Clinical trial NCT03921996: Extended Pelvic Lymph Node Dissection vs. no Pelvic Lymph Node Dissection at Radical Prostatectomy for intermediate-and High-risk Prostate Cancer
Official title: Extended Pelvic Lymph Node Dissection vs. no Pelvic Lymph Node Dissection at Radical Prostatectomy for intermediate-and High-risk Prostate Cancer: An International, Multicenter, Randomized Phase III Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: Extended pelvic lymph node dissection
Pelvic lymph node dissection
ePLND
Prostate Cancer
intermediate prostate cancer
High-risk prostate cancer
Lead sponsor: Swiss Group for Clinical Cancer Research
Sponsor class: OTHER
First posted: 2019-04-19
Enrollment: 57
Sex: MALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: SAKK 09/18 is an international, multicenter, randomized, phase III surgical intervention trial
Primary purpose: TREATMENT

Brief summary: For patients with intermediate-risk prostate cancer plus a predicted risk of \>5% for positive lymph nodes and with high-risk prostate cancer, international guidelines recommend ePLND along with the RP. Besides an improved accuracy in staging, the therapeutic role of ePLND remains controversial. We hypothesize that ePLND prolongs time to biochemical recurrence (BCR) and prostate cancer-specific survival (PCSS) in intermediate- and high-risk PCa patients.

Detailed description: Radical prostatectomy (RP) is the surgical standard treatment for men with localized prostate cancer (PCa) and a life expectancy of \> 10 years. RP is a treatment option for localized PCa that shows benefit in prostate cancer-specific survival (PCSS) and overall survival compared to conservative management. According to the guideline recommendations of the European Association of Urology (EAU), RP should be accompanied by extended pelvic lymph node dissection (ePLND) in patients with intermediate-risk PCa (D'Amico classification) and \> 5% nomogram (Briganti) predicted risk of positive lymph nodes and in all high-risk PCa cases.

Besides an improved accuracy in staging, the therapeutic role of ePLND remains controversial. The primary goal of this trial is to provide high-level evidence regarding the therapeutic benefit of ePLND in intermediate- and high-risk PCa patients without clinical evidence of nodal involvement. It is hypothesized that ePLND prolongs time to biochemical recurrence (BCR) and prostate cancer-specific survival (PCSS) in intermediate- and high-risk PCa patients.

Eligibility criteria: Inclusion Criteria:

* Written informed consent according to ICH/GCP regulations before registration and prior to any trial specific procedures.
* Histologically proven localized adenocarcinoma of the prostate.
* High-risk prostate cancer or intermediate-risk prostate cancer defined by D'Amico classification system, with an estimated risk of \>5% of lymph node metastasis.
* Patients with a prior malignancy and treated with curative intention are eligible if all treatment of that malignancy was completed at least 2 years before registration and the patient has no evidence of disease at registration. Less than 2 years is acceptable for malignancies with low risk of recurrence and/or no late recurrence.
* Age ≥ 18 years and ≤ 80 years.
* WHO performance status 0-1.
* Adequate condition (ASA ≤ III) for general anesthesia and radical prostatectomy surgery.
* Baseline Quality of Life (QoL) questionnaires have been completed.

Exclusion criteria

* Any pre-operative evidence for T4 disease.
* Metastatic prostate cancer according to staging or evidence of lymph node metastasis by imaging, defined as any pelvic lymph node \>9 mm in the short axis or positive lymph nodes detected by imaging techniques with sensitivities similar or better than PSMA-PET or Choline-PET prior to surgery.
* PSA ≥ 50 ng/ml.
* Any prior neo-adjuvant, local or systemic treatment for prostate cancer (alpha reductase inhibitors for treatment of benign hyperplasia are allowed)
* Previous pelvic lymph node dissection.
* Any uncontrolled active systemic infection requiring intravenous (iv) antimicrobial treatment.
* Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.

Primary outcomes:
measure: Time to biochemical recurrence (BCR)
timeFrame: From the date of randomization until the date of biochemical recurrence, assessed up to 15 years after surgery
Secondary outcomes:
measure: Prostate-specific antigen (PSA) persistence
timeFrame: From the date of surgery to 14 weeks after surgery
measure: Time to initiation of adjuvant or salvage therapies
timeFrame: From the date of randomization until the date of start of any type of adjuvant or salvage therapy, assessed up to 15 years after surgery
measure: Time to loco-regional recurrence
timeFrame: From the date of randomization until the date of local or regional recurrence, assessed up to 15 years after surgery
measure: Time to distant metastasis
timeFrame: From the date of randomization until the date of first occurrence of distant metastasis, assessed up to 15 years after surgery
measure: Prostate cancer-specific survival (PCSS)
timeFrame: From the date of randomization until the date of death due to prostate cancer, assessed up to 15 years after surgery
measure: Overall survival (OS)
timeFrame: From the date of randomization until the date of death, assessed up to 15 years after surgery
measure: Intraoperative complications
timeFrame: During surgery
measure: Postoperative complications
timeFrame: From the date of surgery to 14 weeks after surgery
measure: Adverse events (AE)
timeFrame: From the date of registration to 15 years after surgery
Other outcomes:
Locations:
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau AG
city: Basel
country: Switzerland
facility: Universitätsspital Basel
city: Bern
country: Switzerland
facility: Inselspital, Bern
city: Chur
country: Switzerland
facility: Kantonsspital Graubuenden
city: Genève
country: Switzerland
facility: Hôpitaux Universitaires Genève
city: Liestal
country: Switzerland
facility: Kantonsspital Baselland
city: Luzern
country: Switzerland
facility: Luzerner Kantonsspital
city: Münsterlingen
country: Switzerland
facility: Spital Thurgau AG (Frauenfeld and Münsterlingen)
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
city: Zürich
country: Switzerland
facility: Stadtspital Triemli
city: Zürich
country: Switzerland
facility: Universitätsspital Zürich
Study officials:
affiliation: University Hospital Basel, Department of Urology
name: Cyrill A. Rentsch, MD-PhD
role: STUDY_CHAIR
References: