The authors used the Veterans Health Administration electronic health record data (01/2007-08/2017) to conduct a retrospective longitudinal study in Veterans with nmCRPC. Patients with castrate testosterone levels (< 50 ng/dL) or continuous androgen deprivation therapy, a >25% rise in PSA from nadir and absolute increase of >2 ng/mL (index), and a prostate cancer diagnosis >12 months before index were selected. Patients were excluded if they had < 12 months of enrollment before or < 6 months after the index date, evidence of metastatic disease 12 months before index (defined based on diagnoses for metastatic disease, use of chemotherapy, immunotherapy, radiopharmaceuticals, or oral mCRPC therapy), or evidence of participation in a clinical trial (defined based on diagnosis codes or prescription for experimental therapies). PSA was measured in the 12 months before index, at index, and 6 months after index. Patients with similar PSA trajectories (PSA patterns over time) were grouped using group-based trajectory analysis. OS was assessed with a Cox proportional hazards model adjusted for baseline characteristics, PSA trajectory group, and a time-varying indicator for metastases.
As follows is the study flow diagram:
Among the 13,552 men included, the mean age was 76.4 (SD 9.4) years and most were white (66%). During a mean 36 months (SD 26) of follow up there were 6,552 (48%) deaths; the median OS was 47 months. Group-based trajectory analysis resulted in four PSA trajectory groups.
The Cox model showed that PSA trajectory group was a strong predictor of OS, as compared to Group 1 (n=213), patients in the other groups were more likely to die:
- Group 2 (n=6,558): HR 1.602, p < 0.001
- Group 3 (n=5,323): HR 1.716, p < 0.001
- Group 4 (n=1,458): HR 2.005, p < 0.00
Higher log PSA at baseline increased risk of death (HR 1.092, p < 0.001). Moreover, compared to patients without metastases, patients who eventually developed metastases were also more likely to die (HR 3.661, p < 0.001).
The strength of this study is the strong support of PSA trajectory in the M0 CPRC state being a strong predictor of subsequent outcomes, which may have clinical and trial design implications. In conclusion, this study of Veterans with nmCRPC showed that higher baseline PSA, PSA trajectory group, and development of metastases were associated with increased risk of death.
Presented by: Dominic Pilon, MA, Groupe d’Analyse, Ltee, Montreal, Canada
Written By: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University - Medical College of Georgia, @zklaassen_md at American Urological Association's 2019 Annual Meeting (AUA 2019), May 3 – 6, 2019 in Chicago, Illinois
References:
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2. Smith MR, Saad F, Chowdhury S, et al. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med 2018;378(15):1408-1418.
3. Fizazi K, Shore N, Tammela TL, et al. Darolutamide in nonmetastatic castration-resistant prostate cancer. N Engl J Med. 2019 Feb 14 [Epub ahead of print]