Clinical outcomes of patients diagnosed with cancer of unknown primary or malignancy of undefined primary origin who were referred to a regional cancer center

Abstract

Background A regional cancer hospital has been identified to be crucial in the management of malignancies of undefined primary origin (MUO) and cancer of unknown primary (CUP). This hospital primarily consists of oncologists with expertise in CUP, pathologists, and interventional radiologists. Early consultation or referral of MUO and CUP to a cancer hospital is deemed important. Methods This study retrospectively collected and analyzed the clinical, pathological, and outcome data of all patients (n = 407) referred to the Aichi Cancer Center Hospital (ACCH) in Japan over an 8-year period. Results In total, 30% of patients were referred for a second opinion. Among 285 patients, 13% had non-neoplastic disease or confirmed primary site and 76% had confirmed CUP (cCUP), with 29% of cCUP being identified as favorable risk. In 155 patients with unfavorable-risk CUP, 73% had primary sites predicted by immunohistochemistry (IHC) and distribution of metastatic sites, whereas 66% of them received site-specific therapies based on the predicted primary sites. The median overall survival (OS) was found to be poor in patients with MUO (1 month) and provisional CUP (6 months). In addition, the median OS of 206 patients with cCUP treated at the ACCH was 16 months (favorable risk, 27 months; unfavorable risk, 12 months). No significant difference was noted in OS between patients with non-predictable and predictable primary-sites (13 vs 12 months, p = 0.411). Conclusion The outcome of patients with unfavorable-risk CUP remains to be poor. Site-specific therapy based on IHC is not recommended for all patients with unfavorable-risk CUP.

Retrospective analysis of clinical characteristics and outcomes of patients with carcinoma of unknown primary from three tertiary centers in Australia

“…At the dedicated Australian CUP clinic, only 31% of cases were assigned a likely site of origin, however this was based on clinicopathologic criteria for over half of these cases 16 . In a Japanese cohort, tissue of origin was assigned to 73% of patients based on an IHC panel alone 19 . These differences may relate to the strength of evidence needed to support tissue of origin assignment within a dedicated and multidisciplinary CUP clinic, compared to routine oncology practice.…”

“…In this study, 62% of patients underwent genomic profiling and 83% of patients received systemic therapy, with a median OS of 23.7 months in favorable risk patients compared to 10.9 months in unfavorable risk patients 16 . Patients in our study also had similar survival outcomes compared to other contemporary cohorts which have reported median OS ranging from 1.2–4 months for patients who did not receive treatment and 9.5–12 months for patients who did receive treatment 18–20 . Historical literature has reported a range of OS with palliative platinum‐based chemotherapy from 2.7 to 11 months in unfavorable risk patients 9,11–13 .…”

“…This is akin to the experience in the randomized GEFCAPI trial, where pancreaticobiliary tumors were the most assigned site, and no difference was found between site‐specific and empirical therapy 24 . Similar findings were also noted within a retrospective Japanese cohort, where a large proportion of patients were assigned an upper gastrointestinal site of origin 19 …”

“… 16 Patients in our study also had similar survival outcomes compared to other contemporary cohorts which have reported median OS ranging from 1.2–4 months for patients who did not receive treatment and 9.5–12 months for patients who did receive treatment. 18 , 19 , 20 Historical literature has reported a range of OS with palliative platinum‐based chemotherapy from 2.7 to 11 months in unfavorable risk patients. 9 , 11 , 12 , 13 Although this study only included patients who completed a standardized clinical workup, most of whom were of good performance status, survival outcomes remain poor.…”

“… 16 In a Japanese cohort, tissue of origin was assigned to 73% of patients based on an IHC panel alone. 19 These differences may relate to the strength of evidence needed to support tissue of origin assignment within a dedicated and multidisciplinary CUP clinic, compared to routine oncology practice. This data also corroborates other studies in the Australian jurisdiction, where oncologists may assign a tissue of origin without definitive evidence of a primary site in part so that the patient can obtain access to pharmaceutical treatment.…”