A randomized, multicenter, prospective PHASE II trial to assess the effect of short- versus long-term adjuvant ADT with high dose salvage radiotherapy on distant metastasis free survival in case of biochemical relapse (BR) after radical prostatectomy.
Radical prostatectomy (RP) is one of the standard treatment options for localized and locally advanced prostate cancer. RP should be combined with an extended pelvic lymph node dissection (ePLND) when the risk of pelvic involvement becomes substantial, at least 7%. In case of node-negative disease (pN0), adverse pathological features at examination of the RP-specimen such as extra-capsular extension (ECE), seminal vesicle invasion (SVI) and positive surgical margins (PSM) increase the risk of biochemical relapse (BR) and/or isolated local relapse (LR). Both a BR and LR, if not adequately treated, can finally result in the development of distant metastasis. In case of BR and/or LR, salvage radiotherapy (SRT) is the only treatment option with curative intent. Several factors play a significant role in predicting the outcome after SRT: Gleason score, pre-SRT PSA, pre-SRT doubling time, SVI, SRT dose and duration of adjuvant androgen deprivation therapy (ADT) associated with SRT. The 2 latter variables have never been tested in a randomized controlled trial. The GETUG-AFU 16 trial randomized between no vs. 6 months ADT while patients received 66 Gy to the prostate bed and 46 Gy to the pelvis. Moreover, the pN0 status was not needed for inclusion. Also the RADICALS trial is currently running this comparison with a radiation dose of 66 Gy to the prostate bed and also no information on pN status is needed to be included in this study. In the LOBSTER study, the pN0 status is obligatory and the prescription dose is set at 70 Gy to the prostate bed and seminal vesicles. These conditions make this study unique compared to other already conducted and currently running trials. In previous work, it has been demonstrated that ADT, added for 6 months to SRT, significantly improved biochemical relapse free survival at 5 years. Added to this, there is recent evidence that using a longer schedule of adjuvant ADT might be beneficial when compared to a 6-months schedule. Unfortunately, none of these suggestions are based on evidence coming from a randomized controlled trial. Therefore, this randomized phase 2 trial 'LOBSTER' is conducted, comparing 6 versus 24 months of adjuvant ADT together with high-dose SRT in case of BR after RP in pN0 prostate cancer patients
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
394
Comparison of the duration of ADT (Triptoreline)
AZ Maria Middelares
Ghent, Belgium
RECRUITINGUZ Gent
Ghent, Belgium
RECRUITINGUZ Leuven
Leuven, Belgium
RECRUITINGMetastasis-free survival
Time to appearance of M1a-b-c disease. In order to assess the absence/presence of M1a-M1c disease as early as possible, top-of-the-line imaging will be conducted in case of BR during follow-up after SRT and after agreement of the multidisciplinary uro-oncology team. Time point zero is the last day of radiotherapy (also applies for secondary endpoints). Top of the line imaging includes: CT thorax abdomen and bone scintigraphy (standard). PSMA PET-CT is allowed but not obligatory. Patients who are also included in the diagnostic imaging study are required to receive a PSMA PET-CT. Whole body MRI is allowed but not obligatory. BR is defined as any rise in PSA above the level of 0.2 ng/ml after a postradiotherapy nadir or a continued rise in the serum PSA despite salvage treatment (3). In case a BR is not accompanied by metastatic progression, PSMA PET/CT will be repeated every 6 months or earlier in case of prostate cancer-related symptoms.
Time frame: 5 years
Pelvic recurrence-free survival
time to appearance of local recurrence (prostate bed) and/or N1 disease (positive lymph node(s) below the aortic bifurcation) using PSMA PET/CT and triggered by biochemical relapse.
Time frame: up to 10 years after randomization
Clinical progression-free survival
time to appearance of any recurrence (local recurrence, N1 (positive lymph node(s) below the aortic bifurcation), M1a-c disease) and triggered by biochemical relapse.
Time frame: up to 10 years after randomization
(Palliative) Systemic therapy-free survival
time to the start of palliative ADT
Time frame: up to 20 years (or more) after randomization
Time to CRPC
time to biochemical and/or clinical progression at castrate testosterone levels (\<50 ng/dl). Progression is defined as three consecutive PSA rises (1 week interval), of which at least 2 rises with a PSA level of \> 2 ng/ml and a rise of 50% of the nadir PSA level, progression of bone lesions (2 or more new bone lesions detected on bone scan), progression of soft tissue lesions according to RECIST criteria or the appearance of one or more new visceral or soft tissue (inclusive lymph node) metastasis.
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Time frame: up to 20 years (or more) after randomization
Cause-specific survival (CSS)
freedom from dying from prostate cancer (K-M statistics)
Time frame: up to 20 years (or more) after randomization
Overall survival (OS)
freedom from dying from any cause (K-M statistics)
Time frame: up to 20 years (or more) after randomization
Acute toxicity
adverse effects according to the CTCAE version 4.0
Time frame: during RT, up to three months after radiation therapy
Late toxicity
adverse effects according to the CTCAE version 4.0
Time frame: starting from more than three months after radiation therapy, up to 5 years after radiotherapy
Quality of life assessment
EORTC QLQ-C30
Time frame: up to 5 years after randomization
Quality of life assessment
EORTC QLQ-PR25
Time frame: up to 5 years after randomization
Quality of life assessment
EQ-5D-5L
Time frame: up to 5 years after randomization