Evaluation of miR-148a-3p and miR-106a-5p as Biomarkers for Prostate Cancer: Pilot Study.

MicroRNAs (miRNAs) are a class of small non-coding RNAs that may function as tumor suppressors or oncogenes. Alteration of their expression levels has been linked to a range of human malignancies, including cancer. The objective of this investigation is to assess the relative expression levels of certain miRNAs to distinguish between prostate cancer (PCa) from benign prostatic hyperplasia (BPH). Blood plasma was collected from 66 patients diagnosed with BPH and 58 patients with PCa. Real-time PCR technology was used to evaluate the relative expression among the two groups for miR-106a-5p and miR-148a-3p. The significant downregulation of both miRNAs in plasma from PCa versus BPH patients suggests their potential utility as diagnostic biomarkers for distinguishing between these conditions. The concurrent utilization of these two miRNAs slightly enhanced the sensitivity for discrimination among the two analyzed groups, as shown in ROC curve analysis. Further validation of these miRNAs in larger patient cohorts and across different stages of PCa may strengthen their candidacy as clinically relevant biomarkers for diagnosis and prognosis.

Post-Pandemic Aftermath: A Two-Year Follow-Up of the Effect of COVID-19 on Oncological Outcomes after Radical Prostatectomy for Prostate Cancer.

PURPOSE: This study aimed to evaluate the indirect effect of the Coronavirus Disease 2019 (COVID-19) pandemic on the surgical outcomes and oncological results of patients who underwent surgery during the lockdown period. METHODS: We analysed data from 423 patients who underwent radical prostatectomy between 2016 and 2022, with a cut-off date of March 16, 2020. Patients were categorised into two groups, namely, pre-lockdown (n = 289) and during lockdown (n = 134). Perioperative variables, histopathological findings and oncological outcomes, including prostate-specific antigen (PSA) levels and biochemical recurrence (BCR), were assessed. RESULTS: The number of radical prostatectomy increased by 24.26% during lockdown. The study included patients with a mean follow-up of 21 months. A nonsignificant trend towards a higher PSA level at presentation was found (14.22 vs. 12.53 ng/dL, p = 0.216). The International Society of Urological Pathology grade was not significantly different among radical prostatectomy specimens (p = 0.669). Lymph node involvement increased during the COVID-19 period (p = 0.046). The pT classification in prostatectomy specimens increased during the pandemic, but the difference from the pre-pandemic value was not statistically significant. The BCR rates were 24.6% pre-lockdown and 29.9% during lockdown (p = 0.136). CONCLUSIONS: The COVID-19 pandemic led to poor postoperative results. Through a 2-year follow-up, this research investigated the effect of the pandemic on the oncological outcomes, particularly BCR, of patients who underwent radical prostatectomy. Further extended investigations and multi-institutional studies should be conducted to quantify the effect of the pandemic on various cancer outcomes and inform crisis management strategies.

Comprehensive Analysis of Perioperative Factors Influencing the Risk of Biochemical Recurrence in Patients with Radical Prostatectomy.

PURPOSE: To analyze the perioperative factors that influence the risk of biochemical recurrence (BCR) in patients with localized PCa undergoing radical prostatectomy Materials and Methods: A total of 457 patients, operated by 2 surgeons in our high-volume oncological center were included in the initial database. Patients who underwent RP for clinically localized PCa in our clinic from 2016 to 2021 were included in the study. Perioperative data were retrospectively reviewed for this study. Follow-up data including post-operative PSA and adjuvant treatment was prospectively gathered by contacting the patients or from the follow-up consultation. Final database was composed of 366 patients who underwent open or 3D laparoscopic RP. Statistical analysis was performed to emphasize the most powerful parameters that influence the BCR.  Results: Accounting for multivariable analysis, 4 parameters were statistically significant: initial PSA (iPSA), Gleason score, vascular involvement and positive surgical margins. For the group of patients with no positive margins, 3 parameters were statistically significant: iPSA above 10,98 ng/mL (AUC=0,71); lymph node involvement and Gleason score. Multivariable Cox regression showed that positive margins and iPSA had a significant impact on the time to BCR. Patients that received adjuvant therapy were excluded from the study. Out of the whole cohort, 27,3% of patients presented BCR. CONCLUSION: Perioperative factors need to be carefully analyzed and a detailed follow-up needs to be conducted in order to assess the risk of biochemical recurrence, resulting in the optimal time for adjuvant treatment implementation.

3D Laparoscopic Ureterolysis for Retroperitoneal Fibrosis Secondary to Radical Hysterectomy and Radiation Treatment for Cervical Cancer: Results from the Oncological Institute, Cluj Napoca.

BACKGROUND: Ureterolysis represents the surgical treatment for retroperitoneal fibrosis. The aim of the study was to review the outcomes of patients who had undergone radical hysterectomy and radiotherapy for cervical cancer that later developed retroperitoneal fibrosis, for whom 3D laparoscopic ureterolysis was performed in our department and to review current published studies. METHODS: We present a series of cases consisting of 6 patients with secondary retroperitoneal fibrosis. In all cases, the intervention was performed by the same surgeon from the Oncological Institute "Prof. Dr. Ion Chiricuța" Cluj-Napoca, Romania. We carried out a literature review, searching in the PubMed and MEDLINE studies published between 2000 and 2021 relevant to the matter and a total of 12 papers were selected. We reviewed the functional outcomes of patients that underwent minimally invasive ureterolysis. RESULTS: 3D laparoscopic ureterolysis was performed in 6 patients. Mean operative time was 166 minutes and mean blood loss was 203 mL. No surgery required conversion. Five patients showed good functional results after ureteral stent removal. In one case, the patient developed acute pyelonephritis and the ureteral stents were kept. CONCLUSIONS: Laparoscopic ureterolysis for retroperitoneal fibrosis secondary to operated and radiation-treated cervical cancer represents one of the most complex and challenging surgeries in the urological field. From personal experience we conclude that in oncological centers with vast experience in laparoscopy this minimally invasive approach is feasible and safe. Published data, even though scarce, strengthens our results and the need for this surgery in patients with retroperitoneal fibrosis with urological impact. The laparoscopic approach comes with good functional results and with the advantages of faster post-operative recovery comparing to open surgery and comparable results with the precision and dexterity offered by the robotic approach, but with lower economic burden.

TP53 gene implications in prostate cancer evolution: potential role in tumor classification.

Background and aims: Prostate adenocarcinoma (PRAD) is a complex disease that can be driven by alterations in both coding and noncoding genes. Recent research has identified coding and non-coding genes that are considered to play important roles in prostate cancer evolution and which may be used as biomarkers for disease diagnosis, prognosis, and treatment. TP53 is a critical hub gene in prostate cancer. Advanced studies have demonstrated the crosstalk between coding and non-coding RNAs, particularly microRNAs (miRNAs). Methods: In this study, we investigated the roundabout of TP53 and their regulatory miRNAs (miR-15a-5p, miR-34a-5p, and miR-141-3p) based on the TCGA data set. We validated an additional patient cohort of 28 matched samples of patients with PRAD at tissue and plasma level. Results: Therefore, using the UALCAN online database, we evaluated the expression level in PRAD of these genes revealing overexpression of TP53. qRT-PCR validation step endorsed the expression level for these genes. Additionally, we evaluated the expression level of the four key miRNAs (miR-15a-5p, miR-34a-5p, and miR-141-3p) interconnected as a network at tissue and plasma levels. Conclusions: Through these results, we demonstrated the essential function of TP53 and its associated miRNAs that play a significant role in tumor control, highlighting miRNAs' potential as future therapeutic targets and biomarkers with important implications in managing prostate cancer.

MicroRNA Dysregulation in Prostate Cancer.

Prostate cancer biology is complex, and needs to be deciphered. The latest evidence reveals the significant role of non-coding RNAs, particularly microRNAs (miRNAs), as key regulatory factors in cancer. Therefore, the identification of altered miRNA patterns involved in prostate cancer will allow them to be used for development of novel diagnostic and prognostic biomarkers. PATIENTS AND METHODS: We performed a miRNAs transcriptomic analysis, using microarray (10 matched pairs tumor tissue versus normal adjacent tissue, selected based on inclusion criteria), followed by overlapping with TCGA data. A total of 292 miRNAs were differentially expressed, with 125 upregulated and 167 downregulated in TCGA patients' cohort with PRAD (prostate adenocarcinoma), respectively for the microarray experiments; 16 upregulated and 44 downregulated miRNAs were found in our cohort. To confirm our results obtained for tumor tissue, we performed validation with qRT-PCR at the tissue and plasma level of two selected transcripts, and finally, we focused on the identification of altered miRNAs involved in key biological processes. RESULTS: A common signature identified a panel of 12 upregulated and 1 downregulated miRNA, targeting and interconnected in a network with the TP53, AGO2, BIRC5 gene and EGFR as a core element. Among this signature, the overexpressed transcripts (miR-20b-5p, miR-96-5p, miR-183-5p) and the downregulated miR-542-5p were validated by qRT-PCR in an additional patients' cohort of 34 matched tumor and normal adjacent paired samples. Further, we performed the validation of the expression level for miR-20b-5p, miR-96-5p, miR-183-5p plasma, on the same patients' cohort versus a healthy control group, confirming the overexpression of these transcripts in the PRAD group, demonstrating the liquid biopsy as a potential investigational tool in prostate cancer. CONCLUSION: In this pilot study, we provide evidence on miRNA dysregulation and its association with key functional components of the PRAD landscape, where an important role is acted by miR-20b-5p, miR-542-5p, or the oncogenic cluster miR-183-96-182.

3D laparoscopic salvage radical prostatectomy: mini-series report and review of the literature.

PURPOSE: Salvage therapy represents a rescue therapy, given after the first line of treatment had failed.The purpose of this study was to review the outcomes of patients who underwent salvage laparoscopic radical prostatectomy (sLRP) in our department and to review current published studies. METHODS: Our mini-series consisted of 6 patients with recurrent prostate cancer(PCa) after non-surgical primary treatment. All interventions were performed by a single surgeon from the Oncological Institute "Prof. Dr. Ion Chiricuta" Cluj Napoca, Romania.A literature review was carried out in June 2020 using the PubMed and MEDLINE databases to identify relevant studies published in the literature between 2000 and 2020. Six papers were selected for our review.We reviewed the oncological and functional outcomes of patients that underwent sLRP. RESULTS: Extraperitoneal sLRP was performed in 6 patients. Biochemical failure after primary treatment developed between one and five years. Mean operative time was 135.5 min, mean blood loss was 328 ml. No intraoperative complications occurred and no conversions to open surgery. R0 was achieved in 5 out of the 6 patients (83.5%). Out of the 6 patients 2 are incontinent. CONCLUSIONS: SLRP remains an underused procedure and a missed therapeutic opportunity for selected patients. From published data and personal experience, we conclude that in experienced hands sLRP for localized prostate cancer is a feasible, safe and efficient method to treat recurrent PCa. Short-term oncological outcomes are optimistic but further studies need to be made to observe the long-term outcomes.

PSA Based Biomarkers, Imagistic Techniques and Combined Tests for a Better Diagnostic of Localized Prostate Cancer.

Prostate cancer represents the most encountered urinary malignancy in males over 50 years old, and the second most diagnosed after lung cancer globally. Digital rectal examination and prostatic specific antigen were the long-time standard tools for diagnosis but with a significant risk of overdiagnosis and overtreatment. Magnetic resonance imaging recently entered the diagnosis process, but to this date, there is no specific biomarker that accurately indicates whether to proceed with the prostate biopsy. Research in this area has gone towards this direction, and recently, serum, urine, imagistic, tissue biomarkers, and Risk Calculators promise to help better diagnose and stratify prostate cancer. In order to eliminate the comorbidities that appear along with the diagnosis and treatment of this disease, there is a constant need to implement new diagnostic strategies. Important uro-oncology associations recommend the use of novel biomarkers in the grey area of prostate cancer, to better distinguish the next step in the diagnostic process. Although it is not that simple, they should be integrated according to the clinical policies, and it should be considered that statistical significance does not always equal clinical significance. In this review, we analyzed the contribution of prostate-specific antigen (PSA)-based biomarkers (PHI, PHID, 4Kscore, STHLM3), imagistic techniques (mp-MRI and mp-US), and combined tests in the early diagnosis process of localized prostate cancer.