Defining a new threshold for PSA outcomes in untreated prostate cancer.

4587 Background: To assess the relationship between tumor burden and sensitivity to hormonal therapy, we evaluated post-therapy PSA changes in patients in the rising PSA state (Scher et al, Urol 2000) and in patients with clinical metastases: non-castrate disease. The objective was to determine the proportion that achieved an undetectable PSA following treatment. METHODS: We identified 473 patients who experienced a rising PSA following local therapy from two available databases at MSKCC. The first database was a series of 233 patients enrolled on vaccine trials between 1995-200; the second was a series of 2652 patients undergoing prostatectomy at MSKCC from 1996-2002. One hundred forty-one patients were initiated on hormonal therapy with CAB, an antiandrogen alone or a GNRH analogue alone, between 1/93 and 6/03. As their primary therapy, 34 received radiation and 106 received radical prostatectomy. Sixty-eight were in a rising PSA clinical state and 73 had non-castrate metastatic disease. RESULTS: A greater number of patients with a rising PSA only achieved an undetectable PSA compared with metastatic patients (57 vs 38%, p=0.03). Rising PSA only patients: Age, Gleason grade, and doubling time did not predict for an undetectable PSA. Achievement of an undetectable PSA was statistically associated with prior prostatectomy, treatment with a GNRH analogue, a lower pretreatment PSA and a shorter time interval from local therapy (p<0.05). Metastatic patients: Achievement of an undetectable PSA was not associated with prior prostatectomy, treatment with a GNRH or the time interval from local therapy. A lower pretreatment PSA and shorter PSA doubling time were statistically associated with an undetectable PSA (p<0.05). Patients with metastatic disease and a detectable PSA nadir were more likely to exhibit progression of disease on imaging with follow-up (p=0.01). CONCLUSIONS: The rate of achieving an undetectable PSA with hormonal therapy is dependent upon the pretreatment PSA and the presence of metastatic disease. Achievement of an undetectable PSA is associated with a delay of disease progression on imaging in metastatic patients. Support: MSKCC SPORE P50 CA 92629-01; Koch Foundation No significant financial relationships to disclose.