The Diminishing Importance of Primary Site Identification in Cancer of Unknown Primary: A Canadian Single-Center Experience

Abstract

BackgroundCancer of unknown primary (CUP) describes patients with metastatic disease without an identified primary tumor site. Successful diagnosis and treatment of these patients remains difficult. Published guidelines on CUP have highlighted “favorable” subtype groups. We investigated a series of CUP patients to review adherence to guidelines, and identification of primary cancers or “favorable” subtypes.MethodsPatients with histologically confirmed CUP at an academic institution from 2012 to 2018 were identified. Patient demographics, tumor presentation, diagnostic work-up and treatment information were retrospectively collected from electronic data records for descriptive analysis and compared to published clinical guidelines. The primary endpoint was the proportion of patients where the primary site was identified. Multivariable logistic regression models were used to identify factors associated with primary site identification. Kaplan-Meier survival curves were used to determine factors associated with poorer OS.ResultsThree hundred and five patients were included with a median follow-up time of 4.3 months. Primary tumor sites were identified in 109 patients (37.5%), which was most commonly lung cancer (33%). Statistical analyses did not identify any demographic or initial presentation factors associated with identifying the primary or not. More diagnostic tests did not increase the likelihood of primary site identification (P=0.44). Patients with an identified primary did not have longer OS than other patients (median 5.2 months vs. 4.7 months, P=0.47). 57 patients (18.7%) who had a defined “favorable” subtype experienced superior OS (36.6 months vs. 3.8 months; P<0.0001). Further, patients with good prognostic status who followed published treatment guidelines had longer OS (17.6 months vs. 13.2 months; P=0.04).ConclusionsCUP remains a difficult cancer to diagnose and treat. These results suggest identifying the primary has less impact than anticipated, but particular efforts to identify patients with “favorable” subtypes of CUP is important prognostically.

Diagnostic Approaches for Neuroendocrine Neoplasms of Unknown Primary (NEN-UPs) and Their Prognostic Relevance—A Retrospective, Long-Term Single-Center Experience

“…Interestingly, we identified only several significant differences between patients with or without an identified primary tumor site with regard to the performance rates of certain diagnostic approaches. This is in line with a study performed by Wong and colleagues, investigating the role of diagnostic work-up in the identification of a primary tumor in a patient cohort with CUP of different histological backgrounds [41]. Referring to this, the authors could not find any statistically significant differences between patients with an identified or an unidentified primary.…”

Clinicopathological, molecular and prognostic characteristics of cancer of unknown primary in China: An analysis of 1420 cases

“…Comparisons of incidence rates according to patients' homogeneous origins, analysis of causes of death, and comparison of the relative survival time are essential for the recognition of primary sites and tracking the metastatic process and thus provide even more insights into CUP etiology and therapy. 14,15 In the United Kingdom, the National Institute for Clinical Excellence (NICE) published guidelines in 2010 and recommended that every hospital with a Cancer Centre should establish a CUP team, including an oncologist, a palliative care physician, and a specialist nurse. 16 Although the relevant guidelines have not been published in China, Fudan University Shanghai Cancer Center (FUSCC, Shanghai, China), which is one of the Chinese authoritative cancer specialist hospitals, has taken the lead in establishing the "Diagnosis and Treatment Center for Multiple or Unknown Primary Malignant Tumors", aiming to supply advice on appropriate investigations and multidisciplinary review of cases and help reach a working diagnosis from which to coordinate anticancerspecific treatments for CUP patients.…”

“…Moreover, an epidemiological study of CUP is crucial to the screening and diagnosis of cancer as well as cancer etiology. Comparisons of incidence rates according to patients' homogeneous origins, analysis of causes of death, and comparison of the relative survival time are essential for the recognition of primary sites and tracking the metastatic process and thus provide even more insights into CUP etiology and therapy 14,15 …”

Successful treatment using immunotherapy in combination with chemotherapy for metastatic squamous cell carcinoma of unknown primary origin with bulky abdominal mass

“…[ 6 ] The role of PET testing in identifying primary sites missed by conventional imaging and previously undiagnosed metastases has also been recognized, especially in head and neck cancer. [ 7 ] Gatalica et al [ 8 ] found that in 96% of cases, the use of immunohistochemistry, gene sequencing, and in situ hybridization may provide more accurate drug selection for CUP and, consequently, improve the survival of the patients.…”

“…The first examination to confirm CUP should include a comprehensive physical examination, basic blood and biochemical analysis, histological examination with immunohistochemistry staining, CT of the chest, abdomen, and pelvis, and endoscopic examination if necessary [6] . The role of PET testing in identifying primary sites missed by conventional imaging and previously undiagnosed metastases has also been recognized, especially in head and neck cancer [7] . Gatalica et al [8] found that in 96% of cases, the use of immunohistochemistry, gene sequencing, and in situ hybridization may provide more accurate drug selection for CUP and, consequently, improve the survival of the patients.…”