Patients\u27 Preferences for Androgen Deprivation Therapy in the Treatment of Intermediate-Risk Prostate Cancer

Background. For men with intermediate-risk prostate cancer (IRPC), adding short-term androgen deprivation therapy (ADT) to external beam radiation therapy (EBRT) has shown efficacy, but men are often reluctant to accept it because of its impact on quality of life. Methods. We conducted time tradeoffs (score of 1 = perfect health and 0 = death) and probability tradeoffs with patients aged 51 to 78 y who had received EBRT for IRPC within the past 2 y. Of 40 patients, 20 had received 6 mo of ADT and 20 had declined. Utility assessments explored 4 ADT-related side effects: hot flashes, fatigue, loss of libido/erectile dysfunction, and weight gain. Results. The most commonly reported “worst” treatment-related complication of ADT was fatigue (50% in both cohorts) followed by reduced libido/erectile dysfunction (40% in both cohorts). The utilities for fatigue were mean = 0.71 and median = 0.92 and for reduced libido/erectile dysfunction were mean = 0.81 and median = 0.92. Utilities did not differ significantly between cohorts. Assuming a 6-mo course of ADT, men reported being willing to trade 3 mo of life expectancy to avoid fatigue due to ADT and 1.8 mo to avoid sexual side effects. Patients in the ADT cohort were willing to accept the side effects of ADT in exchange for a mean 8% absolute increase in survival, whereas patients in the no ADT cohort required a 16% increase (P \u3c 0.001). Conclusions. When considering treatment with ADT, men with IRPC identified fatigue and sexual dysfunction as the most bothersome side effects. Patients who declined ADT expected a larger survival benefit than those who opted for treatment. Both groups expected a survival benefit exceeding that shown by recent trials, suggesting some men may be selecting treatments inconsistent with their preferences. Highlights This study demonstrates that prostate cancer patients receiving radiation therapy are reluctant to receive androgen deprivation therapy (ADT) most commonly due to anticipated fatigue and loss of libido/erectile dysfunction. Men who had received ADT reported they would require an average 8% absolute increase in survival to tolerate its side effects, whereas those who declined ADT would require an average 16% increase. Required thresholds are well above the estimated absolute survival benefit for ADT demonstrated in recent clinical trials, suggesting an unmet need for improved patient education regarding the risks and benefits of ADT

sj-docx-1-mpp-10.1177_23814683221137752 – Supplemental material for Patients’ Preferences for Androgen Deprivation Therapy in the Treatment of Intermediate-Risk Prostate Cancer

Supplemental material, sj-docx-1-mpp-10.1177_23814683221137752 for Patients’ Preferences for Androgen Deprivation Therapy in the Treatment of Intermediate-Risk Prostate Cancer by Brian De, Lisa M. Lowenstein, Kelsey L. Corrigan, Lauren M. Andring, Deborah A. Kuban, Scott B. Cantor, Robert J. Volk and Karen E. Hoffman in MDM Policy & Practice</p

Circulating neutrophils and tumor-associated myeloid cells function as a powerful biomarker for response to chemoradiation in locally advanced cervical cancer

Purpose: The immune system’s role in mediating the cytotoxic effects of chemoradiotherapy remains not completely understood. The integration of immunotherapies into treatment will require insight into features and timing of the immune microenvironment associated with treatment response. Here, we investigated the role of circulating neutrophils and tumor-associated myeloid cells (TSAMs) as potential agents and biomarkers for disease-related outcomes in locally advanced cervical cancer (LACC). Material and Methods: Hematologic parameters for two LACC patient cohorts, a retrospective clinical and a prospective translational cohort, were obtained at baseline, weekly during chemoradiotherapy for the retrospective cohort, biweekly during chemoradiotherapy for the prospective cohort, and at the first follow-up visit for both cohorts (mean 14.7 weeks, range 8.1–25.1 weeks for the prospective cohort and 5.3 weeks with a range of 2.7–9.0 weeks for the retrospective cohort). In both cohorts, baseline as well as mean and lowest on-treatment values for platelets, hemoglobin, absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) were analyzed for correlations with disease-related outcomes. In the prospective cohort, circulating myeloid cells were isolated from peripheral blood mononuclear cells (PBMCs), and TSAMs were isolated from tumor tissue via a novel serial cytobrush sampling assay. The samples were analyzed by flow cytometry. Results: In both cohorts, the only hematologic parameter significantly associated with survival was elevated on-treatment mean ANC (mANC), which was associated with lower local failure-free and overall survival rates in the retrospective and prospective cohorts, respectively. mANC was not associated with a difference in distant metastases. CD11b+CD11c- TSAMs, which act as a surrogate marker for intratumoral neutrophils, steadily decreased during the course of chemoRT and nadier’d at week 5 of treatment. Conversely, circulating myeloid cells identified from PBMCs steadily increased through week 5 of treatment. Regression analysis confirmed an inverse relationship between circulating myeloid cells and TSAMs at this time point. Conclusions: These findings identify on-treatment mean neutrophil count as a predictor of disease-related outcomes, suggest that neutrophils contribute to chemoradiation treatment resistance, and demonstrate the importance of techniques to measure intratumoral immune activity