[CAPRA score vs minimal residual disease as predictors of biochemical recurrence after radical prostatectomy.] / La puntuación CAPRA frente a los subtipos de enfermedad residual mínima para predecir la recidiva bioquímica después de la prostatectomía radical.

OBJECTIVE: To compare the classification CAPRA (based on clinical-pathological findings) and minimal residual disease (MRD) (based on biological characteristics) to predict biochemical failure (BF). METHOD AND PATIENTS: The clinical-pathological findings of the prostate biopsy were used to determine the CAPRA score, classifying patients into low, intermediate and high risk. Blood and bone marrow samples to detect circulating prostate cells (CPCs) and micro-metastasis were taken. The samples were classified as positive if ≥1 prostate cell was detected, forming three subgroups; Group A (MRD negative), Group B (micro-metastasis positive, CPC negative) and Group C (CPC positive). Patients were followed-up for 10 yearsor BF. Kaplan-Meier biochemical failure free survival (BFFS) curves, a predictive flexible parameter survival model and mean restricted survival times (MRST) were determined. RESULTS: 347 men participated, BF risk increased with increasing CAPRA score, HR 1.21 intermediate, 1.64 high risk; versus MRD HR 1.91 and 4.43 for Groups Band C. After 10 years the BFFS and MRST were 76%, 50% and 17% and 9, 7 and 5 years respectively for CAPRA versus 94%, 57% and 26% and 10, 9 and 6 years respectively for MRD. The concordance between observed and predicted BFFS was acceptable for CAPRA (Harrell´s C 0.64) and very good (0.92) for MRD. The BFFS curves for MRD were not proportional with time, they were similar for 5 years for Groups A and B, with increasing BFFS in Group B there after.The CAPRA score did not distinguish between Groups A and B, one third of low risk CAPRA patients had CPCs detected. CONCLUSIONS: The MRD classification was superior to CAPRA, differentiating between early and late failure.

OBJETIVO: Comparar la puntuación CAPRA (en función de los hallazgos clínico-patológicos) y la enfermedad residual mínima (ERM) (en función de las propiedades biológicas) para predecir la recidiva bioquímica (RB).MÉTODOS Y PACIENTES: Los hallazgos clínico-patológicos de biopsias de próstata determinaron la puntuación CAPRA definiendo pacientes de bajo, intermedio y alto riesgo de la RB. Se obtuvieron muestras de sangre y médula ósea para detectar CPCs (Células Prostáticas Circulantes) y micro-metástasis usando inmunocitoquímica. Se clasificaron como positivas si se detectaba ≥1 célula en la muestra. Se formaron tres subgrupos: Grupo A (ERM negativo), Grupo B (micro-metástasis positivo, CPC negativo) y Grupo C (CPC positivo). Los pacientes fueron seguidos durante diez años o hasta la RB. Las curvas de supervivencia libre de recidiva bioquímica (SLRB) se construyeron usando el método de Kaplan Meier, un modelo de parámetro flexible (supervivencia predecida) y el tiempo de supervivencia medio restringido (TSMR) para cada subgrupo. RESULTADOS: 347 hombres participaron; el riesgode RB aumentó proporcionalmente; HR 1,21 riesgo intermedio,1,64 riesgo alto para CAPRA versus 1,91 Grupo B y 4,43 Grupo C para EMR. Después de diez años, el SLRB y el TSMR fueron 76%, 50%, 17% y 9,7 y 5 años respectivamente para CAPRA versus 94%, 57%, 26% y 10, 9 y 6 años respectivamente para EMR. El acuerdo entre SLRB observada y prevista fue aceptable para CAPRA (Harrell´s C 0,64) y muy buena (0,92) para EMR. Las curvas SLRB para la EMR no fueron proporcionales; para Grupos A y B fueron similares hasta cinco años, luego hubo una falla creciente en el Grupo B. La puntuación de CAPRA no logró distinguir entre los Grupos A y B, un tercio del Grupo C de alto riesgo tenía una puntuación CAPRA de bajo riesgo. CONCLUSIONES: La clasificación ERM fue superior de la CAPRA, diferenciando entre la RB temprana y tardía.

Detection and characteristics of primary circulating prostate cells; association with micrometastasis and implications for surgical treatment of men with prostate cancer.

OBJECTIVES: To determine the frequency of primary circulating prostate cells in men with prostate cancer at the time of diagnosis, the association with micrometastasis, sub-classification for CD82 and the relation with pathological stage. To determine their clinical usefulness to identify patients in whom radical prostatectomy would be first choice therapy. METHODS: Men with the diagnosis of prostate cancer before definitive therapy. Blood and bone marrow samples were taken, mononuclear cells separated by differential centrifugation and prostate cells identified with immunocytochemistry using anti-PSA. Positive samples were sub-classified with anti-CD82. Details of serum PSA, Gleason score and pathological stage were registered. RESULTS: Of 77 men 58 (75.3%) had primary CPCs detected, there was an association with stage but not Gleason. 31 (40.3%) had micrometastasis with an association with stage and Gleason score. CPC-negative patients had fewer micrometastasis detected, 1/19 versus 30/58 (p<0.003). There was an inverse relation between CD82 expression and Gleason score, men with CPCs expressing CD82 had fewer micrometastasis. The combined group of CPC negative and CPC positive CD82 positive men showed a sensitivity of 87%and specificity of 73.9% for the absence of micrometastasis. CONCLUSIONS: The detection of CPCs and sub-classification with CD82 could be clinically useful to identify men with a significantly lower risk of micrometastais and as a consequence to identify men in whom radical prostatectomy could be the best initial treatment.

P504S expressing circulating prostate cells as a marker for prostate cancer.

Prostate cancer is the most commonly diagnosed cancer in men and the second leading cause of cancer deaths. The serum prostate specific antigen (PSA) is the only biomarker routinely used in screening. The aim of this study was to develop a system to test the presence of circulating prostate cells in men without a diagnosis of prostate cancer in relation with age, serum PSA levels and prostate biopsy by determining the co-expression of several markers such as CD82, HER-2 and matrix metalloproteinase 2 (MMP-2). For this purpose mononuclear cells were separated from blood using differential centrifugation and then prostate cells were identified by using standard immunocytochemical method. Results indicated that among 409 men screened for prostate cancer 16.6% were positive for circulating prostate cells. Cells were positive for MMP-2 and HER-2 in 100 and 14.3% of cases, respectively, without an association with age or PSA levels. However, CD82 protein expression was associated with older age and low grade tumors. It can be concluded that the study of circulating prostate cells with various markers could be a useful complementary screening test for prostate cancer in men with increased PSA level.