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INTRODUCTION

Widespread use of prostate-specific antigen (PSA) testing has led to an increase in the number of men being diagnosed with prostate cancer and stage-shift towards earlier stage disease. PSA testing is also used extensively for monitoring of patients during follow-up. Within 10 years of radical treatment with either prostatectomy or radiotherapy, 20–40% of men are reported have a biochemical recurrence [1]. Identifying biochemical relapse can present a clinical dilemma as there remains considerable debate as to what threshold of PSA represents true biochemical recurrence in the context of alternative primary treatment regimens. Furthermore, ultrasensitive assays may be used providing measurements to 0.01 ng/ml or below and giving rise to false-positives [2]. Any rising level of PSA can cause patient anxiety even if currently recommended thresholds for biochemical relapse have not been exceeded.

There are many factors that need to be taken into consideration when a patient has developed biochemical relapse. Performance status and comorbidities influence treatment options. Besides total PSA, PSA kinetics may be determined such as time to PSA relapse, PSA velocity and PSA doubling time (PSADT). It is important to establish whether or not there is clinically detectable local and/or systemic disease, as this will also influence treatment recommendations. Staging investigations may include repeat prostate biopsies, bone scan, magnetic resonance imaging (MRI) of the pelvis and computed tomography (CT) of the abdomen and pelvis. The range of salvage treatments available and their profile of side-effects must be considered and discussed with the patient, as the patient’s preference will play an important part in the decision-making process.

The management and treatment strategies for biochemical recurrence of prostate cancer are complex. This chapter will review the definitions of biochemical relapse, natural history, diagnosis and management options available for a variety of different clinical settings of biochemical PSA relapse.

DEFINITION OF BIOCHEMICAL RELAPSE

Various definitions of biochemical relapse have been proposed for each definitive treatment. Validating a suitable threshold that represents true biochemical relapse is important to permit timing of appropriate treatment, to avoid undue distress to the patient and to avoid overtreatment. Uniformity of definitions would also allow comparisons among different institutions and different treatment modalities. Summaries of the key issues are reviewed following primary surgical and radiotherapy treatments.

PSA RECURRENCE AFTER RADICAL PROSTATECTOMY

Following successful radical prostatectomy, serum PSA should fall to undetectable levels within 1 month [3]. A large number of laboratories currently utilize PSA assays that can detect levels as low as 0.01 ng/ml. Any detectable levels of PSA (defined as greater than 0.01 ng/ml) could be falsely construed as residual malignant prostatic tissue or relapse were it not for the large disparity between this finding and the progression to clinical disease. Some patients in whom PSA remains detectable after radical prostatectomy do not experience a continuing increase in PSA. In this situation, ...

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