Observation or Radical Treatment in Patients With Prostate Cancer

A Phase III Study of Active Surveillance Therapy Against Radical Treatment in Patients Diagnosed With Favourable Risk Prostate Cancer [START]

RATIONALE: Sometimes prostate tumours may not need treatment until they progress. In this case, observation may be sufficient. Radical treatments, such as radical prostatectomy or radiation therapy, may be effective in treating prostate cancer when it is first diagnosed. It is not yet known whether active surveillance is more effective than radical treatment as an initial intervention in favorable prognosis prostate cancer.

PURPOSE: This randomized phase III trial is studying active surveillance to see how well it works compared with radical treatment as an initial intervention in patients with favorable prognosis prostate cancer.

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer
• Intervention / Treatment: Procedure: conventional surgery; Radiation: brachytherapy; Radiation: external beam radiation therapy; Procedure: Biopsies

Detailed Description

OBJECTIVES:

Primary

• To compare disease-specific survival of patients with favorable risk prostate cancer treated with radical prostatectomy or radical radiotherapy at the time of initial diagnosis vs active surveillance and selective intervention based on pre-specified biochemical, histological, or clinical progression criteria.

Secondary

• To compare overall survival, quality of life using the EPIC-26, RAND SF-12, and State-Trait Anxiety Inventory, distant disease-free survival, PSA relapse/progression after radical intervention, and initiation of androgen deprivation therapy between the two treatment arms.
• To determine the proportion of patients on the active surveillance arm who receive radical intervention for prostate cancer.
• To determine if PSA doubling-time prior to diagnosis predicts eventual outcome.
• To determine if molecular biomarkers predict outcome.

OUTLINE: This is a prospective, randomized, multicenter study. Patients are stratified by treatment center, ECOG performance status (0 vs 1 or 2), disease stage (T1 vs T2), baseline PSA value (ng/mL or μg/L) (< 5.0 vs ≥ 5.0 and ≤ 10.0), and age (< 65 years vs ≥ 65 years). Patients are randomized to 1 of 2 arms.

• Arm I: Patients undergo radical intervention (radical prostatectomy or radiotherapy [external-beam radiotherapy 5 days a week for 4-8 weeks; permanent prostate brachytherapy; or high-dose rate temporary brachytherapy], based on patient and physician preference).
• Arm II: Patients undergo active surveillance with radical intervention at the time one or more pre-specified criteria (biochemical progression, histologic/grade progression, and/or clinical progression) are met.

Quality of life is assessed by the EPIC-26, RAND SF-12, and State Anxiety Inventory at baseline, periodically during study treatment, and after completion of radical treatment.

After completion of radical treatment, patients are followed every 6 months.

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Clinical Research Unit at Vancouver Coastal
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, AIB 3V6
      • Dr. H. Bliss Murphy Cancer Centre
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • QEII Health Sciences Center
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Health Research Institute - General Division
    • Toronto, Ontario, Canada, M4N 3M5
      • Odette Cancer Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • Univ. Health Network-Princess Margaret Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • CHUM - Hopital Notre-Dame
    • Montreal, Quebec, Canada, H2W 1S6
      • McGill University - Dept. Oncology
    • Quebec City, Quebec, Canada, G1R 2J6
      • CHUQ-Pavillon Hotel-Dieu de Quebec
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre Hospitalier Universitaire de Sherbrooke
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre

Participation Criteria

Eligibility Criteria

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

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate

  • Diagnosed within 6 months prior to randomization

• Patient has been classified as favorable risk as defined by the following:

  • Clinical stage T1b, T1c, T2a, or T2b at the time of diagnosis
  • Clinical (diagnostic biopsy) Gleason score ≤ 6
  • PSA ≤ 10.0 ng/mL
• Physical examination, rectal examination, and transrectal ultrasound have been done within 6 months prior to randomization and radiographic studies, if indicated, are negative for metastasis
• Patient is a suitable candidate for radical prostatectomy or radiotherapy

PATIENT CHARACTERISTICS:

• ECOG performance status 0, 1, or 2
• Patient has a minimum life expectancy of > 10 years
• In centers participating in the quality of life component of the study, the patient is able (i.e., sufficiently fluent) and willing to complete the quality of life questionnaires in either English or French
• No history of other malignancies, except adequately treated non-melanoma skin cancer, adequately treated superficial bladder cancer, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years from study randomization

PRIOR CONCURRENT THERAPY:

• No previous treatment for prostate cancer, including surgery (excluding biopsy and TURP), radiotherapy, or androgen deprivation therapy for greater than 3 months
• No planned androgen therapy except in the context of radical therapy

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
No Intervention: Active Surveillance; Active surveillance with radical intervention at the time one or more of the following occur: Biochemical progression; Grade progression; Clinical progression
Active Comparator: Radical Intervention; Radical prostatectomy or radiotherapy based on patient and physician preference	Procedure: conventional surgery; Radical prostatectomy; Radiation: brachytherapy; high dose rate temporary seed implant; permanent seed implant.; Radiation: external beam radiation therapy; 3D conformal radiation therapy; intensity modulated radiation therapy.; Procedure: Biopsies; Periodic repeat biopsies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-specific Survival	Time from the date of randomization to the date of death due to prostate cancer.	5 years 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Time from randomization to the date of death due to any causes.	5 years 6 months

Collaborators and Investigators

• Sponsor: NCIC Clinical Trials Group
• Collaborators: National Cancer Institute (NCI); Eastern Cooperative Oncology Group; Institute of Cancer Research, United Kingdom; Cancer and Leukemia Group B; Radiation Therapy Oncology Group; SWOG Cancer Research Network
• Investigators: Study Chair: Ian M. Thompson, MD, The University of Texas Health Science Center at San Antonio; Study Chair: Adam S. Kibel, MD, Washington University Siteman Cancer Center; Study Chair: Martin G. Sanda, MD, Beth Israel Deaconess Medical Center; Study Chair: Richard Choo, M.D, Mayo Clinic; Study Chair: Chris Parker, M.D, Royal Marsden Hospital, Sulton, UK; Study Chair: Laurence H. Klotz, MD, Toronto Sunnybrook Regional Cancer Centre

Publications and helpful links

General Publications

• Fung-Kee-Fung SD, Porten SP, Meng MV, Kuettel M. The role of active surveillance in the management of prostate cancer. J Natl Compr Canc Netw. 2013 Feb 1;11(2):183-7. doi: 10.6004/jnccn.2013.0026.

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2007
• Primary Completion (Actual): December 31, 2011
• Study Completion (Actual): January 10, 2013

Study Registration Dates

• First Submitted: July 10, 2007
• First Submitted That Met QC Criteria: July 10, 2007
• First Posted (Estimated): July 11, 2007

Study Record Updates

• Last Update Posted (Actual): August 23, 2023
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: adenocarcinoma of the prostate; stage II prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: PR11; U10CA077202 (U.S. NIH Grant/Contract); CAN-NCIC-CTG-PR11 (Registry Identifier: PDQ); CALGB-140602 (Other Identifier: CALGB Assigned Trial Code); SWOG-PR11 (Other Identifier: SWOG Assigned Trial Code); CDR0000557348 (Other Identifier: PDQ); RTOG-0873 (Other Identifier: RTOG); ECOG-JPR.11 (Other Identifier: ECOG Assigned Trial Code); ICR-CTSU-ProSTART (Other Identifier: CTSU)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No