scholarly journals Clinical-Genomic Sub-classification of High-Risk Prostate Cancer: Implications for Tailoring Therapy and Clinical Trial Design

2020 ◽  
Vol 108 (3) ◽  
pp. e854
Author(s):  
V. Muralidhar ◽  
M. Alshalalfa ◽  
D.E. Spratt ◽  
S. Liu ◽  
R.J. Karnes ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
High Risk ◽  
Trial Design ◽  
Clinical Trial Design ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer ◽  
Clinical Genomic

Genomic validation of three-tiered sub-classification of high-risk prostate cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 17-17
Author(s):  
Vinayak Muralidhar ◽  
Jingbin Zhang ◽  
Daniel Eidelberg Spratt ◽  
Felix Y Feng ◽  
Elai Davicioni ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Intermediate Risk ◽  
High Risk Prostate Cancer ◽  
High Risk Disease ◽  
Genomic Markers ◽  
Risk Prostate Cancer ◽  
Clinical Genomic ◽  
Very High

17 Background: Recent data and National Comprehensive Cancer Network (NCCN) guidelines suggest that high-risk prostate cancer (cT3-4, Gleason score ≥ 8, or prostate-specific antigen [PSA] > 20 ng/mL) is a heterogenous group in terms of long-term patient outcomes. We sought to determine whether sub-classification of high-risk prostate cancer based on clinical factors correlates with genomic markers of risk. Methods: We identified 3,220 patients with NCCN unfavorable intermediate-risk (n=2,000) or high-risk (n=1,220) prostate cancer. We defined the following sub-classification of high-risk prostate cancer based on previously published data: favorable high-risk (cT1c, Gleason 6, and PSA > 20 ng/mL or cT1c, Gleason 4+4=8, PSA < 10 ng/mL); very high-risk (cT3b-T4 or primary Gleason pattern 5); and standard high-risk (all others with cT3a, Gleason score ≥ 8, or PSA > 20 ng/mL). We used a set of 37 previously published genomic classifiers, including the 22-gene Decipher assay, to determine whether high-risk genomic features correlated with the clinical sub-classification of high-risk prostate cancer. Results: Among those with favorable high-risk, standard high-risk, and very high-risk prostate cancer, 50.4%, 64.2%, 81.6% had a high-risk Decipher score, respectively (p < 0.001). Among 36 other genomic signatures, 33 had a similar increasing trend across the three sub-classes of high-risk (p < 0.05 after correction for multiple hypothesis testing). Patients in the three sub-classes of high-risk disease were positive for a median number of 5, 7, and 14 high-risk signatures. Under a novel clinical-genomic risk group classification (Spratt et al., 2017), 27.5%, 19.7%, and 7.0% of patients with favorable, standard, or very high-risk disease would be re-classified as intermediate-risk, respectively. In comparison, among those with unfavorable intermediate-risk prostate cancer, 38.2% had a high-risk Decipher score and would be re-classified as clinical-genomic high-risk. Conclusions: Genomic markers of risk correlate with the clinical sub-classification of high-risk prostate cancer into favorable high-risk, standard high-risk, and very high-risk disease, validating the prognostic utility of this stratification.

scholarly journals Unpacking Trial Offers and Low Accrual Rates: A Qualitative Analysis of Clinic Visits With Physicians and Patients Potentially Eligible for a Prostate Cancer Clinical Trial

2020 ◽  
Vol 16 (2) ◽  
pp. e124-e131
Author(s):  
Lauren M. Hamel ◽  
David W. Dougherty ◽  
Terrance L. Albrecht ◽  
Mark Wojda ◽  
Alice Jordan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Cancer Clinical Trial ◽  
Cancer Center ◽  
Contributing Factors ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer ◽  
Clinical Trial Accrual ◽  
Clinical Interactions

PURPOSE: Cancer clinical trial accrual rates are low, and information about contributing factors is needed. We examined video-recorded clinical interactions to identify circumstances under which patients potentially eligible for a trial at a major cancer center were offered a trial. METHODS: We conducted a qualitative directed content analysis of 62 recorded interactions with physicians (n = 13) and patients with intermediate- or high-risk prostate cancer (n = 43). Patients were screened and potentially eligible for a trial. We observed and coded the interactions in 3 steps: (1) classification of all interactions as explicit offer, offer pending, trial discussed/not offered, or trial not discussed; (2) in interactions with no explicit offer, classification of whether the cancer had progressed; (3) in interactions classified as progression but no trial offered, identification of factors discussed that may explain the lack of an offer. RESULTS: Of the 62 interactions, 29% were classified as explicit offer, 12% as offer pending, 18% as trial discussed/not offered, and 39% as trial not discussed. Of those with no offer, 57% included information that the cancer had not progressed. In 68% of the remaining interactions with patients whose cancer had progressed but did not receive an offer, reasons for the lack of offer were identified, but in 32%, no explanation was provided. CONCLUSION: Even in optimal circumstances, few patients were offered a trial, often because their cancer had not progressed. Findings support professional recommendations to broaden trial inclusion criteria. Findings suggest accrual rates should reflect the proportion of eligible patients who enroll.

Phase II Multi-institutional Clinical Trial on a New Mixed Beam RT Scheme of IMRT on Pelvis Combined with a Carbon Ion Boost for High-risk Prostate Cancer Patients

2016 ◽  
Vol 103 (3) ◽  
pp. 314-318 ◽  
Author(s):  
Giulia Marvaso ◽  
Barbara A. Jereczek-Fossa ◽  
Barbara Vischioni ◽  
Delia Ciardo ◽  
Tommaso Giandini ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
High Risk ◽  
Phase Ii ◽  
Carbon Ions ◽  
Carbon Ion ◽  
High Risk Prostate Cancer ◽  
Mixed Beam ◽  
Risk Prostate Cancer

Purpose Definition of the optimal treatment schedule for high-risk prostate cancer is under debate. A combination of photon intensity modulated radiotherapy (IMRT) on pelvis with a carbon ion boost might be the optimal treatment scheme to escalate the dose on prostate and deliver curative dose with respect to normal tissue and quality of dose distributions. In fact, carbon ion beams offer the advantage to deliver hypofractionated radiotherapy (RT) using a significantly smaller number of fractions compared to conventional RT without increasing risks of late effects. Methods This study is a prospective phase II clinical trial exploring safety and feasibility of a mixed beam scheme of carbon ion prostate boost followed by photon IMRT on pelvis. The study is designed to enroll 65 patients with localized high-risk prostate cancer at 3 different oncologic hospitals: Istituto Europeo di Oncologia, Fondazione IRCCS Istituto Nazionale dei Tumori, and Centro Nazionale di Adroterapia Oncologica. The primary endpoint is the evaluation of safety and feasibility with acute toxicity scored up to 1 month after the end of RT. Secondary endpoints are treatment early (3 months after the end of RT) and long-term tolerability, quality of life, and efficacy. Results The study is not yet recruiting; in silico studies are ongoing and we expect to start recruitment by 2017. Conclusions The present clinical trial aims at improving the current treatment for high-risk prostate cancer, evaluating safety and feasibility of a new RT mixed-beam scheme including photons and carbon ions. Encouraging results are coming from carbon ion facilities worldwide on the treatment of different tumors including prostate cancers. Carbon ions combine physical properties allowing for high dose conformity and advantageous radiobiological characteristics. The proposed mixed beam treatment has the advantage to combine a photon high conformity standard of care IMRT phase with a hypofractionated carbon ion RT boost delivered in a short overall treatment time.

The “ProPSMA Study” clinical trial protocol: A prospective randomized multi-center study of the impact of Ga-68 PSMA PET/CT imaging for staging high-risk prostate cancer prior to curative-intent surgery or radiotherapy.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. TPS138-TPS138 ◽  
Author(s):  
Michael Hofman ◽  
Declan G. Murphy ◽  
Scott Williams ◽  
Tatenda Nzenza ◽  
Alan Herschtal ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
High Risk ◽  
Conventional Imaging ◽  
Curative Intent ◽  
High Risk Prostate Cancer ◽  
Psma Pet ◽  
Pet Ct ◽  
Risk Prostate Cancer

TPS138 Background: Disease persistence or relapse following curative-intent surgery or radiotherapy of high-risk prostate cancer is not uncommon. This is attributable, in part, to a failure of accurate staging with diagnostic imaging being insensitive for detection of small volume metastatic disease. Prostate-specific-membrane-antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is a new whole body scanning technique that enables visualisation of prostate cancer with high sensitivity. The hypotheses of this study are that PSMA-PET/CT (a) has improved diagnostic accuracy compared to conventional imaging, (b) should be used as a first-line diagnostic test for staging, (c) the improved diagnostic accuracy will result in significant management impact and (d) provides economic benefits when incorporated into the management algorithm. Methods: This is a 300 patient phase III multi-centre randomized study of patients with untreated high-risk prostate cancer defined by Gleason grade group 3-5, PSA ≥ 20ng/ml or clinical stage ≥ T3. Patients are randomized to Gallium-68-PSMA11 PET/CT or conventional imaging, consisting of computer tomography of the abdomen/pelvis and bone scintigraphy with SPECT/CT. Patients with negative, equivocal or oligometastatic disease cross-over to receive the other imaging arm. The primary objective is to compare the accuracy of PSMA-PET/CT to conventional imaging for detecting nodal or distant metastatic disease. Accuracy is defined by a pre-defined “ground truth” scoring system incorporating histopathologic, imaging and clinical follow-up at six months post randomisation. Secondary objectives include comparing management impact, the number of equivocal studies, the incremental value of second-line imaging in patients who cross-over, health economics, radiation exposure, inter-observer agreement and safety of PSMA-PET/CT. Longer term follow-up will also assess the prognostic value of a negative PSMA-PET/CT. 294 of 300 (98%) patients randomised at time of abstract submission. Clinical trial information: 12617000005358.

Clinical-genomic sub-classification of high-risk prostate cancer: Implications for tailoring therapy and clinical trial design.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 337-337
Author(s):  
Vinayak Muralidhar ◽  
Mohammed Alshalalfa ◽  
Daniel Eidelberg Spratt ◽  
Yang Liu ◽  
R. Jeffrey Karnes ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Risk Stratification ◽  
High Risk Prostate Cancer ◽  
High Risk Disease ◽  
Risk Prostate Cancer ◽  
Risk Patients ◽  
Genomic Risk ◽  
Clinical Genomic ◽  
Very High

337 Background: Current risk stratification schema have limited prognostic performance in predicting outcome within National Comprehensive Cancer Network (NCCN) high-risk to very high-risk prostate cancer. Methods: Two multicenter high-risk cohorts were used for training (n = 214) and validation (n = 151) of a novel RNA microarray-based integrated clinical-genomic Classifier Optimized for Outcome in High-risk Prostate cancer (COOHP) to classify patients as COOHP favorable high-risk, standard high-risk, or very high-risk. Cox analysis was used to model metastasis-free survival (MFS), prostate cancer-specific survival (PCSS), and overall survival (OS). Model performance was compared to prior sub-classification systems using time-dependent c-indices. Results: Among NCCN high/very high-risk patients in the training cohort, 11% were classified as COOHP favorable high-risk, 70% as COOHP standard high-risk, and 18% as COOHP very high-risk. Patients with COOHP favorable high-risk disease had better rates of 5-year MFS compared to those with COOHP standard high-risk disease (94% vs 76%, hazard ratio [HR] 0.10, p = 0.02), and patients with COOHP very high-risk disease had worse 5-year MFS compared to those with COOHP standard high-risk disease (34% vs 76%, HR 3.5, p < 0.0001). Similarly, patients with COOHP very high-risk disease had worse 10-year PCSS compared to those with COOHP standard high-risk disease (36% vs 82%, HR 4.4, p < 0.0001). The c-indices for 5-year MFS and 10-year PCSS in the training cohort were 0.80 and 0.74, significantly improved compared to prior clinical and clinical-genomic risk stratification systems (0.62-0.69 for 5-year MFS and 0.56-0.63 for 10-year PCSS). These results were consistent in the validation cohort, where 5-year MFS significantly varied among the three COOHP subgroups (100% vs 89% vs 79%, p = 0.020), as did 10-year OS (100% vs 71% vs 53%, p = .040). Conclusions: A clinical-genomic risk stratification system specifically designed to discriminate prognosis in high-risk prostate cancer better identified favorable high-risk and very high-risk subsets of disease compared to prior clinical and clinical-genomic stratification systems.

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

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 324-324
Author(s):  
Wolfgang Lilleby ◽  
Anne Merete Tryggestad ◽  
Iris Bigalke ◽  
Bjørn Brennhovd ◽  
Karol Axcrona ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Bone Marrow ◽  
Dendritic Cells ◽  
High Risk ◽  
Radical Prostatectomy ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer ◽  
Biochemical Progression ◽  
Very High

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 > 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.

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