Early Salvage Therapy for Patients With Advanced Features for Biochemical Relapse After Radical Prostatectomy for Localized Prostate Carcinoma In Correlation With Supposed Molecular-genetic Parameters of Higher Aggressiveness (ESTABLISH)

General University Hospital, Prague

Status and phase: Not yet enrolling; Phase 3

Conditions: Prostate Cancer

Treatments: Radiation: Delayed Salvage radiotherapy (dSRT); Radiation: Early salvage radiotherapy (eSRT)

Study type: Interventional

Funder types: Other

Identifiers

NCT05232578

ESTABLISH 2021 Trial v03.2021

Details and patient eligibility

About

The primary objective of the trial is to compare the impact and safety of delayed salvage therapy (dSRT, i.e., SRT initiated at PSA values of 0.4-0.5 ng/ml) to those of early salvage therapy (eSRT, i.e., at PSA levels of 0.2 ng/ml) in patients with biochemical relapse after radical prostatectomy.

The secondary objective of the trial is to perform analysis of the subgroups of patients to determine which patients are most likely to benefit from dSRT

Exploratory objective of the trial is to determine whether selected molecular genetic parameters (172 candidate genes and molecular alterations) and known clinical parameters can be used to identify potential predictors of worse prognosis in patients with known risk factors for relapse after radical prostatectomy, thereby augmenting and refining patient stratification, optimizing their therapy, and clarifying the proper timing of multimodal therapy

Enrollment: 380 estimated patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• > 18 years of age

• Pathologically confirmed invasive prostate carcinoma with minimal 1 risk factor (RF) after radical prostatectomy (RP)

• Patient refuses the adjuvant therapy after normalization of urinary function within 6 month after RP

• Signed informed consent to participate in the study and (where necessary) consent to participate in the translational part of the research (not a requirement)

• ECOG 0 - 1

• pT2 and minimal 1 risk factor (RF):

  • R1 (PSM), and/or
  • Gleason score (4+3=7) 8-10 and/or ISUP grade group 3-5

• pT3a /pT3b with or without one RF

• No evidence of suspicious pelvic lymph nodes by initial diagnostic: cN0 and/or pN0

• No evidence of suspicious distant metastases by initial diagnostic: M0

• Patient with decline of PSA level to undetectable PSA levels (< 0,1 ng/ml) or around 0,2ng/ml and with another decreasing trends so that the PSA level decline within 12-24 weeks after RP to undetectable levels (< 0,1 ng/ml) and with renewed increase of PSA >0,2 ng/ml (BCR= biochemical relapse) without any clinical relapse on PSMA PET/CT

• No hormonal therapy prior and /or after the radical prostatectomy

• Patient suitable and fit for subsequent radiotherapy with high likelihood of good compliance to the follow-up

Exclusion criteria

• Life expectancy (based on Charlson comorbidity index) < 10 years
• Patient not fit for the therapy
• History of other cancer (other than a radically removed non-melanoma skin carcinoma)
• Previous pelvic irradiation
• Active immunosuppressive medication
• History of hormone therapy prior to randomization
• cN1 and/or pN1 and M1
• PSA-persistence after RP (PSA 12-weeks after RP > 0.1 ng/ml or no decreasing trend described in Inclusion criteria)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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380 participants in 2 patient groups

Arm A- early salvage radiotherapy (eSRT)

Experimental group

Description:

Early salvage radiotherapy (eSRT) will be administered immediately after the confirmation of the biochemical relapse (prostate-specific antigen PSA level increase to ≈ 0,2 ng/ml) after radical prostatectomy with defined risk factors and no clinical recurrence signs on prostate specific membrane antigen positron emission tomography and computed tomography (PSMA PET/CT).

Treatment:

Radiation: Early salvage radiotherapy (eSRT)

Arm B- delayed salvage radiotherapy (dSRT)

Experimental group

Description:

The patient is by the biochemical relapse analysis (PSA level 0,2 ng/ml) referred for further follow-up of PSA values. dSRT is initiated, if PSA further increase to values of ≥ 0.4 ng/ml is confirmed and the presence of a potential clinical relapse is excluded with repeated PSMA-PET-CT in line with standard procedures

Treatment:

Radiation: Delayed Salvage radiotherapy (dSRT)