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The Role of PSA in the Radiotherapy of Prostate Cancer

The Role of PSA in the Radiotherapy of Prostate Cancer

Radical radiation therapy and radical prostatectomy are the two most commonly employed therapeutic alternatives for clinically localized (T1-T2,NX,M0) prostate cancer. A vigorous debate is ongoing about the relative efficacy of each modality. This debate centers around the percentage of patients who cannot be cured by one method or the other, suggesting that some patients may be better served by one treatment, or by some form of combined-modality therapy employing radiation after surgery or neoadjuvant androgen suppression before radiation.

Dr. Roach attempts to define those patients with stage T1-T2 tumors (a heterogeneous group) who are most likely to be cured by radiation therapy. He critically reviews an early end point of failure, the serum prostate-specific antigen (PSA) value, which is being sought to assess more rapidly failure following the many therapies available to men with localized prostate cancer. As he points out, a rising PSA is a good measure of failure of either radiation or surgery to eradicate the tumor. However, it is still unclear as to whether this end point has an impact on the subsequent well-being of the patient, or whether or not PSA failure reliably predicts death from prostate cancer.

The only truly valid, unequivocal clinical end points of treatment efficacy for prostate cancer are overall survival, cancer-specific survival, and freedom from symptomatic failure. It has proved difficult to demonstrate any overall survival advantage from treatment of men who are diagnosed in their 60s or 70s with a disease that may be protracted over decades. The significant competing mortality in this age group is 3% per year, and thus, overall survival among prostate cancer patients may only be marginally improved, even if their therapy is 100% effective [1].

Cancer-specific survival, which scores the likelihood of death from cancer if a man does not die of another cause, is a better measure of treatment efficacy, but unfortunately more than 10 years of follow-up are required to obtain results. Thus, surrogate end points, such as PSA failure (as reviewed by Dr. Roach), prostate rebiopsy, anastomotic rebiopsy after radical prostatectomy, and the need for further treatment following initial therapy, have been used in large retrospective analyses of outcome [1-8].

In fact, both radical radiation therapy and radical prostatectomy are associated with relatively high rates of failure for some categories of tumors, and, in such cases, both are clearly insufficient therapy [9]. Based on the information presented in Dr. Roach's Table 3, we can make some progress in defining those patients within the rather heterogeneous stage Tl-T2 group who are most likely to be cured by radical radiation therapy as monotherapy; namely, men with stage T1-T2a,NX prostate cancer and serum PSA values of less than 10 ng/mL. Patients with stage T2b or higher disease and those with initial PSA values in excess of 10 ng/mL may benefit from conventional radiation therapy in terms of local control but are unlikely to be cured. Such patients may be better served by more modern approaches, such as conformal radiation therapy with radiation dose escalation, or by protocols combining androgen suppression with radiation therapy.

Finally, because there is a relatively higher incidence of failure following radical prostatectomy than was previously appreciated [6-8], appropriate follow-up cancer treatments after radical prostatectomy require further evaluation. Such investigations are underway in this country under the sponsorship of the Clinical Investigations Branch of the National Cancer Institute.

References

1. Barry MJ, Fleming C, Coley CM, et al: Should Medicare provide reimbursement for prostate specific antigen testing for early detection of prostate cancer? Part 1: Framing the debate. Urology 46:2-13, 1995.

2. Scardino PT, Wheeler TM: Local control of prostate cancer with radiotherapy: Frequency and prognostic significance of positive results of post-irradiation prostate biopsy. Natl Cancer Inst Monogr 7:95-103, 1988.

3. Kuban DA, El-Mahdi AM, Scheilhammer P: The significance of post-irradiation prostate biopsy with long-term follow-up (abstract). Int J Radiat Oncol Biol Phys 21(suppl 1):191, 1991.

4. Crook J, Robertson S, Collin G, et al: Clinical relevance of transrectal ultrasound, biopsy, and serum PSA following external beam radiotherapy for carcinoma of the prostate. Int J Radiat Oncol Biol Phys 27:31-37, 1993.

5. Connolly JR, Sinohara K, Presti JC, et al: Local recurrence after radical prostatectomy, characteristics in size, location and relationship to PSA and surgical margins. Urology 47:225-231, 1996.

6. Fowler FJ Jr., Barry MJ, Lu-Yao G, et al: Patient-reported complications and follow up treatment following radical prostatectomy: The national medicare experience. Urology 42:622-629, 1993.

7. Lu-Yao GL, Potosky AL, Albertson PC, et al: Follow-up prostate cancer treatments after radical prostatectomy: A population-based study. J Natl Cancer Inst 88:166-173, 1996.

8. Fowler FJ Jr., Barry MJ, Lu-Yao G, et al: Outcomes of external beam radiation therapy for prostate cancer: A study of medicare beneficiaries in three SEER areas. J Clin Oncol, 1996 (in press).

9. Zietman AL, Shipley WU, Coen JJ: Radical prostatectomy and radical radiation therapy for clinical T1-2 adenocarcinoma of the prostate: New insights into outcome from rebiopsy and PSA follow-up. J Urol 152:1806-1812, 1994.


 
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