Early prediction of prostate cancer biochemical recurrence and identification of disease persistence using PSA isoforms and human kallikrein-2.

BACKGROUND: The role of isoforms of prostate specific antigen (PSA) and other kallikrein-related markers in early detection of biochemical recurrence (BCR) after radical prostatectomy (RP) is not well known and serum PSA is currently used in preoperative risk nomograms. OBJECTIVE: The aim of this research was to study pre- and early postoperative levels of important PSA isoforms and human kallikrein-2 to determine their ability to predict BCR and identify disease persistence (DP). METHODS: This study included 128 consecutive patients who underwent RP for clinically localized prostate cancer. PSA, fPSA, %fPSA, [-2]proPSA, PHI and hK2 were measured preoperatively, at 1 and 3 months after RP. We determined the ability of these markers to predict BCR and identify DP. RESULTS: The DP and BCR rate were 11.7%and 20.3%respectively and the median follow up was 64 months (range 3-76 months). Preoperatively, the independent predictors of BCR were PSA (p-value 0.029), [-2]proPSA (p-value 0.002) and PHI (p-value 0.0003). Post-RP, PSA was the single marker correlating with BCR, both at one (p-value 0.0047) and 3 months (p-value 0.0004). PSA, fPSA, [-2]proPSA and PHI significantly correlated to DP at 1 and 3 months post-RP (p-value <  0.05), although PSA had the most significant existing correlation (p-value <  0.0001). CONCLUSIONS: [-2]proPSA and PHI are preoperative predictors of BCR and DP that outperform the currently used serum PSA. At the early postoperative period there is no additional benefit of the other markers tested.

Morbidity and mortality after open radical cystectomy and ileal diversion - 10 years experience and a comprehensive assessment in a single tertiary center.

Open radical cystectomy (ORC) remains the gold standard for the treatment of muscle-invasive and high-risk non-muscle invasive bladder cancer unsuitable for bladder preservation techniques. Despite improvements in operative technique and perioperative care, it continues to be associated with significant complications. We analyzed our series of prospectively collected data of patients who underwent ORC at a tertiary referral academic center and evaluated early and late postoperative complications and mortality. The records of 391 ORCs with ileal diversion performed at our institution between January 2008 and July 2018 for non-metastatic transitional bladder carcinoma and other distinct pathological types were analyzed. Perioperative mortality was determined and 30-day and 90-day complications were reported according to the Martin Criteria and the European Association of Urology and graded according to the five-grade Clavien-Dindo classification. Univariate and multivariate analyses were used to evaluate predictors of complications and mortality. Gastrointestinal and infectious complications represented 41% and 43% of the total complications observed at 30 and 90 days after the surgery, respectively. The strongest predictor of infectious complications was the choice of ileal neobladder as the urinary diversion (p≤0.0001). Diabetes was a predictor of the overall, major and major infectious complications (p<0.05). The 30-day mortality rate was 1% while the 90-day mortality rate was 1.5%. Age ≥75 was the single predictor of mortality at both 30-days (p-value 0.003) and 90-days (p-value 0.01) in univariate and multivariate analyses. ORC is a morbid procedure, associated with a high mortality rate. Elderly patients should have proper counseling before the indication of this procedure. Gastrointestinal and infectious complications represent the most common and serious complications, and the study of their predictors is of the utmost importance.

Is Engrailed-2 (EN2) a truly promising biomarker in prostate cancer detection?

Purpose: Prostate-specific antigen (PSA) is a sensitive but unspecific marker for prostate cancer (PC) detection, which may result in harms including overdiagnosis and overtreatment. Therefore, the development of new markers is of absolute value. The urinary level of engrailed-2 (EN2) protein has been recently suggested as a promising PC biomarker, correlating with tumour volume and stage. This study evaluated EN2 and its potential use in clinical practice.Materials and methods: Urinary EN2 was assessed by different commercially available enzyme-linked immunosorbent assay kits. The study sample included 90 patients with clinically localized PC compared to 30 healthy controls, and a group of 40 patients indicated for prostate biopsy due to an elevated PSA level where both pre- and post-digital rectal examination urine samples were collected.Results: No statistical difference between the patient group and the control group was obtained in all measured variables. There was no significant correlation between urinary EN2 and serum PSA, tumour staging and grading. Attentive DRE did not lead to significant changes of urinary EN2 or impact on its predictive power.Conclusions: Our results show that EN2 as a PC biomarker brings no additional value to the current use of PSA in clinical practice.

Differences in Urinary Amino Acid Patterns in Individuals with Different Types of Urological Tumor Urinary Amino Acid Patterns as Markers of Urological Tumors.

BACKGROUND: Insufficient specificity and invasiveness of currently used diagnostic methods raises the need for new markers of urological tumors. The aim of this study was to find a link between the urinary excretion of amino acids and the presence of urological tumors. MATERIALS AND METHODS: Using ion-exchange chromatography, we tested urine samples of patients with prostate cancer (n=30), urinary bladder cancer (n=28), renal cell carcinoma (n=16) and healthy volunteers (control group; n=21). RESULTS: In each category, we found a group of amino acids which differed in concentration compared to the control group. These differences were most significant in sarcosine in patients with prostate cancer; leucine, phenylalanine and arginine in those with bladder cancer; and sarcosine, glutamic acid, glycine, tyrosine and arginine in the those with renal cell carcinoma. CONCLUSION: Results of our research imply a possible connection between the occurrence of specific types of amino acids in the urine and the presence of urological tumors.

Stratification model based on early postprostatectomy prostate-specific antigen kinetics may help to reduce the risk of overtreatment in candidates for adjuvant radiotherapy.

OBJECTIVE: The aim of this study was to construct a stratification model based on early postoperative kinetics of prostate-specific antigen (PSA) to select the most suitable high-risk patients for early intervention after radical prostatectomy (RP). MATERIALS AND METHODS: The study evaluated 205 men who had undergone RP without any adjuvant treatment. All of the patients had positive surgical margins, extracapsular extension and/or seminal vesicle invasion. The patients underwent multiple ultrasensitive PSA measurements on days 14, 30, 60 and 90 after RP, and subsequently at 3 month intervals. The ability of particular PSA measurements to predict biochemical recurrence (BCR) was assessed using the area under the curve (AUC). A sequential mathematical decision procedure was constructed to create a stratification model. RESULTS: During the median follow-up of 45.9 months, 106 patients (51%) experienced BCR. Prediction of BCR in terms of the AUC for PSA measurements on days 14, 30, 60 and 90 after the surgery was 0.61, 0.70, 0.80 and 0.82, respectively. In the multivariate analysis, only PSA after RP remained as a predictor of progression-free survival (p < 0.001). The stratification model based on calculated cut-off values for PSA on day 30 (0.068 ng/ml) and PSA on day 60 (0.015 ng/ml) reduced the potential overtreatment rate by 37%. CONCLUSIONS: The results imply that ultrasensitive PSA values obtained very early after RP correlate with the presence of recurrent disease in high-risk patients. Incorporating these readily available variables into risk stratification models may help to individualize the administration of adjuvant radiotherapy and thus to minimize overtreatment.