Early Endpoints in High-risk Localized Prostate Cancer: Exploratory Analysis of Three Radiation Therapy Oncology Group Phase 3 Studies.
Eur Urol
; 84(3): 331-340, 2023 09.
Article
en En
| MEDLINE
| ID: mdl-37393115
ABSTRACT
BACKGROUND:
Early endpoints in clinical trials of high-risk localized prostate cancer (HRLPC) that resemble those monitored in real-world practice could expedite clinical development.OBJECTIVE:
To assess the association of prostate-specific antigen (PSA) recurrence (PSA-R)-based early endpoints with metastasis-free survival (MFS), overall survival (OS), and prostate cancer (PC)-specific survival (PCSS), and to identify clinically undetectable disease. DESIGN, SETTING, ANDPARTICIPANTS:
A post hoc analysis of patients with HRLPC from Radiation Therapy Oncology Group studies 9202, 9902, and 0521 was performed. INTERVENTION Long-term adjuvant androgen-deprivation therapy (ADT) and post-primary definitive radiotherapy. OUTCOME MEASUREMENTS AND STATISTICALANALYSIS:
Event-free survival (EFS; PSA-R, locoregional recurrence [LRR], distant metastasis [DM], or death), biochemical failure (PSA-R), general clinical failure (PSA-R, LRR, DM, ADT initiation, or death), and no evidence of disease (NED; alive patients without PSA-R, LRR, DM, and subsequent PC therapy, and with testosterone recovery) were assessed for association with MFS, OS, and PCSS using correlation and landmark analyses, Kaplan-Meier method, and Cox proportional-hazard model. PSA-R was defined as PSA nadir + 2 ng/ml; PSA nadir + 2 ng/ml and rising; PSA >5, 10, and 25 ng/ml; or PSA doubling time (PSADT) <6 mo. RESULTS ANDLIMITATIONS:
Among assessed early endpoints, EFS with PSA nadir + 2 ng/ml and rising, or with PSA >5 ng/ml was associated with MFS, OS, and PCSS. No development of EFS with PSADT <6 mo or ADT initiation event or achievement of NED at 3 yr was associated with prolonged OS, MFS, and PCSS (hazard ratio [95% confidence interval], 0.53 [0.45-0.64], 0.63 [0.52-0.76], and 0.26 [0.18-0.36], or 0.56 [0.48-0.66], 0.62 [0.52-0.74], and 0.26 [0.19-0.37]) after the landmark time. Older studies performed before the current guidance should be interpreted with caution.CONCLUSIONS:
We identified EFS with PSA nadir + 2 ng/ml and rising, PSA >5 ng/ml, or PSADT <6 mo ± ADT initiation and NED as potentially promising early endpoints in HRLPC that should be validated further. PATIENTSUMMARY:
We identified novel clinical measures that may expedite the development of new medicines for patients with localized prostate cancer at a high risk of progression. These measures, which took into account prostate-specific antigen assessments and other clinical characteristics, should be confirmed in future studies. We also defined a novel measure of no evidence of disease that can help treating physicians identify patients with clinically undetectable disease.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
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Antígeno Prostático Específico
Tipo de estudio:
Etiology_studies
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Guideline
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Humans
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Male
Idioma:
En
Revista:
Eur Urol
Año:
2023
Tipo del documento:
Article