PSA Progression Postprostatectomy

Prostate Cancer

REVIEWING THE LITERATURE Prostate Cancer PSA Progression Postprostatectomy Herbert Lepor, MD New York University School of Medicine New York [Rev Urol. 2000;2(1):25] T he article by Pound and colleagues provides information related to the risk of biochemical failure following radical prostatectomy and the natural history of these men. This information is of great utility to both the physician weighing the pros and cons of initiating adjuvant therapy and the patient who desires a realistic appraisal of his life expectancy. This is a must-read study for all urologists who are involved in treating patients following prostatectomy. Natural History of Progression After PSA Elevation Following Radical Prostatectomy Pound CR, Partin AW, Eisenberger MA, et al. JAMA. 1999;281:1591-1597. In this study of 1,997 men who underwent radical prostatectomy, biochemical recurrence developed in 314. Three hundred five (97%) of this group did not receive hormonal therapy until there was clinical evidence of metastases. Of the men who experienced a biochemical failure, only 4% developed a biochemical recurrence after 10 years postprostatectomy. The 10- and 15-year metastases-free survival rates were 87% and 82%, respectively. For those men with low (2 to 4), intermediate (5 to 7), and high (8 to 10) Gleason scores, metastases-free survival at 10 years was 100%, 91%, and 43%, respectively. The Gleason score, time to prostate-specific antigen (PSA) recurrence, and PSA doubling time (PSADT) predicted the time course for the development of metastases in men with PSA recurrence following radical retropubic prostatectomy. Gleason scores of 5 to 7 versus 8 to 10, PSA recurrence at more than 2 years versus 2 years or less, and a PSADT of more than 10 months versus a PSADT of less than 10 months were the optimal parameters for determining the risk of metastases. Based on these clinical parameters, an algorithm was constructed that estimates the likelihood of remaining free of metastases. For example, a person with a Gleason score of 5 to 7 who develops a PSA recurrence at more than 2 years following radical prostatectomy and who has a PSADT of more than 10 months has an 82% (confidence interval 69% to 90%) probability of being metastases-free 7 years after the first evidence of biochemical failure. The wisdom of offering this person adjuvant hormonal therapy, with its associated short- and long-term complications and unproven survival advantage, must be questioned. This patient is also not a reasonable candidate for investigational agents because of the protracted natural history of the disease. Once metastases were diagnosed, the time to original biochemical failure, PSA level at the time of diagnosing the metastatic disease, and the Gleason score did not predict survival following initiation of hormonal therapy. The only parameter that predicted survival was the duration of time between the prostatectomy and the time to diagnosis of metastases. The only limitation of this study is that some patients who experience a biochemical recurrence have disease that is potentially curable by radiation therapy. The article states that 83 (27%) of the men with biochemical failure had undergone unsuccessful radiotherapy. The authors did not indicate how many men with biochemical failure were successfully treated with irradiation. If this is a significant proportion of the study population, then the present study has a selection bias for men with a greater propensity to develop metastases. In summary, this important study demonstrates that: • The overwhelming majority of men do not die of prostate cancer following radical prostatectomy. • Approximately 30% of men will develop biochemical failure following radical prostatectomy. • The development of metastases occurs many years after biochemical failure. • The time from radical prostatectomy to the development of metastases can be predicted based on the Gleason score, the time between radical prostatectomy and the development of biochemical failure, and the PSADT. ■ WINTER 2000 REVIEWS IN UROLOGY 25