Efficacy, tolerability, and safety of teverelix DP in patients with advanced prostate cancer: A multicenter, open-label, phase 2 trial.

BACKGROUND: Teverelix drug product (DP) is a novel injectable gonadotropin-releasing hormone antagonist. METHODS: An adaptive phase 2, open-label, multicenter trial was conducted in patients with advanced prostate cancer to evaluate the efficacy and safety of a combined subcutaneous (SC) and intramuscular (IM) loading dose regimen of teverelix DP of 120 mg SC + 120 mg IM (Group 1; N = 9) or 180 mg SC + 180 mg IM (Group 2; N = 41) administered at a single visit, followed by 6-weekly SC maintenance doses of 120 mg (Group 1) or 180 mg (Group 2), up to Day 168. The primary endpoint was the proportion of patients achieving castration levels with serum testosterone <0.5 ng/mL at Day 28 with a target castration rate of 90%. Injection sites were inspected by the investigator at every visit and reactions (ISRs) were proactively recorded. RESULTS: The target castration rate was reached in Group 2 (97.5%) but not in Group 1 (62.5%). The castration rates were not maintained to Day 42 (Group 2: 82.5%; Group 1: 50.0%). Suppression of testosterone to castrate levels occurred rapidly (median time: 2 days for both groups). Suppression of testosterone, prostate-specific antigen, follicle-stimulating hormone, and luteinizing hormone was sustained throughout the treatment period, being more prominent with the higher dose. The adverse event (AE) profile was similar between groups. The most common AEs were injection-site induration (n = 40: 80.0%), injection-site erythema (n = 35: 70.0%), and hot flush (n = 21: 42.0%). Most ISRs were Grade 1. CONCLUSION: Overall, the teverelix DP doses were generally well-tolerated but did not adequately maintain castration levels.

The Impact of Prostate Cancer Upgrading and Upstaging on Biochemical Recurrence and Cancer-Specific Survival.

Background and Objectives: Significant numbers of prostate cancer (PCa) patients experience tumour upgrading and upstaging between prostate biopsy and radical prostatectomy (RP) specimens. The aim of our study was to investigate the role of grade and stage increase on surgical and oncological outcomes. Materials and Methods: Upgrading and upstaging rates were analysed in 676 treatment-naïve PCa patients who underwent RP with subsequent follow-up. Positive surgical margin (PSM), biochemical recurrence (BCR), metastasis-free survival (MFS), overall (OS) and cancer specific survival (CSS) were analysed according to upgrading and upstaging. Results: Upgrading was observed in 29% and upstaging in 22% of PCa patients. Patients undergoing upgrading or upstaging were 1.5 times more likely to have a PSM on RP pathology. Both upgrading and upstaging were associated with increased risk for BCR: 1.8 and 2.1 times, respectively. Mean time to BCR after RP was 2.1 years in upgraded cases and 2.7 years in patients with no upgrading (p <0.001), while mean time to BCR was 1.9 years in upstaged and 2.8 years in non-upstaged cases (p <0.001). Grade and stage increase after RP were associated with inferior MFS rates and ten-year CSS: 89% vs. 98% for upgrading (p = 0.039) and 87% vs. 98% for upstaging (p = 0.008). Conclusions: Currently used risk stratification models are associated with substantial misdiagnosis. Pathological upgrading and upstaging have been associated with inferior surgical results, substantial higher risk of BCR and inferior rates of important oncological outcomes, which should be considered when counselling PCa patients at the time of diagnosis or after definitive therapy.

Complications after male adjustable suburethral sling implantation.

INTRODUCTION: Argus suburethral sling implantation is a minimally invasive operation with the possibility to adjust the tension of the sling at any time after the procedure, which provides good treatment results for male stress urinary incontinence (SUI). AIM: To determine the predictive factors, the incidence, severity and timing of the onset of complications after Argus sling implantation for males with post-operative SUI. MATERIAL AND METHODS: A total of 41 patients who underwent Argus sling implantation due to post-operative SUI were included. Median follow-up was 12 months. All complications were captured and graded according to severity and classified by timing of onset. Logistic regression analysis was performed to identify predictors of the most common side effects. RESULTS: Overall 22 (54%) of 41 males have experienced 31 complications. Three (7%) patients have experienced only intra-operative, 16 (39%) patients only post-operative and 3 (7%) patients both intra-operative and post-operative complications. The most common intra-operative complications were bladder perforation (12%) and external iliac vein injury (5%), while post-operative complications were acute urinary retention (29%), infection (10%) and perineal pain (7%). Previous radiotherapy has significantly increased the risk of intra-operative complications, while a non-significant tendency was observed for younger age, previous androgen deprivation therapy and grade 3 SUI. In terms of severity, most post-operative complications were classified as grade 3 according to the modified Clavien-Dindo system. CONCLUSIONS: Argus sling implantation provides a tolerable complication rate, where acute urinary retention was the most common side effect. Previous radiotherapy significantly increases the risk of serious intra-operative complications.

Prostate Health Index and Prostate Health Index Density as Diagnostic Tools for Improved Prostate Cancer Detection.

BACKGROUND: To evaluate the diagnostic potential of [-2] proPSA (p2PSA), %p2PSA, Prostate Health Index (phi), and phi density (PHID) as independent biomarkers and in composition of multivariable models in predicting high-grade prostatic intraepithelial neoplasia (HGPIN) and overall and clinically significant prostate cancer (PCa). METHODS: 210 males scheduled for prostate biopsy with total PSA (tPSA) range 2-10 ng/mL and normal digital rectal examination were enrolled in the prospective study. Blood samples to measure tPSA, free PSA (fPSA), and p2PSA were collected immediately before 12-core prostate biopsy. Clinically significant PCa definition was based on Epstein's criteria or ISUP grade ≥ 2 at biopsy. RESULTS: PCa has been diagnosed in 112 (53.3%) patients. Epstein significant and ISUP grade ≥ 2 PCa have been identified in 81 (72.3%) and 40 (35.7%) patients, respectively. Isolated HGPIN at biopsy have been identified in 24 (11.4%) patients. Higher p2PSA and its derivative mean values were associated with PCa. At 90% sensitivity, PHID with cut-off value of 0.54 have demonstrated the highest sensitivity of 35.7% for overall PCa detection, so PHID and phi with cut-off values of 33.2 and 0.63 have demonstrated the specificity of 34.7% and 34.1% for ISUP grade ≥ 2 PCa detection at biopsy, respectively. In univariate ROC analysis, PHID with AUC of 0.77 and 0.80 was the most accurate predictor of overall and Epstein significant PCa, respectively, so phi with AUC of 0.77 was the most accurate predictor of ISUP grade ≥ 2 PCa at biopsy. In multivariate logistic regression analysis, phi improved diagnostic accuracy of multivariable models by 5% in predicting ISUP grade ≥ 2 PCa. CONCLUSIONS: PHID and phi have shown the greatest specificity at 90% sensitivity in predicting overall and clinically significant PCa and would lead to significantly avoid unnecessary biopsies. PHID is the most accurate predictor of overall and Epstein significant PCa, so phi is the most accurate predictor of ISUP grade ≥ 2 PCa. phi significantly improves the diagnostic accuracy of multivariable models in predicting ISUP grade ≥ 2 PCa.

Urinary DNA methylation biomarkers for prediction of prostate cancer upgrading and upstaging.

BACKGROUND: Significant numbers of prostate cancer (PCa) patients experience tumour upstaging and upgrading in surgical specimens that cause serious problems in timely and proper selection of the treatment strategy. This study was aimed at the evaluation of a set of established epigenetic biomarkers as a noninvasive tool for more accurate PCa categorization before radical prostatectomy (RP). METHODS: Quantitative methylation-specific PCR was applied for the methylation analysis of RARB, RASSF1, and GSTP1 in 514 preoperatively collected voided or catheterized urine samples from the single-centre cohort of 1056 treatment-naïve PCa patients who underwent RP. The rates of biopsy upgrading and upstaging were analysed in the whole cohort. RESULTS: Pathological examination of RP specimens revealed Gleason score upgrading in 27.2% and upstaging in 20.3% of the patients with a total misclassification rate of 39.0%. DNA methylation changes in at least one gene were detected in more than 80% of urine samples. Combination of the PSA test with the three-gene methylation analysis in urine was a significant predictor of pathological upstaging and upgrading (P < 0.050), however, with limited increase in overall accuracy. The PSA test or each gene alone was not informative enough. CONCLUSIONS: The urinary DNA methylation assay in combination with serum PSA may predict tumour stage or grade migration post-RP aiding in improved individual risk assessment and appropriate treatment selection. Clinical utility of these biomarkers should be proven in larger multi-centre studies.

Complications and their treatment after midurethral tape implantation using retropubic and transobturator approaches for treatment of female stress urinary incontinence.

INTRODUCTION: Midurethral tape implantation procedures currently are the first-line treatment for female stress urinary incontinence (SUI). AIM: To estimate the most common intraoperative and postoperative complications and their treatment methods after midurethral tape implantation using retropubic (tension-free vaginal tape - TVT) and transobturator (TOT) approaches for the treatment of female SUI. MATERIAL AND METHODS: A retrospective descriptive study was performed on 367 women operated on due to SUI in the period from 2004 to 2015. The SUI diagnosis was confirmed by clinical history and physical examination. According to the surgical technique that was chosen for SUI treatment, all the patients were divided into two groups: the TVT group (n = 112) and the TOT group (n = 255). RESULTS: In total, in 31 (8.45%) of 367 patients complications were observed after midurethral tape implantation. In the TVT group 18 (16.07%) of 112 patients experienced surgery-related complications compared to 13 (5.1%) of 255 patients in the TOT group (p = 0.0005). The most common intraoperative complication in the TVT group was bladder perforation. In the TOT group we had only occasional intraoperative complications. Acute urinary retention was the most common postoperative complication in both groups. It was observed in 13 (11.6%) patients in the TVT group and in 5 (1.96%) patients in the TOT group. CONCLUSIONS: The advantage of midurethral tape implantation using the TOT technique is that it is associated with lower incidence of intraoperative and postoperative complications compared to TVT. The most common complication in our series was acute postoperative urinary retention, which usually required an additional tape loosening procedure.

Malignant mixed epithelial and stromal tumour of the kidney: a case report and a literature review.

INTRODUCTION: Mixed epithelial and stromal tumour of the kidney (MEST) is a rare and distinctive neoplasm accounting for 0.2% of all renal cancers. Most of these tumours behave in a benign fashion but 13 cases with malignant transformation have already been reported. We present the first case of an extremely aggressive MEST with rapid recurrence after radical treatment, demonstrating objective response to chemotherapy. CASE PRESENTATION: A 31-year-old female presented to the hospital complaining of gross hematuria. Computed tomography (CT) revealed an intraparenchymal mass in the left kidney forming a tumour thrombus in the inferior vena cava (IVC). Metastatic disease was ruled out and, under the clinical diagnosis of renal cell carcinoma, left radical nephrectomy with IVC thrombectomy was performed. The histopathological examination confirmed malignant MEST of the kidney. At the follow-up 12 months after surgery, a recurrent tumour in the left paravertebral area and a tumour thrombus in the IVC were detected. A second surgery was recommended and the mass from the paravertebral area was removed, so resection of the IVC with prosthetic replacement was performed. The histopathologic examination confirmed a recurrent malignant MEST. At the follow-up three months after the second surgery disease progression was diagnosed, so chemotherapy with ifosfamide and doxorubicin was initiated. The CT scan performed 14 months after the chemotherapy confirmed a stable process of the disease with no signs of progression. CONCLUSIONS: A literature review and our case report confirm the existence of extremely aggressive malignant MEST that shows response to chemotherapy. However, more reports are needed to improve our understanding about the biology of the MEST to develop any recommendations on personalized therapy.

Treatment of recurrent stress urinary incontinence in women: comparison of treatment results for different surgical techniques.

INTRODUCTION: There is still no consensus on which surgical technique is the most effective for female recurrent stress urinary incontinence after the initial surgery. AIM: To compare the long-term treatment outcomes of Burch colposuspension operation, transobturator tape implantation (TOT) and tension-free vaginal tape (TVT) procedures performed for female recurrent stress urinary incontinence after the initial surgery. MATERIAL AND METHODS: A retrospective study was performed on 45 women operated on for recurrent stress urinary incontinence after the initial surgery. Depending on the surgical approach, the patients were divided into three groups: group I (n = 19) - Burch colposuspension operation, group II (n = 16) - TOT, and group III (n = 10) - TVT operation was performed. The treatment results were assessed using the UDI-6 (Urogenital Distress Inventory) and IIQ-7 (Incontinence Impact Questionnaire) short form questionnaires. We included one additional question: Is the patient satisfied with the treatment outcome? We classified the urinary continence results after surgery as good when patients were cured or improved, and as bad when the treatment failed. RESULTS: Good urinary continence results were observed in 84.2% of patients in group I, 93.8% of patients in group II, and 90% of patients in group III. 68.4% of patients in group I, 81.3% of patients in group II, and 90% of patients in group III were satisfied with the treatment outcomes. CONCLUSIONS: Burch colposuspension operation, TOT and TVT procedures performed for the female recurrent stress urinary incontinence treatment are effective and show similar good urinary continence results and similar number of patients satisfied with the treatment outcomes.