UROLOGICAL ONCOLOGY

Biochemical failure as single abnormality in patients with prostate cancer following radical treatment with external radiotherapy: follow-up without immediate treatment
Faria SL, Salah M, David M, Souhami L, Duclos M, Shenouda G, Deblois F, Janick C, Freeman CR
Department of Radio Oncology and Epidemiology of McGill University, Montreal General Hospital, Montreal, Quebec, Canada
Int Braz J Urol. 2004; 30: 289-95

• Introduction: Biochemical failure has been defined as 3 consecutive increases in PSA following curative treatment of prostate cancer. The appropriate management in such cases is controversial. The most usual treatment has been early introduction of hormones. Such patients will live for many years and hormone therapy causes important secondary effects and increases costs. The guideline in our Department of Radiotherapy has been to follow up, with no initial therapy, cases with low PSA and short PSA doubling time. The present study reports this experience.
• Materials and Methods: 528 patients with localized prostate cancer were treated by radical approach between 1992 and 1999, with external radiotherapy, with or without adjuvant hormone therapy. After a median follow-up of 77 months, there were 207 (39%) cases with biochemical failure, 78 of which were followed without therapy after the identification of biochemical failure. All of them were asymptomatic patients and had negative radiographic examinations or did not have imaging exams requested since they presented a favorable outcome. The follow-up included at least 2 annual visits with physical examination and PSA.
• Results: Of the 78 patients with biochemical failure followed without initial therapy, 7 died from other causes than prostate cancer and the remaining 71 cases were alive and asymptomatic in the last follow-up. Prognostic factors previous to radiotherapy such as stage and Gleason score were not considered when deciding for follow-up without initial therapy in these cases. The most significant aspects considered for this decision were low PSA value (median PSA on the last visit for the 78 cases was only 3.9 ng/mL) and a slow PSA doubling time (in the present experience the median PSA doubling time was 22.5 months).
• Conclusion: There seems to be space for expectant management, without initial hormone therapy, in patients with prostate cancer who present biochemical failure and are asymptomatic after radical external radiotherapy. This decision is important, since early introduction of hormones brings late effects and is expensive. Prospective and randomized studies are required to define this issue.
  
  
• Editorial Comment
  The issue of treatment for rising PSA after definitive therapy, either by external beam radiation therapy, the subject in this report, or by radical prostatectomy remains a critical dilemma in the management of patients with prostate cancer. It is critical because of the frequency of occurrence (in this report 39% of 528 patients), the lack of evidence-based medicine upon which to ground one’s decision, and the apprehension that is associated with serial PSA monitoring. As this report indicates, the therapy is often prompted by a “chicken switch” reaction. Until data is available, and it is unlikely that it will be in the foreseeable future, careful evaluation of prognostic variables as the authors describe, provide the therapist with at least a logical approach to triggering the switch to androgen deprivation. Pretreatment of Gleason score and PSA and post-treatment progression indicators as PSA level and doubling time currently provide the trigger for the delivery of androgen deprivation to those for whom it will benefit most and withhold it from those who are at sufficiently low risk that the morbidity consequence to the therapy equals or outweighs the benefits that androgen therapy could deliver. Clinical trials will provide the most useful and unbiased information.
  Some of the current Phase III trials addressing the issue of PSA recurrence are continuous vs intermittent androgen deprivation after irradiation (JPR7 – NCI, Canada); androgen deprivation and immediate vs delayed chemotherapy (RTOG, P0014), androgen deprivation ± thalidomide (NCI-00-C0080) and for patients with a rising PSA after androgen deprivation but without evidence of metastatic disease, a trial comparing second line hormone therapy (ketoconazol + hydrocortisone) to chemotherapy (docetaxel and estramustine – ECOG 1899).
  Other agents are being investigated to address the rising PSA; i.e. Provenge, Atrasantin (endothelin-A inhibitor), Avastin (angrogenesis inhibitor).

Dr. Paul F. Schellhammer
Program Director of the Virginia Prostate Center
Professor of Urology, Eastern Virginia Medical School
Norfolk, Virginia USA