Testicular Cancer

The imaging analysis will consist in obtaining quantitative measurements of lesion uptake on the pre- and post-LuPSMA RLT (lesion and whole-body SUVmax, SUVmean and tumor volume) at each time point on all PET/CT scans. PET metrics at the lesion- and whole-body level will be compared among different PET radiopharmaceuticals at the same time point, and changes over time will be assessed. All patients will be followed-up at our institution and clinical outcome will be correlated to the imaging analysis assessment.

Testicular cancer diagnosis and treatment, especially given its threat to sexuality and reproductive health, can be distressing in the formative period of young adulthood. Cohort studies reveal the prevalence of depressive symptoms in testicular cancer exceeds the general population. In fact, the majority of young adult cancer survivors will experience impairing, distressing, and modifiable physical, behavioral, and psychosocial adverse outcomes that persist long after the completion of primary medical treatment. These include psychological distress, impairment in the navigation and pursuit of life goals, persistent side effects, elevated risk of secondary malignancies and chronic illness, and biobehavioral burden (e.g., enhanced inflammation, dysregulated stress hormones) which influence morbidity and disease-related vulnerabilities. However, few targeted, effective interventions exist to assist young survivors in re-negotiating life goals and regulating cancer-related emotions and none focus on reducing the burden of morbidity via biobehavioral mechanisms. Young or "emerging" adulthood is a period marked by goal attainment. Chronic illness experienced as "off time" in the lifespan interrupts goal pursuits and threatens valued life directions. As young adults return to goal pursuits, re-entry to post-cancer life can be a critical point in the survivorship trajectory. Behavioral intervention at this time is well positioned to confer longer-term impact. Emergent from our group's preliminary research, we developed and pilot-tested Goal-focused Emotion-Regulation Therapy (GET) as a novel behavioral intervention to enhance self-regulation through improved goal navigation skills, improved sense of purpose, and better ability to regulate emotional responses in young adults with testicular cancer. GET is a promising candidate intervention to address the mechanisms likely complicating the resolution of cancer-related burden. Responsive the need for feasible, effective, and scalable interventions, we will randomly allocate 250 young adult (ages 18 -39) testicular cancer patients to 6 sessions of GET or ISL, and evaluate primary and secondary outcomes at baseline, post-treatment, 3-month follow-up, and 6-months follow-up. We predict that GET will be associated with superior distress outcomes and comparatively greater reductions in adverse biobehavioral indicators (dysregulated diurnal stress hormones, elevated systemic inflammation), and these advantages will be maintained at three- and six-months following intervention. The intervention will be delivered via an interactive video platform to enhance access. An additional exploratory aim focuses on potential epigenetic vulnerabilities, to understand how environmental influences (via DNA methylation) on genes implicated in stress reactivity and mood regulation are related to cancer adjustment and intervention response. This study capitalizes on the study team's unique expertise in biobehavioral oncology and salivary bioscience to test a novel behavioral intervention for young adult survivors. It has potential to understand how to alter proximal behavioral, biological, and psychological factors that underscore long term adverse effects.

Testicular cancer represents 1% of adult neoplasms and is the most common solid malignancy in young men. At diagnosis, approximately 90% of cases are germ cell tumours (GCT), categorised as either seminoma (55-60%) or non-seminoma types (40-45%). Approximately 20% of men with seminoma present with clinical stage (CS) II disease, characterized by enlarged retroperitoneal lymph nodes without distant metastasis. For many decades for patients who recur following CS 1 seminoma or present with de novo CS IIA/B seminoma, either radiotherapy (30-36Gy) or chemotherapy (BEPx3, EPx4) has been the mainstay of treatment. Yet, both treatment paradigms carry significant short and long-term treatment-related toxicities. Radiotherapy, when compared to surveillance or surgery alone, has been shown to double the risk of cardiovascular disease and secondary malignancies (with an incidence of 2-3%). Additionally, patients who receive chemotherapy for GCTs can develop complications including irreversible neurotoxicity (10%), ototoxicity (5-12%), pulmonary toxicity, which may result in permanent restrictive lung disease (8%), metabolic syndrome (10-16%), and hypogonadism (4%). Additionally, patients are at an approximate 3-7-fold increase in cardiovascular mortality and a two-fold increase in secondary solid malignancies and leukaemia. Furthermore, both treatment modalities can harm fertility potential by approximately 20-30%. However, in the past few years, a number of prospective single arm studies have been published evaluating the role of RPLND. RPLND is an appealing choice for patients with low-volume metastatic seminoma for several reasons: Firstly, seminoma exhibits a more indolent biological behaviour and a predictable lymphatic spread pattern compared to non-seminoma diseases, potentially allowing a greater chance of cure with surgery alone. Secondly, RPLND enables precise pathological staging which can avoid overtreatment in those with pathologically negative lymph nodes. It offers an opportunity to reduce the burden of chemotherapy by reserving this treatment only for the small proportion of men who will relapse following RPLND. Finally, RPLND offers an acceptably low risk of short or long-term complications when performed at experienced centres. Therefore, our objective is to prospectively evaluate the short and long-term safety and efficacy of Primary Retroperitoneal Lymph Node Dissection (RPLND) for patients with testicular seminoma and limited retroperitoneal lymph node metastasis.

Background: * Histological variants of the genitourinary (GU) tract include bladder/urachal adenocarcinoma, squamous cell carcinoma, and small cell carcinoma; variants of urothelial carcinoma including plasmacytoid, sarcomatoid; renal tumors including sarcomatoid renal cell carcinoma and renal medullary carcinoma; penile cancers; micropapillary, giant cell, lipid rich, clear cell and nested variants, large cell neuroendocrine carcinoma, lymphoepithelioma-like carcinoma and mixed patterns; small cell neuroendocrine carcinoma of the prostate, testicular Sertoli or Leydig cell tumors, and papillary and chromophobe renal cell carcinoma (RCC). * Some GU tumors occur so infrequently that they are not systematically captured by currently available registries, treatment protocols, or tissue banks. The rarity of these tumors limits the sufficient numbers of patients needed in larger randomized clinical studies to characterize standard treatments or disease course. * Systematic and longitudinal collection and annotation of clinical history, tissue samples, imaging studies, and other pertinent information in participants with these rare tumors will yield future knowledge and help with the development of subsequent prospective studies to optimize diagnosis and treatment paradigms for less common GU tumors. Objective: -Characterization of the natural history of urothelial and GU tract malignancies. Eligibility: -Participants \>= 18 years of age diagnosed with urothelial or GU tract malignancies. Design: * This will be a long-term multi-center study to comprehensively study participants with GU tumors. * Medical history will be collected, and participants followed throughout the course of their illnesses, with particular attention to patterns of disease presentation, recurrence and progression, response to therapies, and duration of responses. * Tissue samples and blood will be obtained from participants during this study. * A broad spectrum of scientific experiments, including genomics and immune monitoring will be performed. * We anticipate accruing 1000 participants on this protocol.

Prostate cancer is the second most common cancer in men and the fifth leading cause of male cancer-related death. Incidence rates are higher in developed countries (37.5 per 100,000) compared to developing countries (11.3 per 100,000), with similar patterns in mortality rates. Currently, approximately 10 million men are diagnosed with prostate cancer worldwide, with over 400,000 deaths annually. By 2040, annual mortality is projected to reach over 800,000. Detection methods for prostate cancer include digital rectal examination, serum prostate-specific antigen (PSA), ultrasound, CT, MRI, and bone scans. While helpful, these methods have limitations, particularly in early detection, biochemical recurrence, and post-treatment assessment. Hence, there is a pressing need for sensitive and specific diagnostic agents capable of detecting and localizing tumors and small metastases for accurate diagnosis, staging, and recurrence assessment. In recent years, PET molecular imaging, which visualizes biochemical metabolism and specific target expression, has provided valuable insights into tumor biology. Prostate-specific membrane antigen (PSMA), a type II glutamate carboxypeptidase produced by prostate epithelial cells, is highly expressed in prostate cancer and its metastases, with minimal expression in other normal tissues (e.g., intestines, brain, kidneys) at levels significantly lower than in cancer tissues. This specificity makes PSMA a crucial target for prostate cancer imaging. Two PET radiotracers, 68Ga-PSMA-11 and 18F-DCFPyL, are now FDA-approved in the United States for imaging prostate cancer, particularly for detecting recurrence. While these tracers offer high sensitivity and specificity, there are still some limitations. On the one hand, despite the high sensitivity of PSMA PET/CT, false positives can occur due to benign prostate hyperplasia, prostatitis, or other non-cancerous conditions that may also express PSMA. Additionally, some low-grade or small tumors, as well as neuroendocrine-differentiated prostate cancers, may not express sufficient PSMA, resulting in false negatives. On the other hand, PSMA PET/CT primarily detects PSMA-expressing tissues but does not provide information on other tumor biological characteristics, which may limit its utility in therapeutic decision-making and prognostic assessment. Trophoblast cell surface antigen 2 (Trop2) is another promising target, highly expressed in various cancers. Antibody-drug conjugates (ADCs) targeting Trop2 have demonstrated clinical success in treating advanced triple-negative breast cancer, HR+/HER2- breast cancer, and urothelial carcinoma, offering new options for patients with late-stage cancers resistant to multiple treatments. Since ADC efficacy is closely linked to antigen expression, Trop2 levels serve as a critical marker for predicting Trop2-ADC effectiveness. Currently, Trop2 detection is limited to immunohistochemical staining of biopsy samples, which reflects only local expression and cannot represent Trop2 levels across entire tumors or metastases. Thus, a comprehensive, in vivo, dynamic method for Trop2 expression detection is needed. Our research team has successfully developed a Trop2-specific nanobody and constructed a novel Trop2 PET probe labeled with 68Ga. This probe effectively identifies Trop2 expression in different tumor models, showing favorable pharmacokinetics and tumor uptake. Initial clinical research suggests that 68Ga-MY6439 demonstrates higher uptake in prostate cancer than 18F-FDG and 68Ga-PSMA-11 PET/CT, detecting more lesions in certain cases with increased diagnostic sensitivity. Therefore, beyond patient selection for Trop2-ADC therapy, Trop2-targeted PET probes have potential as broad-spectrum imaging agents for malignancies, aiding in the diagnosis, staging, and therapeutic monitoring of aggressive cancers, potentially overcoming limitations seen with 18F-FDG and 68Ga-PSMA-11 PET/CT in certain tumor types.

Participants in this research study, may or may not have a tumor within a urologic region of interest such as the bladder, prostate, testicle, kidney, urethra, and penis which may or may not have spread to a lymph node and have been scheduled to undergo a lymph node dissection procedure and/or organ removal surgery within one of the previously mentioned urologic regions of interest concerning for urologic cancer. This research study involves the use of a standard of care laparoscope and ultrasound probe. The laparoscope and ultrasound probe will have an electromagnetic sensor attached which will assist in the tracking of lymph nodes of interest or organs of interest. It is expected that the entire time to record the data will be less than 10 minutes. A total of 10 people will take part in this research study This study is supported by Siemens Medical USA.

The phase 1a Dose Escalation portion of the trial will enroll participants with PRROC, testicular, or endometrial cancer into one of approximately 9 dose escalation cohorts to assess safety, tolerability and to determine the recommended dose for expansion (RDE). CTIM-76 is to be administered once weekly (Q1W) for each cycle. A cycle is defined as 28 days. Participants will be dosed until documentation of disease progression, unacceptable toxicity, or participant/physician decision. The phase 1b dose expansion phase will evaluate CTIM-76 in at least one indication at up to 2 doses and/or dosing schedules (n=20 response evaluable participants in each cohort ) in the dose expansion phase of the trial (Phase 1b) studying one of the following advanced solid tumor types: PROC, testicular, or endometrial. This is to enable dose- and exposure-response analyses. The expansion doses/dosing schedules for Phase 1b will be determined by Sponsor in conjunction with Safety Review Committee (SRC) based upon all available safety, pharmacokinetic (PK), pharmacodynamic (PD), biomarker and preliminary efficacy data from Phase 1a. The selection of the RP2D will be based on the totality of data from Phase 1b.

Gastric cancer is the fifth most common cancer in the world and ranks fourth in mortality. Radical surgery is the main treatment for resectable gastric cancer. For patients with progressive gastric cancer, especially those with stage IIIB and IIIC, their 5-year overall survival (OS) rate after radical surgery is still difficult to exceed 50%. Although D2 radical surgery and postoperative adjuvant chemotherapy have significantly improved the prognosis of patients with progressive gastric cancer, the recurrence rate is still as high as 50%\~80%. Several therapeutic approaches have been established to reduce the risk of recurrence and improve long-term survival, including perioperative chemotherapy, adjuvant chemotherapy, and adjuvant radiotherapy. The effect of adding targeted therapies and/or immune checkpoint inhibitors (ICIs) to neoadjuvant/adjuvant therapies is currently being studied. While multiple programmed death 1 (PD-1) inhibitors have been approved for first/third line treatment of unresectable/metastatic gastric cancer. However, the role of immune checkpoint inhibitors in resectable gastric cancer remains unclear and is being investigated in various clinical trials. We conducted this study with 8 cycles of perioperative treatment with adebrelimab in combination with XELOX chemotherapy regimen and adebelizumab maintenance therapy up to 1 year. To observe and evaluate the efficacy and safety of adebrelimab combination chemotherapy regimen in the perioperative treatment of surgically resectable gastric cancer/adenocarcinoma of the gastroesophageal junction.

This is a observational cohort study to evaluate miRNA 371 in male patients with history of germ cell tumor or newly diagnosed germ cell tumor. Patients with newly diagnosed testicular germ cell cancers will be stratified in: 1. Low risk of relapse (5-25% chance of recurrence with active germ cell malignancy). Patients with low risk designation will be assigned to a low intensity schedule of biospecimen collection and imaging requirements. 2. Moderate risk of relapse (26-50% chance of recurrence). Patients with moderate risk designation will be assigned to a higher intensity schedule of biospecimen collection and imaging requirements including early repeat imaging and classic marker determination. The BRIDGE study evaluate the plasma expression of miRNA 371 as biomarker of relapse and its ability to detect germ cell malignancy within each of the early stage testicular seminoma and nonseminoma groups.

This is a single-arm, two-stage, Phase II study designed to evaluate the 6-month VTE-free rate in participants with advanced germ cell cancer at high risk of VTE who are receiving standard of care cisplatin-based chemotherapy and low-dose ASA as compared to relevant historical controls. Stage 1 will consist of 13 participants. If at least 9 of those 13 do not experience a VTE event during the first 26 weeks on the ASA, Stage 2 will be activated. Stage 2 will enroll an additional 18 participants for a total of 31. Participants will provide their own supply of ASA. Participants will self-administer a fixed dose of ASA (81 mg) by mouth daily for 26 weeks. Participants who experience the primary endpoint of VTE will stop ASA and start standard of care anticoagulation at the direction of the treating investigator. This study will initially open as a single center study at Atrium Health Wake Forest Baptist Comprehensive Cancer Center (AHWFBCCC) and additional investigational site(s) may be added following activation at the lead site.