The development of risk groups in men with metastatic castration-resistant prostate cancer based on risk factors for PSA decline

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Eur J Cancer.. [Epub ahead of print]
The
development of risk groups in men with metastatic castration-resistant
prostate cancer based on risk factors for PSA decline and survival.

Armstrong AJ, Tannock IF, Wit RD, George DJ, Eisenberger M, Halabi S.
Duke
Comprehensive Cancer Center and the Duke Prostate Center, Divisions of
Medical Oncology and Urology, Departments of Medicine and Surgery, DUMC
Box 102002, Durham, NC 27715, USA.

AIMS
OF THE STUDY:
There are no known predictive factors of response in men
receiving chemotherapy for metastatic castration-resistant prostate
cancer (mCRPC). We investigated pre-treatment factors that predicted a
30% PSA decline (30% PSAD) within 3 months of starting chemotherapy,
and assessed performance of a risk group classification in predicting
PSA declines and overall survival (OS) in men with mCRPC.
METHODS: In
TAX327, 1006 men with mCRPC were randomized to receive docetaxel (D) in
two schedules, or mitoxantrone (M), each with prednisone: 989 provided
data on PSA decline within 3 months. Predictive factors for a 30% PSAD
were identified using multivariable regression in D-treated men (n=656)
and validated in M-treated men (n=333). RESULTS: Four independent risk
factors predicted 30% PSAD: pain, visceral metastases, anaemia and bone
scan progression. Risk groups (good: 0-1 factors, intermediate: 2
factors and poor: 3-4 factors) were developed with median OS of 25.7,
18.7 and 12.8 months (p<0.0001); 30% PSAD in 78%, 66% and 58% of men
(p<0.001); and measurable disease response in 19%, 9% and 5% of men
(p=0.018), respectively. In the validation cohort, similar predictive
ability was noted for 30% PSAD, tumour response and OS. PCWG2 subtypes
were also predictive but resulted in unequal grouping. C-indices were
0.59 and 0.62 for 30% PSAD and OS in the validation dataset,
respectively. CONCLUSIONS: Risk groups have been identified and
validated that predict PSAD and OS in men with mCRPC and may facilitate
evaluation of new systemic regimens warranting definitive testing in
comparison with docetaxel and prednisone. Prospective validation of
this classification system is needed.