Abstract
The aim of the study was to evaluate prognosis for biochemical recurrence (BR) by analysing the pathological and biological characteristics of prostate cancer (PCa) after radical prostatectomy (RP). There were 130 men with clinically localized PCa in whom pretreatment serum PSA level and Ki-67, prostate specific membrane antigen (PSMA), glucose transporter-1 (GLUT-1), vascular endothelial growth factor (VEGF), microvessel density (MVD) and human telomerase reverse transcriptase (hTERT) proteins expression, based on number of immunohistochemically positive cells (labelling index), were retrospectively studied. In order to assess the prognostic significance of analysed variables in univariate and multivariate Cox analysis, patients were dichotomized based on cut-off points chosen by receiver operating characteristic (ROC) curves. There were 83 males (63.8%) at pT stage 1–2 and 47 (36.1%) at pT stage 3–4, respectively, with median (range) age of 62.8 years (49–77), and median follow-up of 78.5 months (12–148). In 42 (32.3%) men BR was found. In univariate analysis, tumour biological features: PSA ≤ 8 ng/mL (p = 0.006), Ki-67LI ≤ 12.7% (p = 0.015), VEGFLI>11.0% (p = 0.030), and hTERTLI>6.7% (p = 0.016), but not clinicopathological parameters, appeared to be positive prognosticators for BRFS. In the Cox analysis, Ki-67 lost its significance, and clinicopathological parameters appeared to be nonsignificant. The independent negative prognostic factors for BRFS were: PSA > 8.0 ng/mL, (Hazard ratio = 2.75, p = 0.003), GLUT-1 > 19.1% (HR = 2.1, p = 0.032), VEGF≤11.0% (HR = 1, p = 0.024) and hTERT≤6.7% (HR = 1, p = 0.017). High PSA level, and GLUT-1 expression and lower VEGF and nuclear hTERT expression may indicate the great role of hypoxia in BR induction in PCa.
Highlights
Prostate cancer (PCa), the most common malignancy in males, is characterized by intratumoral heterogeneity and a Prostate-specific antigen (PSA) has been generally used for screening of PCa, post diagnostic PSA surveillance or monitoring following treatment
We showed that increase of pathological tumour volume and tumour grade was associated with statistically significant increase in serum PSA, Ki-67 [14] and prostate specific membrane antigen (PSMA) expression [15], for telomerase enzyme activity the relation was opposite, indicating extranuclear telomere activity independent of telomere lengthening, and suggesting that it cannot be considered as a marker of malignancy [15]
We have shown that none of the analyzed clinical and pathological features of PCa was shown to have a greater impact on patients’ biochemical recurrence-free survival (BRFS) than tumour biological features, which is in agreement with recently published studies showing greater significance of biomarkers than clinic-pathological features in risk assessment for biochemical recurrence (BR) after radical prostatectomy (RP) [6, 11, 18]
Summary
Prostate cancer (PCa), the most common malignancy in males, is characterized by intratumoral heterogeneity and a Prostate-specific antigen (PSA) has been generally used for screening of PCa, post diagnostic PSA surveillance or monitoring following treatment. Qualification to treatment of individual patient is imprecise and 30–50% of patients have biochemical relapse within 10-years after RP or image-guided radiotherapy [5, 6], which would never progress to clinical metastasis. It is considered, that PSA has limited diagnostic and prognostic value and a low specificity and sensitivity resulting in frequent misdiagnosis [3]. The test has potential harms for prostate cancer screening and patients’ follow-up (overdiagnosis - false positive, complications of unnecessary biopsy) or overtreatment (surgery, radiation treatment) [3, 4]
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