UTILITY OF PSA DOUBLING TIME IN FOLLOW-UP OF UNTREATED PATIENTS WITH LOCALIZED PROSTATE CANCER ANDREW J. STEPHENSON, ARMEN G. APRIKIAN, LUIS SOUHAMI, HASSAN BEHLOULI, AVRUM I. JACOBSON, LOUIS R. BE ´ GIN, AND SIMON TANGUAY ABSTRACT Objectives. To evaluate the prostate-specific antigen (PSA) changes and the ability of PSA doubling time (PSADT) to predict disease progression in untreated patients with clinically localized prostate cancer. Methods. A total of 104 patients with localized prostate cancer were followed up expectantly with serial PSA measurements and digital rectal examination (DRE). PSADT was calculated by linear regression analysis for the 94 patients who had a minimum of three PSA measurements and 12 months of follow-up. The median follow-up was 33 months. Of the 94 patients, 45 underwent repeat prostate biopsy to evaluate whether tumor progression occurred during the observation period. Results. Twenty-seven percent of patients had rapid PSADTs (less than 48 months). Only the presence of palpable disease on DRE correlated with a PSADT of less than 48 months (P 0.05). However, a PSADT of less than 120 months consistently correlated with disease progression on DRE and on repeat biopsy, as well as with the presence of clinically significant cancer. PSADT did not correlate with the Gleason score. Furthermore, patients with a PSADT of less than 48 months did not differ significantly from those with a PSADT of 48 to 120 months with regard to Gleason score, disease progression on DRE or on repeat biopsy, and the presence of significant cancer. Conclusions. A PSADT of less than 120 months correlates with disease progression. However, its clinical utility remains limited to identify patients at risk of disease progression reliably. UROLOGY 59: 652–656, 2002. © 2002, Elsevier Science Inc. A s a result of the increased prostate cancer de- tection through the use of prostate-specific an- tigen (PSA) testing, a stage migration with the de- tection of earlier disease has been observed. 1 However, early detection can also result in the in- creased detection of potentially insignificant tu- mors characterized by a low volume (less than 0.5 cm 3 ) and low grade (Gleason score less than 7). 2,3 If left untreated, some of these cancers would prob- ably not have an impact on the patient’s overall survival. Chodak et al. 4 demonstrated an equiva- lent long-term cancer-specific survival between treated and untreated patients with low-grade dis- ease. Although significant cancers were defined as tumors larger than 0.5 cm 3 , we still do not have the means to reliably identify patients with indolent cancers worthy of observation. 5 Watchful waiting may be an option for patients with suspected indolent tumors, provided the means are available to identify progressive disease while these cancers remain curable. PSA is a poten- tially useful marker for this purpose. Studies have shown that serum PSA levels correlate with tumor volume and pathologic stage. 6–8 In addition, a rapid PSA change (expressed as PSA velocity or PSA doubling time [PSADT]) was shown to corre- late with the presence of cancer, as well as with metastatic disease. 6 –10 Stable PSA levels have been observed for up to 9 years before clinically evident prostate cancer, followed by a transition to expo- nential PSA growth. 10 Rapid PSA changes may cor- respond with a period of rapid tumor growth. Like- Drs. Tanguay and Aprikian are supported by Fonds de la Recher- che en Sante ´ du Que ´bec. From the Departments of Surgery (Urology), Oncology, and Pathology, McGill University, Montreal, Quebec, Canada Reprint requests: Simon Tanguay, M.D., Montreal General Hospital, 1650 Cedar Avenue, L8-309, Montreal, Quebec H3G 1A4, Canada Submitted: January 25, 2001, accepted (with revisions): Janu- ary 2, 2002 RAPID COMMUNICATION © 2002, ELSEVIER SCIENCE INC. 0090-4295/02/$22.00 652 ALL RIGHTS RESERVED PII S0090-4295(02)01526-1