Radiographic progression with nonrising PSA in metastatic castration-resistant prostate cancer: post hoc analysis of PREVAIL.
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Date
2017-06-01ICR Author
Author
Bryce, AH
Alumkal, JJ
Armstrong, A
Higano, CS
Iversen, P
Sternberg, CN
Rathkopf, D
Loriot, Y
de Bono, J
Tombal, B
Abhyankar, S
Lin, P
Krivoshik, A
Phung, D
Beer, TM
Type
Journal Article
Metadata
Show full item recordAbstract
BACKGROUND: Advanced prostate cancer is a phenotypically diverse disease that evolves through multiple clinical courses. PSA level is the most widely used parameter for disease monitoring, but it has well-recognized limitations. Unlike in clinical trials, in practice, clinicians may rely on PSA monitoring alone to determine disease status on therapy. This approach has not been adequately tested. METHODS: Chemotherapy-naive asymptomatic or mildly symptomatic men (n=872) with metastatic castration-resistant prostate cancer (mCRPC) who were treated with the androgen receptor inhibitor enzalutamide in the PREVAIL study were analyzed post hoc for rising versus nonrising PSA (empirically defined as >1.05 vs ⩽1.05 times the PSA level from 3 months earlier) at the time of radiographic progression. Clinical characteristics and disease outcomes were compared between the rising and nonrising PSA groups. RESULTS: Of 265 PREVAIL patients with radiographic progression and evaluable PSA levels on the enzalutamide arm, nearly one-quarter had a nonrising PSA. Median progression-free survival in this cohort was 8.3 months versus 11.1 months in the rising PSA cohort (hazard ratio 1.68; 95% confidence interval 1.26-2.23); overall survival was similar between the two groups, although less than half of patients in either group were still at risk at 24 months. Baseline clinical characteristics of the two groups were similar. CONCLUSIONS: Non-rising PSA at radiographic progression is a common phenomenon in mCRPC patients treated with enzalutamide. As restaging in advanced prostate cancer patients is often guided by increases in PSA levels, our results demonstrate that disease progression on enzalutamide can occur without rising PSA levels. Therefore, a disease monitoring strategy that includes imaging not entirely reliant on serial serum PSA measurement may more accurately identify disease progression.
Collections
Subject
Humans
Disease Progression
Phenylthiohydantoin
Prostate-Specific Antigen
Antineoplastic Agents
Disease-Free Survival
Treatment Outcome
Proportional Hazards Models
Drug Resistance, Neoplasm
Aged
Middle Aged
Male
Prostatic Neoplasms, Castration-Resistant
Research team
Prostate Cancer Targeted Therapy Group
Language
eng
Date accepted
2016-11-29
License start date
2017-06
Citation
Prostate cancer and prostatic diseases, 2017, 20 (2), pp. 221 - 227
Publisher
NATURE PUBLISHING GROUP