Late-Stage Presentation of Testicular Cancer Patients Attended a Specialized Hospital: Findings of a Crosssectional Study

Background: Testicular Cancer (TC) is of interest and importance because its incidence has been increasing in most countries over the past four decades. The purpose of this study is to determine the frequency of patients with common histopathology, most common stage during presentation, biochemical and radiological findings, common levels of tumour markers. Methods: This cross-sectional study was carried out in the Department of Medical Oncology of National Institute of Cancer Research and Hospital (NICRH), Mohakhali, Dhaka, Bangladesh from July 2015 to June 2016. A total number of 52 patients were taken as study participants who are admitted as newly diagnosed at the NICRH. Data collection: tumour markers, USG of whole abdomen and chest X-ray were performed to all the patients for determination of the staging of the tumour. Results: The present study found the majority of the patients were found in stage III disease. Patients with Cryptorchidism needed to be educated regarding its early management to reduce the incidence of testicular tumour among them. It was observed that young people could be adequately knowledgeable and optimal awareness could be developed regarding early symptoms of the disease, then they may be found in earlier stage of their disease, which is curable with modern management method. Targeting to alter the cancer patients’ presentation by rising consciousness about TC, prognosis can be largely improved in future. Conclusion: This study was conducted to find out the features which were unknown in perspective of Bangladesh, so that burden of TC can be reduced, and prognosis can be further improved of this potentially curable disease. JOPSOM 2021; 40(1): 26-33

Peritoneal carcinosis in male germ cell tumor patients: a registry study compiled by the German Testicular Cancer Study Group (GTCSG)

Purpose To report on the clinical characteristics, outcome, and frequency of peritoneal carcinosis (PC) in patients with advanced germ cell tumors (GCT), a multicenter registry analysis was carried out. Methods A multicenter registry analysis was conducted by the German Testicular Cancer Study Group (GTCSG) with international collaborators. Data was collected and analyzed retrospectively. Patients were eligible for inclusion if PC was diagnosed either by radiologic or histopathologic finding during the course of disease. Descriptive and explorative statistical analysis was carried out with cancer-specific survival (CSS) as primary study endpoint. Results Collaborators from ten GCT expert centers identified 28 GCT (0.77%) patients with PC after screening approximately 3767 GCT patient files and one case was contributed from a cancer registry request. Patients were diagnosed from 1997 to 2019 at a median age of 37 years (interquartile range, 13). Two patients (7%) presented with stage I and 27 patients (93%) with synchronous metastatic disease at first diagnosis. The primary histology was seminoma in seven (27%) and non-seminoma in 21 patients (72%). PC was detected after a median of 15.3 months from primary diagnosis (range 0–177) and two consecutive treatment lines (range 0–5), respectively. The median CSS from the time of detection of PC was 10.5 months (95%Confidence Interval 0.47–1.30) associated with an overall 2-year CSS rate of 30%. Conclusion PC represents a rare tumor manifestation in GCT patients and was primarily associated with the occurrence of advanced cisplatin-refractory disease conferring to a dismal prognosis.

PNU-74654 Suppresses TNFR1/IKB Alpha/p65 Signaling and Induces Cell Death in Testicular Cancer

Testicular cancer (TC) is a rare malignancy worldwide and is the most common malignancy in males aged 15–44 years. The Wnt/β-catenin signaling pathway mediates numerous essential cellular functions and has potentially important effects on tumorigenesis and cancer progression. The search for drugs to inhibit this pathway has identified a small molecule, PNU-74654, as an inhibitor of the β-catenin/TCF4 interaction. We evaluated the therapeutic role of PNU-74654 in two TC cell lines, NCCIT and NTERA2, by measuring cell viability, cell cycle transition and cell death. Potential pathways were evaluated by protein arrays and Western blots. PNU-74654 decreased cell viability and induced apoptosis of TC cells, with significant increases in the sub G1, Hoechst-stained, Annexin V-PI-positive rates. PNU-74654 treatment of both TC cell lines inhibited the TNFR1/IKB alpha/p65 pathway and the execution phase of apoptosis. Our findings demonstrate that PNU-74654 can induce apoptosis in TC cells through mechanisms involving the execution phase of apoptosis and inhibition of TNFR1/IKB alpha/p65 signaling. Therefore, small molecules such as PNU-74654 may identify potential new treatment strategies for TC.

Can Whole-body MRI Replace CT in Management of Metastatic Testicular Cancer? A Prospective, Non-inferiority Study.

Purpose Concerns of imaging-related radiation in young patients with high survival rates have increased the use of magnetic resonance imaging (MRI) in testicular cancer (TC) stage I. However, computed tomography (CT) is still preferred for metastatic TC. The purpose of this study was to compare whole-body MRI incl. diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) with contrast-enhanced, thoracoabdominal CT in metastatic TC.Methods A prospective, non-inferiority study of 84 consecutive patients (median age 33 years) with newly diagnosed metastatic TC (February 2018 - January 2021). Exclusion criteria were age <18 years, claustrophobia and MRI contraindications. Patients had both MRI and CT before and after treatment. Anonymised images were reviewed by experienced radiologists.Lesion malignancy was evaluated on a Likert scale (1 benign – 4 malignant). Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated on patient and lesion level. For non-inferiority testing, the difference in sensitivity between CT and MRI was calculated. The level of significance was set at 5%. ROC curves and interobserver agreement were calculated.Results On patient level, MRI had 98% sensitivity and 75% specificity compared to CT. On lesion level within each modality, MRI had 99% sensitivity and 78% specificity, whereas CT had 98% sensitivity and 88% specificity. MRI sensitivity was non-inferior to CT (difference 0.57% (95% CI -1.4-2.5%)). The interobserver agreement was substantial between CT and MRI. Conclusion MRI with DWIBS was non-inferior to contrast-enhanced CT in detecting metastatic TC disease. Trial registration www.clinicaltrials.gov NCT03436901, finished July 1st 2021.