Low free and bioavailable testosterone levels may predict pathologicallyproven high-risk prostate cancer: a prospective, clinical trial

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.

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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.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.tps138 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. TPS138-TPS138 ◽

Cited By ~ 1

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.

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

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.324 ◽

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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