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.

Keywords: Cancer of unknown primary; Immunohistochemistry; Predicted primary site; Site-specific therapy; Unfavorable risk.

Fig. 1

An IHC panel for predicting primary sites (modified version of the previous study by Hasegawa H et al. [7]). The initial assessment was based on morphological features, such as adenocarcinoma, squamous cell carcinoma, and others. Furthermore, primary sites were speculated based on confirmatory immunohistochemistry using cancer-specific antibodies, taking into account of clinical history and the distribution of metastatic sites. IHC immunohistochemistry

Fig. 2

Study profile between July 2012 and December 2020. 407 patients with cancer of unknown primary (CUP) or metastatic malignant disease of unknown primary origin (MUO) were referred to the Aichi Cancer Center Hospital (ACCH). ^†Patient`s characteristics; male 59%, median age 65 years, range: 29–91 years, and eight patients were referred for only pathological review. ^††One patient was diagnosed with hemangioma of liver, and three with non-neoplastic disease. ^‡Patients were finally diagnosed with MUO after failing to undergo thorough examinations, and they had only received the best supportive care (n = 9), or radiotherapy (n = 3). ^‡‡ Patients diagnosed with provisional CUP at the referrer hospitals did not obtain additional examinations to confirm CUP due to poor general condition or complications or comorbidities, and they had only received the best supportive care (n = 7), radiotherapy (n = 4), and surgery for bone metastasis (n = 2). ^§Twelve patients received treatments at the referrer hospitals

Fig. 3

A Overall survival of 206 patients with cancer of unknown primary treated at the Aichi Cancer Center Hospital, according to risk subgroups. B Overall survival of 133 patients with unfavorable risk treated with systemic therapy, based on primary site prediction. CI confidence interval, NE not estimable, OS overall survival