Impact of Population Pharmacogenomics on Cisplatin-Induced Neurotoxicities in Testicular Cancer Survivors.

Background: Cisplatin is a commonly used chemotherapeutic across numerous cancer types that can cause neurotoxicities in patients, including peripheral sensory neuropathy, tinnitus, hearing loss, and vertigo.

Objective: We aimed to evaluate, for the first time, how genetic ancestry impacts cisplatin-induced neurotoxicities and if disparities are related to population differences in allele frequency.

Methods: In a cohort of cisplatin-treated testicular cancer survivors, relationships between genetic ancestry and neurotoxicities, medications, and lifestyle factors were assessed using logistic regression and Kruskal-Wallis tests and multiple pairwise comparisons using the Wilcoxon rank-sum test (Benjamini-Hochberg adjustment).

Optimal Management of Stage II Seminoma: Preventing Harm While Preserving Cure.

Stage II testicular seminoma is highly curable when treated using standard-of-care cisplatin-based chemotherapy or radiotherapy. However, these treatments can affect long-term quality of life because of the development long-term, or chronic, toxicities and late effects. In recent years, multiple emerging treatment strategies for stage II seminoma have been explored with the principal aim of minimizing toxicity in this young patient population.

Testicular cancer.

Testicular cancer is the most common solid malignancy in people with testicles aged 15-44 years, accounting for 1-2% of all tumours in males of all ages. Approximately 95% of testicular cancers are testicular germ cell tumours. This Seminar focuses on testicular cancer, with an emphasis on testicular germ cell tumours.

Impact of concomitant carcinoma in situ distribution on non-muscle-invasive bladder cancer progression risk.

Objective: To assess whether the distribution of concomitant carcinoma in situ (CIS; unifocal or multifocal) with papillary non-muscle-invasive bladder cancer (NMIBC) impacts the risk of progression, as concomitant CIS is an established risk factor for progression in papillary NMIBC and commonly used calculators do not make this distinction.

Patients And Methods: In this multi-institutional retrospective cohort study from both academic and community hospitals, clinicopathological data were collected from patients with pTa/pT1 NMIBC treated from 2005 to 2022. Unifocal concomitant CIS was defined as CIS present in only one specimen (i.

Prostate-specific antigen density does not predict metastatic disease on PSMA-PET in high-risk prostate cancer patients with negative conventional imaging.

Introduction: The ability of prostate-specific antigen density (PSAD) to predict metastatic disease on prostate-specific membrane antigen-positron emission tomography (PSMA-PET) at initial staging in high-risk prostate cancer (PCa) for men with negative conventional imaging is unclear. We hypothesized that there might be a PSAD cutoff below which PSMA-PET would be unnecessary, as it would so rarely identify metastatic disease.

Methods: A retrospective cohort study of all men receiving F-DCFPyl PSMA PET for primary staging between January 2018 and December 2022 at the University Health Network was performed.

Secondary malignancies after treatment of testicular germ cell tumors: a systematic review & meta-analysis.

Background: Testicular germ cell tumours (TGCTs) are the most common malignancy in men 15-35 years of age. Management options for men with TGCTs include surgery, radiation and/or chemotherapy. Given TGCTs' excellent survival, most patients live long enough to experience delayed treatment toxicities, warranting careful consideration of therapeutic decisions.

The association between statin use, genetic variation, and prostate cancer risk.

Background: The association between statin medication use and prostate cancer remains inconclusive. Evidence shows that genetic variation modifies lipid-lowering efficacy of statins, however, there are limited data on the pharmacogenomics of statins in prostate cancer chemoprevention.

Methods: Clinical and germline data were extracted from the prostate biopsy database at the University Health Network, Toronto, Canada (1996-2014).

Identification of genes associated with testicular germ cell tumor susceptibility through a transcriptome-wide association study.

Transcriptome-wide association studies (TWASs) have the potential to identify susceptibility genes associated with testicular germ cell tumors (TGCTs). We conducted a comprehensive TGCT TWAS by integrating genome-wide association study (GWAS) summary data with predicted expression models from normal testis, TGCT tissues, and a cross-tissue panel that encompasses shared regulatory features across 22 normal tissues, including the testis. Gene associations were evaluated while accounting for variant-level effects from GWASs, followed by fine-mapping analyses in regions exhibiting multiple TWAS signals, and finally supplemented by colocalization analysis.

Factors associated with longitudinal progression of the cumulative burden of morbidity and overall mortality after cisplatin-based chemotherapy for testicular cancer.

Background: To comprehensively evaluate the longitudinal progression of cumulative burden of morbidity (CBM) in testicular cancer survivors (TCS) following standard-dose cisplatin-chemotherapy and the impact of modifiable risk factors on morbidity and early-mortality.

Methods: Participants completed first-line chemotherapy ≥6 months before baseline assessments with comprehensive questionnaires and physical-examinations. Based on follow-up assessments (median: 7 years later), longitudinal progression of adverse health outcomes (AHOs) and CBM score (encompassing AHO number and severity) was examined.

Clinical Outcomes of Stage IIA/IIB Seminoma Treated With Radiation Therapy and Chemotherapy: Should Regional Therapy be Considered the Preferred Treatment Approach?

Purpose: The optimal management of patients with de novo clinical stage IIA/B (CSIIA/B) or relapsed CSIIA/B (Rel-CSIIA/B) seminoma remains debated because of a lack of randomized evidence. Here, we sought to evaluate outcomes after radiation therapy and chemotherapy in this setting.

Methods And Materials: A prospectively maintained single-institutional database was retrospectively queried for patients diagnosed between 1995 and 2016 with de novo or Rel-CSIIA/B.

Primary retroperitoneal lymph node dissection in clinical stage 2a/b non-seminomatous germ cell tumour.

Objectives: To reassess the role of primary retroperitoneal lymph node dissection (RPLND) in patients with marker-negative non-seminomatous germ cell tumour (NSGCT) clinical stage (CS) 2a, to explore results in patients with CS 2b and to evaluate surgical methods, recurrence, and adjuvant chemotherapy indications.

Materials And Methods: Data from 17 institutions were collected, comprising 305 men who underwent primary RPLND for CS 2 NSGCT. Regression analyses were conducted to predict histology in the RPLND specimen and disease-free survival (DFS).

Oncological Outcomes Following Robotic Postchemotherapy Retroperitoneal Lymph Node Dissection for Testicular Cancer: A Worldwide Multicenter Study.

Background And Objective: The feasibility and safety of a robotic approach for postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) in testicular cancer have been demonstrated, but data on long-term oncological outcomes of this procedure are limited. Our aim was to evaluate oncological outcomes following robotic PC-RPLND in this setting.

Methods: This retrospective cohort study included consecutive patients with testicular cancer treated with robotic PC-RPLND at 11 academic centers worldwide between 2011 and 2023.

Proportion of Gleason Score ≥8 Prostate Cancer on Biopsy and Tumor Aggressiveness in Matched Cohorts of East Asian and Non-East Asian Men.

Background: Historically, Asia had a lower prostate cancer (PCa) incidence and mortality compared with Western countries, but the gap is narrowing. Paradoxically, Asians have been reported to present with more advanced disease though more favorable outcomes. Despite PCa becoming an emerging health priority in East Asia, our knowledge remains limited.

Statin use and oncological outcomes in a propensity-matched cohort of nonmetastatic castration resistant prostate cancer patients of the ARAMIS trial.

Introduction: While observational studies suggest favorable associations between statin use and prostate cancer (CaP) outcomes, data from randomized-controlled trials remain inconclusive. Our study explores the relationship between statin use and survival outcomes in the context of the phase III ARAMIS study, a trial of darolutamide in the treatment of nonmetastatic castration-resistant prostate cancer.

Methods: We reviewed all 1,509 patients in the ARAMIS trial.

Practice patterns and predictors of treatment intensification in patients with metastatic castration-sensitive prostate cancer.

Introduction: Treatment intensification beyond androgen deprivation therapy (ADT) has shown survival benefit in patients with metastatic castration-sensitive prostate cancer (mCSPC). There is a need to better understand how these novel treatments fit in real-world practice.

Methods: Using electronic medical records and administrative data, a population-based, retrospective cohort study of patients diagnosed with de novo mCSPC between 2010 and 2020 in Alberta, Canada, and initiated on ADT was conducted.

Long-term Relapse and Survival in Clinical Stage I Testicular Teratoma.

Background And Objective: Studies in metastatic nonseminomatous germ-cell tumor (NSGCT) suggest that the presence of teratomatous elements in the primary tumor is a risk factor for poor survival. Many guidelines have extrapolated this observation and recommend adjuvant retroperitoneal lymph-node dissection (RPLND) even for clinical stage I (CSI) teratoma confined to the testicle. Our objective was to assess relapse-free survival (RFS), cancer-specific survival (CSS), overall survival (OS) among patients with CSI pure teratoma in comparison to CSI NSGCT.

Statin Concentration in Prostatic Tissue is Subtype- and Dose-dependent.

Objective: To evaluate for the first time, comparative serum and prostate tissue concentrations of lipophilic and hydrophilic statins.

Methods: After reviewing all patients who underwent radical prostatectomy between 1993 and 2019, we selected 80 patients taking atorvastatin (lipophilic) or rosuvastatin (hydrophilic) for cholesterol control and with available banked fresh-frozen tissue from the prostatectomy. Primary endpoint was serum and prostate statin concentration measured by HPLC-mass spectrometry analysis.

5-α Reductase Inhibitors and Prostate Cancer Mortality.

Importance: 5-alpha-reductase-inhibitors (5-ARIs) are approved for treating benign prostatic hyperplasia (BPH) and have been found to reduce prostate cancer (PCa) risk by 25%. However, trials also have shown 5-ARIs to be associated with high-grade PCa. Whether 5-ARIs increase mortality among those with a diagnosis of PCa remains unclear.

Cognitive function in long-term testicular cancer survivors: impact of modifiable factors.

No study has comprehensively examined associated factors (adverse health outcomes, health behaviors, and demographics) affecting cognitive function in long-term testicular cancer survivors (TC survivors). TC survivors given cisplatin-based chemotherapy completed comprehensive, validated surveys, including those that assessed cognition. Medical record abstraction provided cancer and treatment history.

Primary retroperitoneal lymph node dissection for metastatic non-seminomatous germ cell tumours: outcomes and adjuvant chemotherapy.

Objectives: To compare the outcomes and treatment burden of primary retroperitoneal lymph node dissection (pRPLND) alone versus pRPLND + adjuvant chemotherapy (AC) in patients with pathological stage II (PSII) non-seminomatous germ cell tumours (NSGCT).

Patients And Methods: Retrospective review of the Princess Margaret Cancer Center eTestes cancer database identified patients with PSII NSGCT after pRPLND between 1995 and 2020. The primary outcome was relapse-free survival (RFS).

MicroRNA for Prediction of Teratoma and Viable Germ Cell Tumor after Chemotherapy.

MicroRNAs (miRNAs) are emerging as highly sensitive and specific markers for testicular germ cell tumors (GCTs) across the spectrum of disease. However, their utility in specific clinical scenarios requires further study. Here, we review the current evidence for miRNAs as tumor markers for the evaluation of treatment response in patients undergoing chemotherapy for the treatment of advanced testicular GCT.