Management of “unfavourable” carcinoma of unknown primary site: Synthesis of recent literature
Introduction
Carcinomas of unknown primary site (CUP) represent a group of heterogeneous tumours that share the unique characteristic of revealing metastases with no identifiable origin at the time of treatment [1], [2], [3]. There are histologically heterogeneous CUP subtypes, with adenocarcinoma (40–50%) and poorly differentiated carcinomas (30–40%) constituting the vast majority of cases. In the mid-1990s, approximately 50,000 cases of CUP were diagnosed in the United States of America, accounting for 5% of all adult cancers in Western countries. According to an epidemiological study, the incidence of CUP remains stable from 2002 to 2007 [4]. On the contrary, Greco et al. found that that number has been reduced by half due to the improvement of initial patient workup [6]. Currently, autopsy procedures of patients with CUP are able to identify the primary in approximately 60–80% of the cases, with the most common identified primaries being the following: lung, pancreas (both accounting for approximately 40% of identified primaries), other gastro-intestinal sites (colon, liver, biliary tree, etc.) and ovarian [6]. Nevertheless, despite recent improvements of modern imaging, functional imaging and immunohistochemistry, CUP still account for 2–3% of adult cancers [7], [8], [9]. Thus, the management of CUP patients remains a daily problem for clinical practice. In recent phase II trials, the median overall survival is approximately 8–12 months [7], [8], [9], [10], [11], but this figure could be partly due to the selection bias, so the respective roles of chemotherapy and best supportive care are still debated.
Recent guidelines based on the recently available data describe the ideal diagnostic management of revealing metastases and identifying specific subgroups of CUP requiring targeted approaches [3] (Table 1). Unfortunately, the vast majority (>80%) of CUP do not fit into these subsets. Based on a literature review, most physicians propose wide-spectrum empiric chemotherapy to these patients who do not fit the specific subsets. However, complete response or long-lasting stable disease in these patients is rare. Thus, the aim of the present review was to systematically analyse the clinical relevance of published prognostic scores and the results of phase II trials published in the last 15 years focusing on “unfavourable” CUP. This review updates two reviews published in Critical Reviews in Oncology/Hematology in 2005 [10] and 2009 [11].
Section snippets
Prognostic scores
Using Medline, we have systematically reviewed all articles related to the prognostic factors of CUP patients. We have compiled the data from the reprints of the studies, which account for at least 200 patients for whom the prognostic scores were validated on an independent cohort of patients. Four studies fulfilled these criteria and have been summarised in the present review.
Phase II clinical trials
Using Medline, we have reviewed all phase II clinical trials fulfilling the following criteria: (i) trials specifically
Prognostic scores
From the previous studies, four prognostic scores were developed [12], [13], [14], [15] and evaluated in independent cohorts [16] (Table 2). Three of these identified prognostic factors for overall survival [12], [13], [14] using Log-rank tests and then Cox models, whereas one identified the prognostic factors for early death (90-day mortality) using logistic regression analysis [13]. The prognostic models are different, but the scores are the combinations of up to 6 of the following prognostic
Discussion
Reviewing the recent literature on CUP management is a frustrating exercise. Currently, there are at least 4 formally validated prognostic models; however, none of the models is currently in practice or being used for the design of new clinical trials.
Due to the lack of sufficiently powered phase III trials, there are no definitive answers to questions related to CUP patient management. We have accumulated the results of decades of successive phase II trials. Most of these trials included both
Eric Yaovi Amela is a young physician born on May 1977 in the Togo and having studied Medicine at the Lille University. Graduate as general practitioner, he is physician at the Oscar Lambret Cancer Center. He currently acquires additional education and education to subspecialise in Oncology. His fields of expertise are testis and bladder cancers and carcinoma of unknown primary site.
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2021, Cancer Treatment ReviewsCitation Excerpt :In further lines, chemotherapy is for a very selected population, with no trials featuring best supportive care as a comparative arm. Response rates are usually around 10% with median OS ranging from 3 to 9.7 months [92]. If CUPs share a “biological signature”, they would behave similarly whatever their tissue of origin.
Pembrolizumab plus platinum-based chemotherapy for unfavorable cancer of unknown primary site: Case report
2020, Annals of Medicine and SurgeryCitation Excerpt :However, the median overall survival was 3–4 months in a cohort study that excluded a good prognosis group and these patients cannot receive effective treatment [8,9]. First-line chemotherapy with platinum- or taxane-based combinations is recommended for the poor prognosis group of CUP; however, the outcomes were unsatisfactory [1,2,10–14]. In our patient, we treated CUP as NSCLC due to adenocarcinoma localized to the mediastinum, TTF-1 positivity, and age higher than 50 years.
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Eric Yaovi Amela is a young physician born on May 1977 in the Togo and having studied Medicine at the Lille University. Graduate as general practitioner, he is physician at the Oscar Lambret Cancer Center. He currently acquires additional education and education to subspecialise in Oncology. His fields of expertise are testis and bladder cancers and carcinoma of unknown primary site.