Testicular Cancer Commons

MicroRNAs (miRNAs) are emerging as circulating biomarkers in germ cell tumors (GCT) with potential to guide management. Their role and expression patterns are more established in testicular GCTs, while lesser data exist in ovarian GCTs (OGCT). Patients diagnosed with OGCT with plasma and tumor tissue available in our provincial biobank were included. Total RNA was extracted, and RT-qPCR was performed to measure miR-371-3 and miR-302/367 levels. Healthy plasma and ovarian tissue served as controls. Statistical analyses were performed using ANOVA and the Mann-Whitney U test. Clinicopathologic data was collected by chart review. From 2007 to 2022, 23 patients with OGCT were identified: 13 with viable non-teratoma germ cell (VNTGC) and 10 with immature teratoma germ cell (ITGC) tumors. Compared to healthy controls, all patients with VNTGC but not ITGC tumors had significantly higher miRNA levels in preoperative plasma and tumor tissue. Plasma miRNA kinetics correlated with disease burden, decreasing to undetectable levels following treatment, and increasing significantly upon relapse. MiR-371-3 and miR-302/367 are highly expressed in ovarian VNTGC but not ITGC tumors, and their plasma levels correlate with disease burden. Future studies validating these findings in a larger cohort are needed to develop miRNAs as circulating biomarkers for clinical use.

647 Background: The primary treatment of most mNSTC is chemotherapy followed by surgery if the residual disease (RD) is >1 cm. However, conventional imaging lacks the specificity to characterize the tissue, often leading to overtreatment. This study hypothesizes that integrating CT-driven radiomics features with plasma miR371 and miR375 will enhance the predictive accuracy of Machine Learning (ML) models to predict teratoma, viable germ cell (vGCT) and fibrosis/necrosis (F/N) in mNSTC patients with RD. Methods: 111 lesions from52 patients, including residual teratoma (n=57), F/N (n=33), vGCT (n=10), and additional seminoma (n=11) for training purposes were included, split into training (N=78) and test cohorts (N=33). Lesions were lymph nodes (n=87), lung (n=21), and brain (n=3) with a median size of 1.6 cm (Q1-Q3 interval=1.2-2.73 cm). 3D Slicer version 5.6.1 was used to segment the RD > 1 cm (short axis) and extract radiomics features. Plasma miRNA levels before resection were measured by RT-PCR. Random Forest (RF), Support Vector Machine (SVM), Gradient Boosting (GB), and CatBoost (CB) ML models were evaluated to define the operating characteristics of radiomics alone (R-only) and in combination with miR371 (371) and/or miR375 (375) levels in predicting teratoma, vGCT and F/N. Results: For predicting teratoma, the best models were RF (R+375 and R+371+375), CB (R+371+375), and GB (R+371 and R+371+375). While adding miR371 or miR375 to R-only slightly improved AUC across models, the best results were achieved with the R+375+371 dataset. CB achieved AUCs ranging from 0.94 to 0.97 in training and 0.81 to 0.93 in test sets, with its highest AUC of 0.93 (95% CI: 0.78-0.97) on the R+375+371 dataset to differentiate all three classes. Similarly, GB demonstrated strong performance, achieving its highest AUC of 0.93 (95% CI: 0.79-0.96) on the R+375+371 dataset (Table). Conclusions: Integration of plasma miR371, miR375 and radiomics improved accuracy of predicting histologies across all ML models. These methods could be used to characterize the histology of RD in mNSTC patients to better inform treatment decisions. Further refinement, including incorporation of histological findings of the primary tumor, will be reported. AUC values of different ML algorithms on training and test sets. TRAINING SET TEST SET Model ±SD R R+375 R+371 R+375+371 Model (95% CI) R R+375 R+371 R+375+371 RF 0.93±0.05 0.95±0.04 0.95±0.03 0.96±0.04 RF 0.8(0.59-0.89) 0.85(0.72-0.93) 0.87(0.76-0.95) 0.91(0.78-0.95) SVM 0.84±0.06 0.84±0.09 0.89±0.11 0.89±0.09 SVM 0.72(0.54-0.80) 0.74(0.56-0.82) 0.83(0.69-0.92) 0.84(0.76-0.94) GB 0.94±0.04 0.91±0.08 0.95±0.05 0.97±0.03 GB 0.84(0.61-0.96) 0.89(0.77-0.97) 0.89(0.79-0.96) 0.93(0.79-0.96) CB 0.95±0.03 0.94±0.03 0.94±0.04 0.97±0.03 CB 0.81(0.6-0.93) 0.86(0.73-0.94) 0.89(0.78-0.97) 0.93(0.78-0.97)

509 Background: SWOG/CCTG S1823/GCC-001 is a non-interventional translational prospective cohort investigation with a primary endpoint of defining pre-treatment operational characteristics of the liquid germ cell cancer biomarker microRNA 371a-3p in predicting the presence of active germ cell malignancy. Opened in June 2020, 813 of the projected 956 patients have been registered with anticipated completion of accrual in early 2024. While analysis of the final endpoint awaits complete accrual and sufficient follow-up, S1823 creates a rich template of baseline clinical information and real-world treatment. Herein, we report baseline patterns of care in modern day real-world care delivery for Clinical Stage I (CSI) germ cell tumors across academic and community practices in North America. Methods: Data is obtained from case report forms and source documents for 547 S1823 enrollees with CSI seminoma or nonseminoma. Aggregate baseline clinical data unrelated to the primary endpoint are described to understand baseline clinical characteristics and management recommendations for CSI germ cell tumors. Results: Clinical characteristics and management recommendations for CSI are described in the table. The leading contributor to date is the Kaiser Permanente NCI NCORP followed by Canadian Institutions which together make up 38% of accruals from top level institutions. The majority of these largely young males were overweight or obese (67%). S1823 did not stipulate management which was at the discretion of local institutions/investigators. Active surveillance is the dominant strategy in both CSI seminoma and nonseminoma (85% overall). In CSI seminoma, adjuvant treatment with radiation is very rare (1/547) and adjuvant treatment with single agent carboplatin (1 or 2 cycles) is uncommon (4%). In CSI nonseminoma, adjuvant retroperitoneal lymph node dissection is also uncommon (3%) as is adjuvant chemotherapy with BEP X 1 or 2 (6%). Conclusions: In this large prospective multi-institutional observational cohort, surveillance appears to be the predominant management strategy for CSI germ cell tumors with very limited use of adjuvant chemotherapy or RPLND and virtual elimination of recommendation for radiation therapy for seminoma. Clinical trial information: NCT04435756 .[Table: see text]

Extensive research showcases the extent and efficacy of humor-based messaging in general health promotion. However, the work describing humor's use within testicular cancer (TC) awareness is less developed. The aim of this comparative critical review was to determine the impact of using humor-based messaging in TC awareness campaigns to achieve a baseline assessment from which future research can be modeled. A literature search was conducted using seven databases to locate relevant literature. Three research questions guided this investigation: (1) To what extent has humor been used in TC awareness campaigns? (2) What does the literature reveal about the use of humor-based messaging on relevant health outcomes? (3) What are the limitations within current TC awareness strategies? Six studies were included in the review, of which three directly assessed the use of humor in TC awareness vis-à-vis intervention designs. Humor-based strategies were implemented to enhance knowledge of TC and testicular self-examination (TSE) procedures, reduce anxiety surrounding detection threat, and promote TSE. The rhetoric provided to men via various health interventions relied on humor and slang to promote TSE among males. Despite the small sample size of the included studies, this review determined that humor may be useful in reducing uncomfortable feelings surrounding TSE, increasing awareness of TC, and promoting TSE. When using humor-based messaging, however, the audience and type of humor implemented must be considered. Limited research exists assessing the long-term impact humor in TC promotion on health behavioral changes, easing anxieties related to detection, and increased self-efficacy surrounding TSE.

We urge the United States Preventive Services Task Force (USPSTF) to call for aformal review of the evidence regarding testicular self-examination (TSE).Twelve years have since passed since the evidence was last formally analyzedwhere normally re-reviews occur in 5-year cycles. If they would decide to moveforward with this action, we ask for the USPSTF to review their methods forestablishing recommendations to optimize their rating system operationalizationprocess. Finally, emerging evidence demonstrates a net positive effect of TSE.This stands in contrast to the assertions of TSE’s supposed harm that isprevalent in the literature as well as the rationale behind the USPSTF’s “D”rating of TSE.

414 Background: Viable germ cell tumors (vGCT) express high levels of certain circulating microRNAs, including miR-371a-3p (miR371) that has shown high specificity and sensitivity. However, neither tissue nor serum/plasma from patients with only teratoma are miR371 positive. miR375 is overexpressed in teratoma tissue, but detectability in blood is unknown. Methods: miR371 and miR375 expression was analyzed in 100 patients with various stages and histology of GCT. miR375 expression in teratoma was validated in patients with post-chemotherapy pathologically confirmed teratoma (PCPCT). The miRNAs expression was assessed by RT-PCR and quantified by ΔΔCT method. The optimal cut-off for miR375 expression was estimated by Youden index ( > 20). Spike-in cel-miR-39-3p, miR-451 and miR-30b-5p were used as internal controls. Sensitivity, specificity, AUC of the ROC of miR375 in detecting teratoma was analyzed. Results: In the discovery cohort miR371 and miR375 were measured in 62 pts: 27 CSI NED, 15 chemo-naïve metastatic seminoma and 20 with PCPCT. miR375 was over-expressed in pts with teratoma compared to CSI and seminoma pts (p = 0.002), while miR371 was expressed in the seminoma pts and undetectable in the PCPCT and CSI pts (p < 0.001). In the post-chemotherapy setting, 38 pts were analyzed: 21 PCPCT, 6 vGCT and 11 complete remission (CR). Also in this cohort, miR375 was over-expressed in pts with teratoma compared to the pts presenting vGCT and post-chemotherapy CR (p = 0.01), while miR371 was detectable only in the pts with vGCT (p < 0.001). Overall, sensitivity and specificity of miR375 in identifying teratoma were 78% and 80%, respectively; the AUC was 0.7 (95% CI: 0.5490-0.8186; p < 0.01). Conclusions: Pts with residual post-chemotherapy teratoma present higher plasma levels of miR375 compared to pts with vGCT in whom miR375 is low but miR371 is expressed at high levels. The simultaneous evaluation of miR371 and miR375 may be clinically useful to predict the histology of the GCT components in pts with post-chemotherapy residual disease to inform the best therapeutic options (surgery or chemotherapy). Further validation within larger studies is warranted.

Testicular cancer (TCa) is the most prevalent neoplasm diagnosed in males aged 15–40 years. Lack of access to care is a key impediment to early-stage TCa diagnosis. Health equity concerns arise, however, as poor access largely manifests within underserved male populations, therefore, placing them at a higher risk to develop late-stage TCa. Planned Parenthood Federation of America (PPFA) offers a myriad of male reproductive/sexual health care options, including TCa screening and referral services. Therefore, expanding these amenities in traditionally underserved communities may address the concern of TCa screening opportunities. An ecological analysis was performed using data from the United States Cancer Statistics, American Community Survey, and PPFA databases to assess the impact of TCa upon minority males, identify associations between PPFA services and minority males, and provide future implications on the role PPFA may play in bridging health-care access gaps pertaining to TCa screenings. Results indicate that states with higher rates of poverty and uninsured individuals, as well as specifically Black/African American males, have lower TCa incidence and limited access to screening services. PPFA service presence and Black/African American, as well as uninsured, males had a negative association but revealed positive correlations with TCa incidence. Considering the emerging TCa outcome disparities among minority males, expanding PPFA men’s health services is crucial in providing affordable options to help identify testicular abnormalities that are early stage or carcinoma in situ. Many at-risk males have limited means to obtain TCa screening services. Expanding this discussion could provide a foundation for future advocacy.