cancer patients who are at greatest risk for cancer progression. Methods: Twenty patients with pathological stage pT2 - pT3b and Gleason score 7B-10, pN0, pN+ or pNx were enrolled into the approved study DC-005. The primary end point was clinical failure. Ten patients were tested for disseminated tumor cells (DTCs) to the bone marrow before inclusion to the study. Three patients out of 10 patients had positive DTCs detection in bone marrow. The mean age of the cohort was 63 years (SD 6.9 years), and three patients had postsurgical pN1 status. Eighteen patients had two or more high-risk factors (ISUP grade 5, T3- stage and or PSA &gt; 20 ng/mL). Autologous dendritic cells were transfected with mRNA for hTERT, survivin and tumor mRNA. The DCV product was applied intradermally after curative intended surgery once per week the first months, then once per months the first year, thereafter every 3 months for two years or until biochemical progression (PSA relapse cut-off ≥ 0.3). Results: After 5 years follow-up (FU) 62% (12/20 patients) had not biochemically progressed and with a median FU of 69 months all patients included in the study are alive. Five patients were treated with salvage and one patient with adjuvant radiation treatment, three patients received limited ADT, and three patients are on first line ADT, none of those eight patients have experienced castration resistant prostate cancer. The toxicity was mild with no serious adverse event related to DCV. Conclusions: Adjuvant DCV mitigates the time to biochemical progression. These results appear favorably compared to historical controls in VHR-PC. The clinical outcomes of this study warrants a future enlarged clinical trial. Clinical trial information: NCT01197625.

Impact and Outcomes of Pretreatment Total Serum Testosterone on Localized Prostate Cancer Patients.

Purpose To investigate how pretreatment testosterone levels correlate with progression-free survival, metastasis-free survival, and overall survival in a propensity-adjusted localized prostate cancer population. Methods Men diagnosed with clinical NCCN-risk stratified very-low, low, intermediate, high, and/or very-high risk prostate cancer who had a baseline total serum testosterone level≥100 ng/dl measured within the 100 days preceding the first definitive therapy were identified from our prospectively gathered institutional database. Cohorts below (100–239 ng/dl), within (240–593 ng/dl), or above (594 + ng/dl) one standard deviation from the mean testosterone level (416 ng/dl) were used for comparison. Progression-free, metastasis-free, and overall survival were evaluated. A separate cohort of men not receiving ADT was used to evaluate testosterone recovery after various treatment modalities (surgery, external beam radiation, brachytherapy, or combined EBRT + Brachy). Results There was no statistically significant difference between the low, average, and high testosterone cohorts for PFS, MFS, or OS. In men not using ADT, there were no statistically significant changes in testosterone levels 1 year after therapy, regardless of therapy type. Conclusion In men with serum testosterone levels >=100 ng/dl at diagnosis, baseline testosterone does not impact PFS, MFS, or OS. Recovery of testosterone back to baseline is expected for men undergoing either surgery, external beam or brachytherapy, or combined modality radiation when not using ADT.

Superior survival benefits of Radical Prostatectomy than External Beam Radiotherapy in aging 75 and older men with high-risk or very high-risk Prostate Cancer: a population-matched study.

Objective: To evaluate the survival difference of radical prostatectomy (RP) and external beam radiotherapy (EBRT) in elderly men (75 years and older) with high-risk (HR) or very high-risk (VHR) prostate cancer (PCa).Methods: Elderly men diagnosed with HR/VHR PCa from 2004-2015 in the Surveillance, Epidemiology and End Results (SEER) database were identified. Propensity-score matching (PSM) was conducted to balance the covariates; Kaplan-Meier and Cox analysis were performed to evaluate the overall survival (OS) and prostate cancer-specific survival (PCSS).Results: 11698 patients with HR PCa and 4415 patients with VHR PCa were identified and divided into RP and EBRT group. After PSM, 964 patients with HR PCa and 538 patients with VHR PCa were included in each group. The 10-year OS and PCSS of men with HR PCa were 60.1% vs 40.9% and 90.6% vs 83.4%, respectively. The 10-year rate of OS and PCSS in men with VHR PCa were 55.9% vs 33.3% and 82.4% vs 75.6%, respectively. The OS curve of patients with HR PCa revealed that RP was significantly better than EBRT in both overall cohort [HR: 0.533, 95%CI (0.485~0.586), p<0.001] and the matched cohort [HR: 0.703, 95%CI (0.595~0.832), p<0.001]. However, the PCSS curve of patients with HR PCa showed that RP was significantly better than EBRT in overall cohort [HR: 0.453, 95%CI (0.368~0.559), p<0.001] but was similar to EBRT in matched cohort [HR: 0.820, 95%CI (0.552~1.218), p=0.327]. As for patients with VHR PCa, RP was associated with better OS than EBRT whether in overall cohort [HR: 0.520, 95%CI (0.457~0.592), p<0.001] or matched cohort [0.695, 95%CI (0.551~0.876), p=0.002]. The PCSS of RP was significantly better than that of EBRT in overall cohort [HR: 0.538, 95%CI (0.422~ 0.685), p<0.001], but was similar in matched cohort [HR: 0.787, 95%CI (0.510 ~1.214), p=0.281].Conclusions: RP has more survival benefits than EBRT in men aged 75 years and older with HR or VHR PCa.

Ten-year outcomes of high-dose intensity-modulated radiation therapy for nonmetastatic prostate cancer with unfavorable risk: early initiation of salvage therapy may replace long-term adjuvant androgen deprivation

BackgroundThe optimal timing of salvage androgen deprivation therapy (ADT) following definitive radiation therapy for prostate cancer (PCa) is unknown. This study evaluated the efficacy of early initiation of salvage-ADT (S-ADT) based on predetermined timing among patients with unfavorable PCa treated with high-dose intensity-modulated radiation therapy (IMRT).Materials and methodsHigh-risk (HR) and very-high-risk (VHR) PCa patients treated with IMRT at our institution between September 2000 and December 2010 were analyzed retrospectively. Treatment consisted of high-dose IMRT (78 Gy/39 fractions) combined with 6 months of neoadjuvant-ADT (NA-ADT). S-ADT was initiated when prostate-specific antigen levels exceeded 4.0 ng/mL.ResultsIn total, 268 (184 HR and 84 VHR) patients were analyzed. The median follow-up period was 114.4 months. The 10-year overall survival (OS), PCa-specific survival (PCSS), biochemical failure (BF), and clinical failure (CF) rates were 82.8%, 97.1%, 27.3%, and 12.8% among the HR PCa patients and 79.4%, 87.9%, 56.2%, and 26.7% among the VHR PCa patients (p = 0.839, = 0.0377, < 0.001, and < 0.001), respectively. The 10-year cumulative incidence rates of urinary and rectal (grades 2–3) toxicities were 22.6% and 5.8%, respectively. No grade 4 or higher toxicities were observed.ConclusionHigh-dose IMRT combined with short-term NA-ADT resulted in long-term disease-free status, with acceptable morbidity among approximately three-fourths of the HR PCa patients and nearly half of the VHR PCa patients. Moreover, excellent survival outcomes were achieved by the early S-ADT initiation. This approach may be a promising alternative to uniform provision of long-term ADT.