Prostate Cancer
Conditions
Keywords
PSMA-radioguided surgery, ADT, recurrent prostate cancer
Brief summary
ADT with or without robot-assisted PSMA-radioguided surgery for patients with recurrent prostate cancer.
Detailed description
Improving the oncological treatment outcomes in men with a biochemical recurrence after primary prostate cancer (PC) treatment that are diagnosed with a disease recurrence confined to the regional lymph nodes or local residual disease using Prostate Specific Membrane Antigen (PSMA) Positron Emission Tomography and Computed Tomography (PET/CT.) The proposed trial randomizes patients with recurrent PC following primary PC treatment to either 6 months of ADT or Technetium-PSMA-radioguided salvage surgery plus 6 months of ADT. Although the optimal duration of ADT is unknown, a minimal duration of 6 months of ADT seems advisable in this setting and will be mandatory for both arms.
Interventions
PROCEDUREPSMA-radioguided surgery
Approximately 15-24 hours prior to surgery, 400-600 Megabecquerel (MBq) of 99mTc-PSMA-I&S will be intravenously administered to the patient at the Nuclear Medicine department. Following this injection patients will be allowed to return home, and then present for their 99mTechnetium (99mTc)-based PSMA-radioguided salvage surgery the next day.
DRUGADT
Standard 6 months of ADT according to current clinical guidelines. ADT consists of one subcutaneous depot of 22,5mg triptorelin (Pamorelin), with 4 weeks bicalutamide 50mg per os from 2 weeks before till 2 weeks after the first Pamorelin administration.
Sponsors
The Netherlands Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male, aged ≥ 18 years. * Hormone-sensitive recurrent prostate cancer after radical prostatectomy, external beam radiotherapy or brachytherapy * ≤ 2 lymph node metastases or local residual disease within the pelvis with sufficient PSMA expression (≥2 times regional vascular activity level) as determined by PSMA-based PET * PSA-value \< 4 ng/mL in case of a local recurrence and PSA \< 3 ng/ml in case of (a) nodal recurrence(s) * Had a PSMA PET/CT within 90 days before surgery * Suitable for salvage surgery, as per institutional guidelines. * Charlson Comorbidity Index ≤ 4 * World Health Organisation (WHO) performance status 0, 1, or 2. * Written and signed informed consent.
Exclusion criteria
* Other diagnosis of malignancy or evidence of other malignancy within 5 years before screening for this study (except non-melanoma skin cancer). * More than 2 lymph node metastases on PSMA PET/CT * Suspicion of local recurrent prostate cancer within the prostatic fossa not treatable by surgery * Non-regional lymphadenopathy (cM1a) or distant metastases (cM1b/c) as assessed by preoperative PSMA PET/CT. * Castration resistance defined by clinical or biochemical progression despite a combined androgen blockade * Known contraindications to hormone therapy, according to standard recommendations in force * Patient with a psychological, familial, sociological or geographical situation potentially hampering compliance with the study protocol and follow-up schedule * Ongoing androgen deprivation therapy (ADT) or within 6 months prior to surgery. * Severe claustrophobia interfering with PET/CT scanning. * Absence or withdrawal of an informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical progression-free survival (CPFS) | 24 months | CPFS is defined as time between randomization and the appearance of a recurrence (any N1 or M1) as suggested by PSMA PET/CT or symptoms related to progressive PC, or death due to any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Metastasis-free survival (MFS) | 24 months | Metastasis-free survival will be defined as the time between randomization and the appearance of a metastatic recurrence (any M1) as suggested by PSMA PET-CT. |
| Biochemical progression-free survival (BPFS) | 24 months | Biochemical progression-free survival will be defined as the time between randomization and the development of biochemical progression ( three consecutive rises in prostate specific antigen (PSA) 1 week apart, resulting in two 50% increases over the nadir and PSA\>2 ng/ml) |
| Castrate resistant prostate cancer (CRPC) | 10 years | CRPC is defined as castrate serum testosterone\<50 ng/dl plus biochemical progression, i.e., three consecutive rises in PSA 1 week apart, resulting in two 50% increases over the nadir and PSA\>2 ng/ml. |
| Overall survival (OS) | 10 years | Overall survival will be read as the time from trial randomization to the date of death from any cause |
| Incidence of adjuvant therapy | 10 years | ADT, radiation therapy or additional salvage surgery |
| Patient reported QOL as per EORTC-QLQ C30 | 24 months | Quality of life (QoL) will be assessed with the EORTC Core Quality of Life questionnaire's (QLQ-C30) global QoL scale ranging from 0 to 100, higher scores indicate better QoL |
| Negative Predictive Value of 99mTc-PSMA RGS for salvage surgery for recurrent PC compared to histologic evaluation | 30 days | In percentage |
| Complications | 30 and 90 days | Assessment of 99mTc-PSMA-I&S injection-related as well as surgery-related complication rate according to Clavien-Dindo. |
| Number of in-field recurrences | 24 months | Recurrence measured by use of PSMA PET/CT in the template of 99mTc-PSMA-radioguided surgery (RGS) supported salvage surgery |
| Specificity of 99mTc-PSMA RGS for salvage surgery for recurrent PC compared to histologic evaluation | 30 days | In percentage |
| Sensitivity of 99mTc-PSMA RGS for salvage surgery for recurrent PC compared to histologic evaluation | 30 days | In percentage |
| Positive Predictive Value of 99mTc-PSMA RGS for salvage surgery for recurrent PC compared to histologic evaluation | 30 days | In percentage |
| Patient reported QOL as per Expanded Prostate cancer Index Composite (EPIC) 26 | 24 months | Quality of life (QoL) will be assessed with the EPIC 26 questionnaire, containing 26 items covering 5 domains: Urinary Incontinence, Urinary Irritative/Obstructive, Bowel, Sexual, and Hormonal. Response options for each EPIC item form a Likert scale, and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better QOL. |
Countries
Netherlands
Contacts
Primary ContactPim van Leeuwen, MD, PhD
Backup ContactLotte Zuur, MD
Outcome results
None listed