Beyond first-line chemotherapy, there were few effective treatments for the uncommon and aggressive tumor known as metastatic adrenal cortical cancer (ACC). Unfortunately, 2nd line chemotherapy, which was widely used as treatment, had poor survival rates. There was a lack of information on results when using non-chemotherapeutic methods, such as immunotherapy.

The Princess Margaret Cancer Center treated metastatic ACC patients from 2002 to 2020 in a retrospective assessment. Patients who underwent any form of second-line treatment and beyond were noted. Data from the clinical and demographic domains were summarized using descriptive statistics. By using the Kaplan-Meier technique, overall survival (OS) and progression-free survival (PFS) were calculated. The log-rank test was used to compare survival results.

Out of 84 patients with metastatic ACC, 30 (20.7%) had de novo disease after receiving local decisive treatment, and 54 (37.2%) had recurrent disease. About 51 (60.7%) and 30 (58.8%) patients had first- and second-line systemic therapy, respectively. The median age was 49 years (36-58); 18 (60%) of the population were female; 14 (47%) had functioning tumors; and 4 (13.3%), 25(83.3%), and 1(3.3%) were, respectively, ECOG 0, 1, and 2. Out of 16 individuals, only one exhibited MMR deficiency, according to the evaluation. Thirteen patients (43.4%) had non-chemotherapy treatment (8- clinical trial, 4-sunitinib, 1-pembrolizumab), whereas 17 patients (56.6%) underwent chemotherapy (14-gemcitabine capecitabine, 1 gemcitabine, 2 etoposide doxorubicin, and cisplatin challenge). In 16 out of 22 (72.7%) patients for whom data were available, mitotane was continued. The two groups’ baseline characteristics and illness control rates (18% for chemotherapy vs. 31% for non-chemotherapy, P=0.46) were comparable. While the median OS with non-chemotherapy was numerically superior (6.6 months (4.9-13.1) vs. 10.2 months (5.9-22.7), P=0.08, the median PFS was comparable (2.6 months (2-4) and 3 months (1.7-4.5), P=0.48).

In comparison to chemotherapy, the study demonstrated better outcomes using non-chemotherapy techniques. Although it had to be proven in bigger research, non-chemotherapy techniques like immunotherapy and clinical trials should be taken into consideration where appropriate given the absence of randomized data demonstrating the superiority of chemotherapy.