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Eleni Efstathiou and Christopher J. Logothetis

With testicular cancer, a disease with a cure rate of 95%, the challenge is to restore quality of life to pretreatment levels and sustain it long-term. Although the implementation of guidelines and optimization of treatment modalities over the past years have served this purpose, some complications remain inevitable and experts are still challenged with late complications of outdated treatment standards. This article focuses on the late complications of cisplatin-based chemotherapy without disregarding those of currently applied infradiaphragmatic radiation. The most serious long-term complications of chemotherapy or radiotherapy are cardiovascular toxicity and second malignancies, as each has a 25-year risk of approximately 16%. Compared with the general population, risk for second malignancies remains significantly increased for at least 35 years after treatment. Chemotherapy-related cardiovascular toxicity is probably a result of both direct endothelial damage induced by cisplatin and indirect hormonal and metabolic changes. The increased incidence of the metabolic syndrome identified in long-term survivors is most likely associated with the lower testosterone levels reported. Cisplatin-based chemotherapy affects not only Leydig cells but also Sertoli and germ cells, resulting in infertility in 30% to 50% of testicular cancer patients treated with chemotherapy. Chronic neurotoxicity occurs in half of men, whereas permanent ototoxicity and some degree of renal function impairment occur in up to 30%. Pulmonary fibrosis, occurring in 5% to 10% of patients treated with bleomycin, is fatal in 1%. Although current treatment of advanced disease has changed its natural course, we are challenged by an increasing incidence of late relapse, an entity with a distinct tumor biology characterized by latency and chemoresistance.

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Stuart Atkinson, Raoul S. Concepcion, John A. McLane, Deborah Boldt-Houle and Eleni Efstathiou

Background: Achieving and maintaining effective testosterone (T) suppression is key to treatment of advanced prostate cancer (PCa), for which LHRH agonists are standard of care. Increasing evidence suggests maintaining very low T levels to <20 ng/dL with androgen deprivation therapy (ADT) is desirable and correlates with disease-specific survival in patients with advanced PCa. Consistent drug delivery is important in providing continuous T suppression throughout the course of treatment without T rising above castrate level (T breakthrough). However, T breakthrough may occur between administrations, especially if a subsequent dose is delayed. Contributing factors to late administrations may include scheduling challenges, shortage of available appointments, and increasing number of patients. While FDA approvals for ADT drugs are based on a 28-day month, insurers may mandate full calendar months between doses for reimbursement. This study explored timeliness of subsequent LHRH agonist administrations and its relationship with T breakthrough. Methods: A retrospective review of electronic medical records from January 1, 2007 and June 30, 2016 of 85,030 LHRH agonist administrations for PCa treatment was conducted to evaluate the percentage of late subsequent dosing and impact on frequencies of T breakthrough, defined as T>50 ng/dL. Late administrations were defined as those on or after day 33, 98, 129, and 195 for 1, 3, 4, and 6 month formulations, respectively. Results: 26.9% of all subsequent LHRH agonist administrations were late: 14.4% were ≤1 week late, 3.1% were between 1–2 weeks late, and 9.4% were >2 weeks late. While only 4% of T values exceeded 50 ng/dL when doses were administered early/on time, 21% of T values exceeded 50 ng/dL when administrations were late. Conclusions: Over a quarter of subsequent administrations were defined as late, leading to >20% incidence of T values exceeding 50 ng/dL. Considering the clinical benefits of maintaining effective T suppression throughout a course of ADT, clinicians should administer treatments within approved dosing instructions, routinely monitor T levels, and consider prescribing treatments with proven efficacy through the dosing interval to maintain T at castrate levels.