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Time to Detectable Metastatic Disease in Patients with Rising Prostate-Specific Antigen Values following Surgery or Radiation Therapy

Authors' Affiliations: Departments of ¹ Medicine and ² Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York

Requests for reprints: Susan F. Slovin, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021. Phone: 646-422-4470; Fax: 212-988-0701; E-mail: slovins{at}mskcc.org.

Purpose: To determine factors associated with the development of radiographic metastatic progression for patients with recurrent prostate cancer following surgery and/or radiation therapy with prostate-specific antigen (PSA) doubling times of <12 months.

Experimental Design: One hundred and forty-eight patients with rising PSA values after primary therapy and a PSA doubling time of <12 months enrolled on clinical protocols were followed and monitored at protocol-specified intervals with examinations, PSA determinations, and imaging studies that included a computed tomography or magnetic resonance imaging and bone scan until metastases were detected. Metastasis-free survival was estimated using the Kaplan-Meier method and factors predictive of progression-free survival were estimated using the proportional hazards model. A nomogram based on the Cox model was constructed.

Results: Metastatic events were documented in 74% (110 of 148) of patients during the follow-up period. The median progression-free survival was 19 months, with 3- and 5-year metastatic progression–free survival of 32% and 16%, respectively. T stage (P = 0.07) and Gleason grade (P = 0.006) at the time of diagnosis, PSA values at the time of protocol entry (P < 0.001), and PSA doubling time (P < 0.001) were associated with progression in univariate analysis. These were combined into a nomogram to assess risk for an individual patient.

Conclusions: Tumor characteristics at the time of diagnosis, PSA doubling time following relapse, and the PSA value at the time of the protocol are predictive of metastatic progression. Because the PSA value at the time of monitoring was predictive, early treatment to prevent metastatic progression is favored.

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