Tumor Microenvironment in Adrenocortical Carcinoma: Barrier to Immunotherapy Success?

Adrenocortical carcinoma is a rare malignancy with aggressive behavior, with up to 40% of patients presenting with metastases at the time of diagnosis. Both conventional chemotherapeutic regimens and novel immunotherapeutic agents, many of which are currently being tested in ongoing clinical trials, have yielded modest results so far, bringing the need for a deeper understanding of adrenal cancer behavior to the forefront. In the recent years, the tumor microenvironment has emerged as a major determinant of cancer response to immunotherapy and an increasing number of studies on other solid tumors have focused on manipulating the microenvironment in the favor of the host and discovering new potential target molecules. In the present review we aim to explore the characteristics of adrenocortical cancer’s microenvironment, highlighting the mechanisms of immune evasion responsible for the modest immunotherapeutic results, and identify novel potential strategies.

Symptom burden, functional status, and clinical outcomes of hospitalized patients with advanced genitourinary cancers.

42 Background: Patients with advanced genitourinary (GU) cancers are often hospitalized for complications of their cancer and symptom management. Yet, little is known about the symptom burden, functional status, and health care utilization of these patients. Methods: We prospectively enrolled patients with advanced cancer who experienced unplanned hospitalizations at an academic medical center. Upon admission, we asked patients to self-report their physical (Edmonton Symptom Assessment Scale-revised [ESAS-r]) and psychological (Patient Health Questionnaire-4 [PHQ-4]) symptoms. We also collected data from nursing assessments about impairments in activities of daily living (ADLs). We compared symptoms, functional impairment, readmissions, and overall survival (OS) between cancer types (dichotomizing GU cancers vs other cancer types) and within GU cancers (dichotomizing prostate cancer vs kidney/bladder/adrenal cancer) using univariate and multivariable regression analyses adjusted for age, sex, education, comorbidities, and time since advanced cancer diagnosis. Results: Among 971 patients enrolled, 106 (10.9%) had advanced GU cancers (39.6% prostate cancer, 32.1% kidney cancer, 25.5% bladder cancer, and 2.8% adrenal cancer). Compared to patients with other cancer types, patients with GU cancers were older (median: 69.0 vs 64.0 years, p < 0.001) and had more time since advanced cancer diagnosis (median: 14.0 vs 7.0 months, p < 0.001). In univariate analyses, a greater proportion of patients with GU cancers had an ADL impairment (57.5% vs 38.0%, p < 0.001) compared to other cancer types but the groups did not differ in their physical (Mean = 33.3 vs 32.6, p = 0.61) or depression (Mean = 4.1 vs 3.3, p = 0.05) symptoms. In multivariable models, patients with GU cancers had similar risk of readmission in 90 days (HR 1.31, p = 0.077), but worse survival (median OS: 102.0 days vs 133.5 days, p < 0.001; HR 1.27, p = 0.046). Within GU cancers, patients with kidney/bladder/adrenal cancer (vs. prostate cancer) were younger (median: 66.0 vs 74.0, p < 0.001) with less time since advanced cancer diagnosis (median: 9.0 vs 23.0 months, p = 0.012) but had no difference in symptoms or functional impairment. They were more likely to be admitted for symptom management (66% vs. 39% for prostate cancer, p = 0.026). Patients with kidney/bladder/adrenal cancer also had higher risk of readmission (HR 2.04, p = 0.043) but no difference in OS, compared to patients with prostate cancer. Conclusions: We found that hospitalized patients with advanced GU cancers had significantly greater functional impairment and worse survival compared to those with other cancer types, and those with kidney/bladder/adrenal cancer had significantly higher readmission risk compared to those with prostate cancer. These findings support the need to develop tailored supportive care for hospitalized patients with GU cancers.