Tracer-Guided Surgery for Recurrent Prostate Cancer

Study Overview
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Brief Summary
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ADT with or without robot-assisted PSMA-radioguided surgery for patients with recurrent prostate cancer.

Detailed Description
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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.

Official Title
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Tracer-Based Image Guided Surgery for Recurrent Prostate Cancer: A Prospective Randomized Controlled Trial

Conditions
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Prostate Cancer

Intervention / Treatment
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* Procedure: PSMA-radioguided surgery
* Drug: ADT


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A: ADT<br>Patients in arm A will receive standard 6 months of ADT according to current clinical guidelines. | Drug: ADT<br>* 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.<br>|
| Experimental: Arm B: ADT + PSMA radioguided surgery<br>Patients in arm B will receive standard 6 months of ADT according to current clinical guidelines, and will undergo 99mTechnetium (99mTc)-based PSMA-radioguided salvage surgery. | Procedure: PSMA-radioguided surgery<br>* 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.<br>Drug: ADT<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical progression-free survival (CPFS) | 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 | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metastasis-free survival (MFS) | 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. | 24 months | 
| Biochemical progression-free survival (BPFS) | 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) | 24 months | 
| Castrate resistant prostate cancer (CRPC) | 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. | 10 years | 
| Overall survival (OS) | Overall survival will be read as the time from trial randomization to the date of death from any cause | 10 years | 
| Incidence of adjuvant therapy | ADT, radiation therapy or additional salvage surgery | 10 years | 
| Patient reported QOL as per EORTC-QLQ C30 | 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 | 24 months | 
| Patient reported QOL as per Expanded Prostate cancer Index Composite (EPIC) 26 | 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. | 24 months | 
| Complications | Assessment of 99mTc-PSMA-I&S injection-related as well as surgery-related complication rate according to Clavien-Dindo. | 30 and 90 days | 
| Number of in-field recurrences | Recurrence measured by use of PSMA PET/CT in the template of 99mTc-PSMA-radioguided surgery (RGS) supported salvage surgery | 24 months | 
| Specificity of 99mTc-PSMA RGS for salvage surgery for recurrent PC compared to histologic evaluation | In percentage | 30 days | 
| Sensitivity of 99mTc-PSMA RGS for salvage surgery for recurrent PC compared to histologic evaluation | In percentage | 30 days | 
| Positive Predictive Value of 99mTc-PSMA RGS for salvage surgery for recurrent PC compared to histologic evaluation | In percentage | 30 days | 
| Negative Predictive Value of 99mTc-PSMA RGS for salvage surgery for recurrent PC compared to histologic evaluation | In percentage | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PSMA-radioguided surgery, ADT, recurrent prostate cancer