694 CROSS-CULTURAL VALIDATION OF A PROGNOSTIC TOOL: EXAMPLE OF THE LIMITATIONS OF THE KATTAN PREOPERATIVE NOMOGRAM AS A PREDICTOR OF PROSTATE CANCER RECURRENCE AFTER RADICAL PROSTATECTOMY

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Prostate stem cell antigen mRNA in peripheral blood as a potential predictor of biochemical recurrence after radical prostatectomy Joung J.Y., Han K.S., Cho K.S., Kim E.K., Choi M.K., Seo H.K., Chung J., Park W.S., Lee H.Y. National Cancer Center, Dept. of Urologic Oncology Clinic, Goyang, South Korea Introduction & Objectives: To determine whether the detection of prostate stem cell antigen (PSCA) mRNA in peripheral blood has predictive value for biochemical recurrence (BCR) after radical prostatectomy (RP) in patients with high-risk prostate cancer. Material & Methods: We prospectively enrolled the patients with high-risk prostate cancer that associated with any one of three risk factors: PSA ≥ 20ng/ml, biopsy Gleason score ≥ 8, or clinical stage ≥ T2c. To detect PSCA mRNA-bearing cells in the peripheral blood, the nested reverse transcriptase-polymerase chain reaction (RT-PCR) was employed. The relationship between RT-PCR PSCA results and BCR following RP was evaluated. Results: Seventy-one patients who underwent RP for high-risk prostate cancer were enrolled. Mean patient age was 62.1 years (range 49 to 80). Initial preoperative serum PSA levels ranged from 1.9 to 79.0 ng/mL (median: 26.5 ng/ mL). PSCA-mRNA was detected in 9 (12.7%) patients, i.e., 2 of 37 patients (5.4%) with ≤ cT2b disease and 7 of 34 patients (20.6%) with ≥ cT2c disease (P=0.077). During a median 23 months of follow-up (range, 3 to 41 months), BCR developed in 18 patients (25.4 %) and median time to BCR was 11 months (range, 3 to 21 months) following RP. Kaplan-Meier analysis showed a significant difference in recurrence-free actuarial probabilities for those positive and negative for PSCA (log rank P=0.017). Prognostic factors found to increase the risk of BCR by multivariate analysis using the Cox proportional hazard regression model were stage ≥ pT3 (HR, 5.38; 95%CI, 1.46-19.80; P=0.011) and RT-PCR PSCA positivity (HR, 5.76; 95%CI, 1.70-19.51; P=0.005). Conclusions: The detection of PSCA mRNA-bearing prostate cancer cells in the peripheral blood is a significant predictor of BCR after RP in high-risk prostate cancer.



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Cross-cultural validation of a prognostic tool: Example of the limitations of the kattan preoperative nomogram as a predictor of prostate cancer recurrence after radical prostatectomy Rouprêt M.1, Hupertan V.1, Comperat E.2, Drouin S.J.1, Phé V.1, Xylinas E.1, Sibony M.3, Bitker M.O.B.1, Chartier-Kastler E.1, Richard F.1, Cussenot O.4 Pitié Salpétrière Hospital, Dept. of Urology, Paris, France, 2Pitié Salpétrière Hospital, Dept. of Pathology, Paris, France, 3Tenon Hospital, Dept. of Pathology, Paris, France, 4Tenon Hospital, Dept. of Urology, Paris, France

1

Introduction & Objectives: To establish the predictive accuracy of the Kattan preoperative nomogram by comparing predictions at 5 years with actual recurrence in patients who underwent radical prostatectomy. Material & Methods: We reviewed the data for 928 patients treated by radical prostatectomy as first-line treatment of localized prostate cancer, between 1994 and 2005. Recurrence was defined as a single PSA measurement above 0.4 ng/ml. Five-year recurrence free survival (RFS) rate was evaluated on censured data by the Kaplan-Meier method. Relationships between all predictor variables included in the Kattan nomogram (PSA, biopsy Gleason scores, clinical stage) and survival were evaluated by Cox’ proportional hazards regression analysis. The discriminating ability of the nomogram was assessed by the concordance index (c-index). Bootstrapping was used to assess confidence intervals. Then, calibration was assessed. Results: Median follow-up was 60 months. Overall, 177 (19%) patients had experienced recurrence. Overall, the 5-year RFS rate was 80.9% (95% CI 0.78-0.83). Of the 3 variables included in the nomogram, all were associated with recurrence in a multivariate analysis (p<0.001). The c-index was only 0.664 (95% CI 0.5840.744). In general, the nomogram was not well calibrated. Conclusions: There was a discrepancy between predicted RFS as estimated by the Kattan nomogram and actual relapse in our population of patients. Clinicians should be aware that the nomogram is less accurate when used outside the geographic area where it has been formerly set. The cross-cultural validation of a prognostic tool is an important point that needs to be addressed.



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Decrease in ultrasensitive PSA after radical prostatectomy as the prognostic factor of biochemical recurrence of prostate cancer

Preoperative low serum testosterone levels are associated with tumor aggressiveness in radical prostatectomy treated cancer patients

Vesely S., Jarolim L., Kawaciuk I., Hanek P., Schmidt M.

Botto H.1, Andréou A.1, Ben Saddik A.1, Lebret T.1, Raynaud J.P.2

Charles University - 2nd Faculty of Medicine, Motol Hospital, Dept. of Urology, Prague, Czech Republic

1 Foch Hospital, Dept. of Urology, Suresnes, France, 2University P.M. Curie, Dept. of Biology, Paris, France

Introduction & Objectives: The rise in prostate specific antigen (PSA) is the most sensitive sign of recurrent disease following radical prostatectomy for localized prostate cancer. We aimed to determine weather the dynamic of postoperative PSA decrease measured by ultrasensitive assay could predict biochemical recurrence of the disease.

Introduction & Objectives: There is accumulating evidences that low Testosterone (lowT) levels in prostate cancer patients before treatment are associated with a poor prognosis. Similarly, it has been demonstrated that men with lowT prior medical castration had either earlier tumor recurrences or much higher tumor specific death rates. The aim of the study was to characterize the relationship between the aggressiveness of the tumor assessed by the Gleason score and the preoperative Testosterone serum concentration.

Material & Methods: A total of 201 men treated with radical prostatectomy for localized prostate cancer were followed with ultrasensitive PSA measurements (lower detection limit 0.003 ng/mL) first at two weeks after the operation, then at 1, 2 and 3 months, and subsequently in 3 months‘ intervals. Patients with PSA nadir of 0.2 ng/ mL and more were excluded from the study. Biochemical recurrence was defined as PSA persistently >0.2 ng/mL. The ability of pathologic and clinical parameters to predict relapse was assessed using a Cox proportional hazard regression model. Results: At a mean follow-up of 23 months (range 6-66), biochemical recurrence occurred in 39 of 201 patients (19.4%). In patients with biochemical relapse, the value of PSA nadir was significantly higher (p<0.0001). Relapse rates in men with nadir PSA of less than <0.01 ng/mL (n=106), 0.01-0.04 ng/mL (n=65) and 0.04 ng/ mL or greater (n=30) were 8.5%, 16.9% and 63.3%, respectively. Mean time to PSA nadir was 4.3 months. However, men with biochemical relapse reached the nadir PSA significantly earlier (p<0.007). The PSA nadir correlated significantly with preoperative PSA (r=0.23, p<0.0001). Multivariate analysis showed that the value of PSA nadir was an independent predictor of biochemical recurrence after radical prostatectomy. Conclusions: The nadir serum PSA offers valuable prognostic information and may help to identify men who are at high risk of biochemical recurrence following radical prostatectomy. Another parameters of postoperative PSA dynamic such as time to PSA nadir need to be further studied in order to determine their predictive ability.

Eur Urol Suppl 2009;8(4):294

Material & Methods: 113 consecutive prostate cancer patients, who underwent radical prostatectomy during the year 2007, had a preoperative testosterone determination. Blood samples, drawn between 7 and 10 am, were sent to a central laboratory to assayed Total Testosterone and Bioavailable Testosterone by a validated RIA method. Gleason score was determined in prostate biopsies and RRP specimens by the same uro-pathologist. Patients were stratified in 2 groups according to predominant grade of 3 or 4. Group 1 corresponds to patients with a Gleason score of 6 (3+3) or 7 (3+4) and group 2 corresponds to patients with a Gleason score of 7 (4+3) or 8 (4+4). Results: In the 82 patients allocated to group 1, mean Total Testosterone level was 5.12 ng/mL and in the 31 patients allocated to group 2, mean Total Testosterone level was 3.62 ng/mL. The difference was highly significant (p=0.0004). For Bioavailable Testosterone, in the 82 patients allocated to group1, mean Bioavailable Testosterone level was 1.12 ng/mL and in the 31 patients allocated to group2, mean Bioavailable Testosterone level was 0.8 ng/mL (p=0.043). Thus lowT, also defined as hypogonadism or in the elderly patients as testosterone deficiency, could cause prostate cell deregulation and predisposes the prostate to neoplastic changes. A larger cohort is currently under investigation to consolidate this observation. Conclusions: To detect a potential hypogonadism. the measurement of testosterone levels before any treatment of cancer of the prostate should be added to PSA determination for the prognosis and during the follow up of the treatment.