PSA Biochemical Response as Prognostic Factor in Metastatic Castration-Sensitive Prostate Cancer (PSA-DEEP02)

Evaluation of Biochemical Response as Prognostic Factor in Metastatic Castration-Sensitive Prostate Cancer and Analysis of Baseline Characteristics Between Patients With or Without PSA Value of 0.2 ng/dl.

Prostate cancer remains the most common malignancy in men in Europe. Over the last two decades, the treatment landscape for both localized and metastatic prostate cancer has been revolutionized. For patients with metastatic castration-sensitive prostate cancer (mCSPC), the primary treatment objectives are to delay progression to metastatic castration-resistant prostate cancer (mCRPC) and to improve overall survival (OS). Although patients with PC may initially respond to androgen deprivation therapy (ADT), progression to castration resistance occurs in 10-20% of patients within 5 years.

Primary ADT has been the standard of care for over 50 years. However, recent advancements have shifted treatment from ADT monotherapy for all mHSPC/mCRPC patients to more intensive approaches, which include combinations of ADT with new androgen receptor pathway inhibitors (ARPIs), chemotherapy, or both, tailored to tumor characteristics such as metastatic burden.

In clinical practice, a reduction in prostatic specific antigen (PSA) levels from baseline is commonly used to monitor disease control, particularly in the castration sensitive phase (both early and metastatic). For patients with mCSPC, a decrease in PSA levels signifies that the treatment is effective. Moreover, the depth, time and duration of this PSA reduction are linked to better clinical outcomes, including OS. Although more patients achieved an optimal PSA response with intensified ADT (with ARPI or docetaxel), those with a suboptimal response have a significantly worse survival rate. Several key studies have demonstrated that achieving undetectable PSA (≤0.2 ng/mL) is associated with better OS, irrespective of subgroups.

This study aims to evaluate patient survival based on PSA response and to describe baseline characteristics among patients with or without PSA response. Specifically, patients will be divided into two groups based on the achievement of PSA values ≤ 0.2 ng/dl, and overall survival (OS) and progression free survival (PFS) for each group will be evaluated. Clinical and laboratory information at baseline will be compared between the two groups. Baseline characteristics considered are histology, Gleason score, stage of disease, presence of genetic alterations, PSA values, sites and number of metastases, de novo or metachronous disease, high/low risk disease, high/low volume disease.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer; Metastatic Cancer; Castrate Sensitive Prostate Cancer
• Intervention / Treatment: Drug: Enzalutamide; Drug: Apalutamide (Erleada™) 60 mg or 240 mg tablets; Drug: Darolutamide (Nubeqa®) 300 mg tablets; Drug: Taxotere (docetaxel); Drug: Abiraterone acetate + Prednisone or Prednisolone

• Study Type: Observational
• Enrollment (Estimated): 152

Contacts and Locations

• Study Contact: Name: Roberto Iacovelli; Phone Number: +390630157373; Email: roberto.iacovelli@policlinicogemelli.it

Study Locations

• Italy
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Recruiting
      • Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC ONCOLOGIA MEDICA
      • Principal Investigator: Roberto Iacovelli
      • Contact: Roberto Iacovelli; Phone Number: +390630151; Email: roberto.iacovelli@policlinicogemelli.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients affected by metastatic castration sensitive prostate cancer who received the diagnosis from July 2022 treaded, and started androgen deprivation therapy plus one ARPI-based therapy.

Description

Inclusion Criteria:

• Aged ≥ 18 years old;
• Men with histologically or cytologically confirmed adenocarcinoma of the prostate with evidence of metastases;
• ECOG performance status ≤2;
• Staging of disease with TC + bone scintigraphy or with PET PSMA/choline;
• Availability of baseline PSA and after six months (±1) from the beginning of the ADT;
• Ongoing or completed treatment with at least one ARPI among abiraterone acetate, apalutamide, darolutamide and enzalutamide;
• Adequate information about baseline demographic, biological, clinical and laboratory data;
• Signed informed consent form, or declaration in lieu of informed consent form, if applicable.

Exclusion Criteria:

• Patients without evidence of histological diagnosis of prostate cancer;
• No follow up visit after the beginning of therapy;
• No availability of baseline informations.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the survival based on the PSA response at six months from the beginning of ARPI in patients with mCSPC.	To evaluate the overall survival (OS) between patients with or without a PSA response ≤0.2 ng/ml at six months (from the beginning of ADT) in patients with mCSPC.	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the efficacy of ARPI-based therapy based on the PSA response at six months from the beginning of ARPI in patients with mCSPC.	To evaluate the progression-free survival (PFS) between patients with or without a PSA response ≤0.2 ng/ml at six months (from the beginning of ADT).	4 years
To describe the baseline characteristics between patients with or without PSA response.	To describe the baseline clinical and biological characteristics between patients who achieved a PSA response ≤0.2 ng/ml at six months (from the beginning of ADT).	4 years
To describe the timing of PSA response	To describe the timing from the beginning of the ADT and the value ≤0.2 ng/dl among the responder patients.	4 years

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Principal Investigator: Roberto Iacovelli, Fondazione Policlinico Universitario A. Gemelli, IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): April 30, 2028

Study Registration Dates

• First Submitted: October 21, 2024
• First Submitted That Met QC Criteria: October 21, 2024
• First Posted (Actual): October 22, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 11, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Immune System Diseases; Prostatic Neoplasms; Hypersensitivity; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Enzyme Inhibitors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Steroid Synthesis Inhibitors; Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Docetaxel; Abiraterone Acetate; Prednisone; Prednisolone
• Other Study ID Numbers: 7039

Drug and device information, study documents

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