Cancer Recurrence, Prostate Cancer
Conditions
Keywords
PSMA-PET/CT, Salvage, Hypofractionation, Radiotherapy, Prostatectomy
Brief summary
After radical prostatectomy approximately 15-40% of men develop a biochemical recurrence (BR) within 5 years. The standard treatment of post-prostatectomy BR is salvage external beam radiation therapy (sEBRT). sEBRT can provide long-term disease control; with 5 year biochemical progression-free survival (bPFS) up to 60% and with most treatment failures in the first 2 years after sEBRT. The main goal of this project is to investigate whether the oncologic outcome in patients with post-prostatectomy recurrent PCa can be improved, by increasing the biological effective radiation dose using a hypofractionated schedule of 20 x 3 = 60 Gy. The study is designed as a prospective open phase III randomized multicenter trial. All patients with biochemical recurrence with a PSA \< 1.0 ng/ml after radical prostatectomy for prostate cancer without evidence of lymph nodes or distance metastases will be included. PSA progression after prostatectomy defined as two consecutive rises with the final PSA \> 0.1 ng/mL or three consecutive rises will be included. All eligible patients will be randomized to one of the following two treatment arms: Arm 1 = Conventional sEBRT to apply a total dose of 70 Gy in 35 daily fractions of 2 Gy during 7 weeks. Arm 2 = Hypofractionated sEBRT to apply a total dose of 60 Gy in 20 fractions of 3 Gy during 4 weeks. The primary endpoint will be the 5-year progression-free survival (PFS) after treatment.
Interventions
RADIATIONConventional sEBRT
A total dose of70 Gy in 35 daily fractions of 2 Gy during 7 weeks
RADIATIONHypofractionated sEBRT
A total dose of 60 Gy in 20 daily fractions of 3 Gy during 4 weeks
Sponsors
Dutch Cancer Society
University Medical Center Groningen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
no masking
Intervention model description
2 randomised arms
Eligibility
Sex/Gender
MALE
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients with prostate adenocarcinoma treated with radical prostatectomy; * Tumour stage pT2-4, R0-1, pN0, or cN0, cNx according to the UICC TNM 2009, only with Gleason score available; * No lymph node or distant metastases. A recent PSMA-PET scan (\< 60 days) without evidence of lymph node or distant metastases; * PSA progression after prostatectomy defined as two consecutive rises with the final PSA \> 0.1 ng/mL or 3 consecutive rises. The first value must be measured at least 6 weeks after radical prostatectomy; * PSA at inclusion \< 1.0 ng/mL; * WHO performance status 0-2 at inclusion; * Age at inclusion between 18 and 80 years; * Written (signed and dated) informed consent prior to registration.
Exclusion criteria
* Prior pelvic irradiation, (chemo)hormonal therapy or orchiectomy; * Previous or concurrent active invasive cancers other than superficial non-melanoma skin cancers; * Patients with positive nodes or with distant metastases based on the surgical specimen of lymphadenectomy or the following minimum diagnostic workup: PSMA-PET/CT scan, 60 days prior to registration; * Double-sided metallic hip prosthesis; * Inability or unwillingness to understand the information on trial-related topics, to give informed consent or to fill out QoL questionnaires.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 5-year progression-free survival | 5 years | Defined as biochemical progression, clinical progression, loco-regional or distant progression or start with hormonal therapy, whichever occurs first |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acute grade ≥ 2 genitourinary toxicities | Up to 3 months after completion of the RT | As assessed using physician-reported score using questionnaires (CTCAE 5.0 toxicity score). |
| Late grade ≥ 2 gastrointestinal toxicity | Up to 5 years after completion of the RT | As assessed using physician-reported score (CTCAE 5.0 toxicity score). |
| Late grade ≥ 2 genitourinary toxicity | Up to 5 years after completion of the RT | Using physician-reported score (CTCAE 5.0 toxicity score). |
| Acute grade ≥ 2 gastrointestinal toxicity | Up to 3 months after completion of the RT | As assessed using physician-reported score: Common Terminology Criteria for adverse events version 5.0 (CTCAE-5) toxicity score with a scale of 1 - 4. |
| Metastasis-free survival | 5 years | Time from randomisation to the date of metastases reported by CT scan, MRI scan or PSMA-PET/CT during the follow up (date scan). |
| Prostate cancer-specific mortality | 5 years | Prostate cancer-specific mortality. |
| Overall survival | 5 years | Overall survival |
| Quality of life after radiation | Up to 5 years after completion of the RT | As assessed using patient-reported questionnaires: measurend with European platform of cancer research-QLQ C30 |
Countries
Netherlands
Contacts
Primary ContactF. Staal, MD
Backup ContactP. Veldhuijzen van Zanten
Outcome results
None listed