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Published on: March 6, 2018
Best therapeutic approach in metastatic hormone-sensitive prostate cancer based on disease volume: a systematic
Fabrizio Di Costanzo1,2, Chiara Mercinelli3,4, Alessio Signori5,6
1Department of Medical Oncology, Università degli Studi di Napoli Federico II, Naples, Italy.
Context:
With new treatment strategies approved in metastatic hormone-sensitive prostate cancer (mHSPC), heterogeneity across trials hinders the physicians' choice for first-line treatment.
Objective:
We conducted a systematic review and network meta-analysis to assess the efficacy of currently approved treatments for mHSPC stratifying patients according to their disease burden (high- vs. low-volume as per CHAARTED criteria) and onset of metastatic disease (synchronous vs. metachronous).
Intervention:
Eleven randomized controlled trials (RCTs) published until October 30, 2024 were included. Treatment regimens were grouped as triplets for combinations of docetaxel, androgen receptor pathway inhibitors (ARPIs) and androgen-deprivation therapy (ADT), separate doublets for docetaxel plus ADT, ARPI plus ADT, or monotherapy for ADT alone.
Outcome Measurements And Statistical Analysis:
Overall survival (OS) and radiographic progression-free survival (rPFS) outcomes were collected. OS as primary endpoint, and rPFS as secondary endpoint, were analyzed separately in high- and low-volume patients. Additional subgroup analyses accounted for timing of metastases categorized as high-volume/synchronous, high-volume/metachronous, low-volume/synchronous, and low-volume/metachronous disease.
Evidence Synthesis:
Triplet combinations prolonged significantly OS and rPFS in high-volume disease (P-score 0.99), and high-volume/synchronous disease (P-score 0.99). ARPI/ADT doublets performed best in low-volume patients (P-score 0.94), and low-volume/metachronous (P-score 0.99). In the high-volume/metachronous population, triplets, and doublets were equally effective.
Conclusions:
The results provide collective evidence for treatment selection based on disease volume and timing of metastasis with strongest survival benefits of triplets for high-volume/synchronous mHSPC patients and of ARPI doublets for low-volume disease.
Insights
Triplet combinations offer the best survival benefits for high-volume metastatic hormone-sensitive prostate cancer (mHSPC). Androgen receptor pathway inhibitor (ARPI) doublets are most effective for low-volume mHSPC, guiding first-line treatment choices.
Area of Science:
- Oncology
- Clinical Trials
- Prostate Cancer Research
Background:
- Metastatic hormone-sensitive prostate cancer (mHSPC) presents treatment heterogeneity.
- Physicians face challenges in selecting first-line therapy due to diverse trial outcomes.
Purpose of the Study:
- To systematically review and network meta-analyze approved mHSPC treatments.
- To stratify treatment efficacy by disease burden (high- vs. low-volume) and metastatic onset (synchronous vs. metachronous).
Main Methods:
- Eleven randomized controlled trials (RCTs) published up to October 30th, 2024.
- Treatment regimens included Triplets (docetaxel, ARPIs, ADT), Doublets (docetaxel/ADT, ARPI/ADT), and Monotherapy (ADT).
- Overall survival (OS) and radiographic progression-free survival (rPFS) were analyzed across subgroups.
Main Results:
- Triplet combinations significantly improved OS and rPFS in high-volume and high-volume/synchronous mHSPC.
- ARPI/ADT doublets demonstrated superior outcomes in low-volume and low-volume/metachronous mHSPC.
- In high-volume/metachronous disease, triplets and doublets showed comparable efficacy.
Conclusions:
- Evidence supports mHSPC treatment selection based on disease volume and metastasis timing.
- Triplets provide the strongest survival benefits for high-volume/synchronous mHSPC.
- ARPI doublets are the preferred choice for low-volume mHSPC.
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