Review articleThe management of PSA failure after radical radiotherapy for localized prostate cancer
Introduction
Prostate cancer is the second most common cause of cancer death among British men. With the increasing use of prostate-specific antigen (PSA) screening, the incidence of prostate cancer is set to rise further. If American trends are followed, the number of new cases of prostate cancer in Britain could increase over the next decade to as many as 45 000–60 000 per year [10], with 15 000–20 000 of them receiving treatment with radical radiotherapy [21]. Disease recurrence after radiotherapy is well recognized. Formerly, the most common pattern of recurrence was with symptomatic metastatic disease and such men received palliative hormone therapy. Now that PSA testing is used as a routine part of follow-up after radical radiotherapy, an asymptomatic PSA rise is the most common form of failure. For example, in a recent report from M.D. Anderson of over 900 men irradiated in the PSA era, 265 (28%) had a rising PSA and just 41 (4%) had metastatic relapse at a median follow-up of 40 months [39]. There is at present no consensus regarding the management of PSA failure.
Treatment options for men with PSA failure following radiotherapy range from radical procedures, such as salvage prostatectomy, brachytherapy or cryotherapy, through immediate hormone therapy, to observation with delayed hormone therapy on symptomatic relapse. However, little is known about the efficacy of these management options because they have not been directly compared and because there is considerable uncertainty about the natural history of the untreated disease in this situation.
This review addresses the following questions concerning men with PSA failure after radical radiotherapy for clinically localized (T1–3,N0/Nx,M0) prostate cancer: what is the likely course of the disease?; is there a role for radical treatment?; what investigations should be performed?; should hormone therapy be given immediately, or delayed until clinical relapse?
Section snippets
Definition of PSA failure
Unlike after radical prostatectomy, the presence of a measurable serum PSA level after radical radiotherapy does not necessarily imply tumour recurrence. PSA levels may decline over a period of many months after radiotherapy and contrary to what one might expect the rate of decline is not a reliable prognostic indicator [29], [38]. The rate of PSA fall, and nadir level reached, may vary with the treatment method (external beam or brachytherapy) and with the delivered dose [2]. A variety of
Salvage prostatectomy after radical radiotherapy for localized prostate cancer
The case against the use of salvage prostatectomy for radiorecurrent disease rests on the technical difficulty of the procedure, its complication rate, and the lack of any proven benefit. The operation is technically more difficult than the standard radical prostatectomy, presumably because of the presence of radiation fibrosis and vascular effects. Operating times and hospital stays tend to be longer than with the standard procedure and transfusion requirements are higher [1], [5], [16], [17],
What investigations should be performed in men with PSA failure?
Thorough restaging is obviously required if the patient is a potential candidate for radical salvage therapy, and men with symptoms suggestive of recurrent disease also need to be investigated. For the remainder, which will comprise the majority, the need for restaging investigations is uncertain and there is a paucity of data on which to base a policy. In particular, it is not known whether the results of such investigations should influence the timing of hormonal therapy (see Section 5).
As
Should hormone therapy be given at the time of PSA failure, or delayed until clinical relapse?
Hormonal manipulation is the main therapeutic modality for the majority of men with PSA failure after radical radiotherapy. Standard options include GnRH (gonadotrophin releasing hormone) analogues or bilateral orchidectomy, with or without non-steroidal anti-androgens. A benefit for maximal androgen blockade has not yet been defined [28] and its use should still be subject to the mature results from randomized trials. Monotherapy with non-steroidal anti-androgens can be considered for men who
Suggested protocol for the management of PSA failure after radical radiotherapy
The available evidence does not allow firm recommendations to be made regarding the management of PSA failure after radical radiotherapy. The protocol shown in Fig. 1 is presented in the hope that it will stimulate discussion. The selection of candidates for radical salvage therapy is based on the criteria of Rogers et al. [30], but with the addition of PSA failure characteristics to reduce the probability of occult metastatic disease. In the absence of firm evidence-based recommendations,
Acknowledgements
This work was also supported by the Institute of Cancer Research, the Bob Champion Trust and the Cancer Research Campaign.
References (39)
- et al.
Salvage surgery plus androgen deprivation for radioresistant prostatic adenocarcinoma
J. Urol.
(1992) - et al.
Short-term outcomes after cryosurgical ablation of the prostate in men with recurrent prostate carcinoma following radiation therapy
Urology
(1995) - et al.
Radical prostatectomy after radiotherapy for prostatic cancer
J. Urol.
(1980) - et al.
Percutaneous cryoablation of the prostate: preliminary results after 95 procedures
J. Urol.
(1995) Radiotherapy for prostate cancer: the changing scene
Clin. Oncol.
(1995)- et al.
Combined orchiectomy and external radiotherapy versus radiotherapy alone for nonmetastatic prostate cancer with or without pelvic lymph node involvement: a prospective randomized study
J. Urol.
(1998) - et al.
Dose escalation with 3D conformal treatment: five year outcomes, treatment optimization and future directions
Int. J. Radiat. Oncol. Biol. Phys.
(1998) - et al.
Critical evaluation of salvage surgery for radio-recurrent/resistant prostate cancer
J. Urol.
(1995) - et al.
Radical prostatectomy after definitive radiation therapy for prostate cancer
Urology
(1991) - et al.
Ablation of tissue volumes using high intensity focused ultrasound
Ultrasound Med. Biol.
(1996)