The purpose of this study is to evaluate the effectiveness of four of the nowadays most established primary treatments for patients with clinically localized prostate cancer (active surveillance, robot-assisted radical prostatectomy, intensity-modulated radiotherapy, and real-time brachytherapy) at short-, mid- and long-term follow-up. The primary aim is assessing the impact of treatments' side effects on patient's quality of life. As secondary objectives, biochemical disease-free survival, overall survival, and prostate cancer-specific survival will also be assessed.

Primary Objective:

To compare the impact of active surveillance, robot-assisted radical prostatectomy, intensity-modulated radiotherapy, and real-time brachytherapy in patients with localized prostate cancer, in Patient-Reported Outcome Measures, considering side effects and physical and mental health at short-, mid- and long-term follow-up.

Secondary Objectives:

To assess biochemical disease-free survival by treatment and risk group, at mid- and long-term follow-up.

To assess overall survival by treatment and risk group, at mid- and long-term follow-up.

To assess prostate cancer-specific survival by treatment and risk group, at mid- and long-term follow-up.

To assess perceived general health and cancer-specific quality of life by treatment and risk group, at short-, mid- and long-term follow-up.

To assess benefits and risks of the new treatment modalities for localized prostate cancer, compared with the traditional ones (open radical prostatectomy, external-beam radiotherapy and intersticial pre-planned brachytherapy).

To assess utilities with direct and indirect methods.

Outline:

This is a prospective observational study of a cohort with clinically localized prostate cancer treated with either active surveillance, robot-assisted radical prostatectomy, intensity-modulated radiotherapy, or real-time brachytherapy.

Participants are consecutively recruited in 18 Spanish hospital departments (located in six autonomous communities). Patients eligible for inclusion were: age 50-75, tumor stage T1c or T2a, N0 and M0; Gleason ≤ 6 (or 3+4 if T1c); Prostate Specific Antigen (PSA) ≤ 10 ng/mL; and to be treated with active surveillance, robot-assisted radical prostatectomy, intensity-modulated radiotherapy, or real-time brachytherapy. Patients were excluded when body mass index was >33, they had undergone neoadjuvant hormonal treatment, previous pelvic treatments, and/or had presence of serious comorbidities. The decision regarding treatment is made jointly by patients and health professionals.

Demographic and clinical characteristics at baseline are recorded at clinical sites and include age, PSA, Gleason score, prostate volume, risk group and use of adjuvant hormonal treatment. According to the national health guidelines, participants will be visited every 6-12 months after treatment, and at least annualy thereafter.

Quality of Life questionnaires are administered centrally by telephone interview before treatment and during follow-up at 1, 3, 6, and 12 months after treatment the first year, and annually thereafter. Quality of Life evaluations are gathered using computer-assisted telephone administration and include: (1) the Expanded Prostate cancer Index Composite (EPIC), specifically designed to measure the impact of the different treatments; (2) 36-item Short-Form Health Survey version 2 (SF-36v2); (3) the EuroQol-5 Dimension (EQ-5D-5L); and (4) the Patient-Oriented Prostate Utility Scale (PORPUS).

The sample size calculated to detect small differences between groups (0.3 SD) on the EPIC or SF-36v2 scores was of 90 patients per treatment group, given a statistical power of at least 80% at a significance level of 5%, and loss to follow-up of 10%.

Inclusion Criteria:

• Age between 50 and 75 years.
• Clinical stage T1 or T2, N0/Nx and M0/Mx.
• Gleason ≤6 or 7 (if 3+4 with T1c).
• Prostate-Specific Antigen (PSA) ≤ 10 .
• To be treated with active surveillance, robot-assisted radical prostatectomy, intensity-modulated radiotherapy or real-time brachytherapy

Exclusion Criteria:

• Body mass index > 33.
• Neoadjuvant hormonal treatment.
• Previous pelvic treatments.
• Presence of serious comorbidities.

Patients with clinically localized prostate cancer.

Data processing complies with ethical principles and relevant national and international legislation (Reglamento General de Protección de Datos 2016/679 and Organic Law 3/2018, of December 5). The final data will only be accessible to people working on the study. No data used in the analyses and subsequent dissemination of the study results will contain any identifiable reference referring to the names of patients. Once the study is finished, the results will be communicated to the competent authorities, in accordance with local legislation.

Data and associated documentation will be made available to users only under a data sharing agreement that provides for:

• A commitment to use the data only for research purposes and not to identify any individual participant;
• A commitment to protect data through the use of appropiate information technology;
• A commitment to destroy or return the data after analyses are complete.

The data and definitive documentation of the project will be stored centrally on virtual servers (up to 40 TB) and research storage infrastructures provided by the Hospital del Mar Medical Research Institute, during the lifetime of the projects. Thereafter, the data will be kept for the recommended period of 20 years, as set out in the Medical Research Council's guideline "Personal Information in Medical Research" (section 7).

Data sharing agreement among institutions.