Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study.

BACKGROUND: Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA). METHODS: This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4 mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (ß-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded. RESULTS: Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with ß-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression. CONCLUSION: In patients with PCa and bone metastases treated with ZA, ß-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially important.

Real-time quantification of human telomerase reverse transcriptase mRNA in the plasma of patients with prostate cancer.

The aim of this study was to evaluate the potential diagnostic value of quantitative analysis of human telomerase reverse transcriptase (hTERT) mRNA in plasma for noninvasive diagnosis of prostate cancer (PCa). Expression levels of hTERT were analyzed by real-time quantitative RT-PCR in 68 patients showing elevated prostate-specific antigen (PSA) levels and a control group of 44 healthy volunteers. Sensitivity and specificity were determined and compared to the corresponding PSA values. Median values for hTERT gene expression in the PCa patients (0.72 ng; range 0.01-12.86) were statistically significantly higher (P < 0.001) than in the control group (0.13 ng; 0.02-0.35). Patients with clinically confirmed prostatitis showed lower plasma hTERT expression than PCa patients (0.29; 0.01-66.07). At a cutoff value of 0.35 sensitivity and specificity for the diagnosis of PCa were 81% and 60%, respectively. We suggest that hTERT mRNA in plasma is a very specific and sensitive method that may aid to differentiate between malignant and nonmalignant prostate tissue and may be a useful marker (in combination with PSA) for early PCa diagnosis.

[Prognostic factors in tumors of the upper urinary tract]. / Factores pronósticos de los tumores del tracto urinario superior.

Review of patients treated for tumours of the upper urinary tract (UUTT) in our hospital during the 1969-1992 period. The characteristics studied were: stage (TNM 1987), grade (OMS), associated vesical tumour, location of primitive tumour, size, number, surgery performed and presence of tumoral relapse. Cox's regression model was used for the analysis of prognostic factors with survival time as the response variable. The sample has 92 patients (78% men and 22% women), average age 64 years. The tumours were: 46 pyelitic, 36 ureteral and 10 mixed. Stage distribution was: 13 pTa (14%), 41 pT1 (45%), 16 pT2 (17%), 15 pT3 (17%), 3 pT4 (7%); grade distribution: 22 grade I (24%), 54 grade II (59%) and 16 grade III (17%) 48% cases presented associated vesical tumour and 15% relapsed. The sample's median survival was 81 months and survival probability at 5 and 10 years was 52% and 45%. A significant association with survival time was shown by: stage, grade, sex and renal annulment. The multivariant analysis selected: 1) stage; 2) renal annulment and 3) sex. The predictive power of staging is indisputable, thus becoming the first selected variable. Renal annulment and sex factors add independent information on evolution. The information provided by the tumour's grade highly correlates to that of the stage, and therefore it was not selected in the multivariant analysis.