Evaluating the Impact of Prostate Only Versus Pelvic Radiation for N+ Prostate Cancer. (PROPER)

The N+-PROPER Trial: Evaluating the Impact of Prostate Only Versus Pelvic Radiation for N+ Prostate Cancer.

At least 40% of the patients with prostate cancer (PC) present with positive lymph nodes (N1). The optimal treatment strategy for these patients remains controversial. Although androgen deprivation therapy (ADT) is still often initiated as only treatment, the results are disappointing. Recent studies support the use of more aggressive therapies including external beam radiotherapy (EBRT) and ADT. The retrospective studies supporting the additional use of EBRT in N1 PC patients are however not conclusive regarding to the extent of radiation field.

Even after an EPLND, there might be a role for pelvic EBRT in irradicating microscopic disease. However pelvic irradiation irrevocably results in increased toxicity. Moreover, in node negative (N0) PC patients the addition of pelvic EBRT has not resulted in improved outcome in randomised trials. However in the setting of Tumor Node Metastasis pathological stage (p)N1, proven on pathological examination, PC patients this has never been evaluated so far. This trial aims to answer the question whether or not pelvic EBRT is beneficial in pathological N1 PC patients. It is also important to realise that not all pathological N1 PC patients have similar outcome. There is a significant impact of number of positive lymph nodes on outcome, with two positive nodes being suggested as a significant cut-off value in predicting survival in pathological N1 PC patients. By stratifying the patients according to the number of lymph nodes involved this study will add to the proper selection of those patients who will benefit most of pelvic EBRT and avoid toxicity in patients who have no benefit of pelvic EBRT.

Additionally, small RNAs constitute potentially valuable markers for the diagnosis, prognosis, and therapeutic choices in PC patients. Blood samples will be collected to examine the potential role of miRNAs as a biomarker and to develop a prognostic signature for clinical relapse-free survival.

The results of this trial will serve as a base for developping new trials in order to optimise the treatment of patients with pathological N1 PC.

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer
• Intervention / Treatment: Radiation: radiotherapy

Detailed Description

In an era with increasing evidence in favour of an aggressive local treatment, where an extended pelvic lymph node dissection (EPLND) is more frequently performed and with data supporting the potential role for external beam radiotherapy (EBRT) in pelvic node positive (N1) prostate cancer (PC), the treatment of N1 PC patients needs to be revised. Seen the lack of clear guidelines regarding the extent of radiation field in N1 prostate cancer patients, there is an urgent need for studies evaluating the place of pelvic EBRT.

The aim of this trial is thus to evaluate if pelvic irradiation has an impact on clinical relapse free survival in pathological N1 PC.

The hypothesis is that performing a pelvic EBRT after EPLND in pathological N1 PC patients results in a significant improved clinical relapse free survival with 15% when compared to prostate only EBRT.

This will be evaluated in a multicentre Phase III stratified randomised trial randomising patients with PC and 1-4 positive lymph nodes on EPLND between prostate(bed) only radiotherapy + 2 years of ADT or pelvic radiotherapy + 2 years of androgen deprivation. A total of 330 patients will be enrolled in this trial. Stratification is based on the number of positive lymph nodes since patients with increased number of positive lymph nodes exhibit a poorer prognosis.

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Ghent, Belgium, 9000
    • Ghent University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Histological proven carcinoma of the prostate
• Positive lymph nodes found on extended pelvic dissection (EPLND) defined as:
• Removal of the lymphatic tissue in the obturator fossa + along the external iliac vessels + additional complete resection of the lymph nodes (lnn) along, medially and laterally to, the hypogastric vessels
• If technically feasible: removal of lnn along the common iliac vessels
• Removal of ≥10 lnn
• Treatment of the primary tumor by either radical prostatectomy or EBRT
• Willing to receive androgen deprivation therapy
• World health organization 0-2
• Written informed consent

Exclusion Criteria:• >4 positive lnn found on EPLND

• Prior pelvic irradiation
• Other primary tumor (except for non-melanoma skin tumors) diagnosed <5 years before enrollment
• Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prostate(bed) only; external beam radiotherapy limited to the prostate(bed)	Radiation: radiotherapy; high dose external beam radiotherapy limited to the prostate(bed)
Active Comparator: Prostate(bed) and pelvis; external beam radiotherapy to the prostate(bed) and pelvic lymph node regions	Radiation: radiotherapy; high dose external beam radiotherapy limited to the prostate(bed)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of number of participants without clinical relapse	presence of loco(regional) release or distant metastases	8 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of number of participants experiencing Radiation Therapy Oncology Group toxicity	acute	5 years
Assessment of number of participants experiencing Radiation Therapy Oncology Group toxicity	late	10 years
Assessment of number of participants with biochemical control	absence of prostate specific antigen relapse	8 years

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Investigators: Principal Investigator: Valérie Fonteyne, Prof, University Hospital, Ghent

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): July 1, 2021
• Study Completion (Actual): September 22, 2022

Study Registration Dates

• First Submitted: April 15, 2016
• First Submitted That Met QC Criteria: April 15, 2016
• First Posted (Estimate): April 20, 2016

Study Record Updates

• Last Update Posted (Actual): December 28, 2022
• Last Update Submitted That Met QC Criteria: December 23, 2022
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 2016/0246

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided