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Cancers of unknown primary site: ESMO Clinical Recommendations for diagnosis, treatment and follow-up

2009; Elsevier BV; Volume: 20; Linguagem: Inglês

10.1093/annonc/mdp159

1569-8041

Evangelos Briasoulis, Nicholas Pavlidis, Enriqueta Felip,

Genital Health and Disease

Cancers of unknown primary site (CUPs) represent a heterogeneous group of metastatic tumors for which a work-up as listed below fails to identify the site of origin at the time of diagnosis. CUPs accounts for 3–5% of all malignancies. CUPs require pathology evaluation and are categorized by pathology into:•well- and moderately differentiated adenocarcinomas;•poorly differentiated carcinomas;•squamous cell carcinomas;•undifferentiated neoplasms;•carcinomas with neuroendocrine differentiation. Immunohistochemistry should be applied in poorly differentiated cases to exclude chemosensitive and potentially curable tumors (i.e. lymphomas and germ cell tumors). If diagnosis is adenocarcinoma, immunostaining for prostate-specific antigen (PSA) in male patients and for estrogen and progesterone receptors in females with axillary node metastases is advisable to rule out hormone-sensitive tumors amenable to specific therapy. Staining for keratins CK7 and CK20 may provide indications towards a possible primary site. Appropriate staging and diagnostic work-up can help to identify a minority of CUP patients who can expect to benefit from directed therapy. The following recommendations epitomize standard and optional assessments suggested.•Thorough physical examination (including head and neck, rectal, pelvic and breast examination), basic blood and biochemistry survey, urinalysis, fecal occult blood test and CT scan of thorax, abdomen and pelvis constitute a minimal basic work-up.•Endoscopies should be sign- or symptom-guided. Serum assessment of α-fetoprotein (aFP), β-human chorionic gonadotropin (bHCG) and PSA is suggested in male patients to exclude potentially curable extragonadal germ cell tumor and amenable to hormone treatment prostate cancer.•A mammogram should be performed in women with an adenocarcinoma.•Whole body 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (CT/FDG-PET) may contribute to the management of patients with CUP tumors and especially those with cervical adenopathies and single metastasis.•Subsets of chemosensitive and potentially curable tumors, such as patients with predominantly nodal metastases of poorly differentiated carcinomas and females with peritoneal carcinomatosis of a serous histologic type adenocarcinoma must not be missed. Diagnostic and staging guidelines for patients with an anticipatory CUP diagnosis are summarized in Table 1.Table 1Diagnostic and staging guidelines for cancers of unknown primary siteAssessment suggestedTarget patient populationMinimal standard work-up Thorough medical history and physical examinationAll patients Basic blood and biochemistry surveyAll patients CT scans of thorax, abdomen and pelvisAll patientsWork-up for clinicopathological subsets Mammography or breast MRI (optional)Female with axillary adenopathy Serum α-fetoprotein and β-human chorionic gonadotropinPatients with midline metastastatic disease Serum prostate-specific antigenMale with adenocarcinoma bone metastases Head and neck CT scan or CT/PET scan (optional)Cervical adenopathies with squamous cell carcinoma EndoscopiesMust be sign or symptom oriented Open table in a new tab Therapy should be tailored on an individual basis by recognition of well-defined clinicopathologic subsets that differ in prognosis as described in Table 2 [III, B].Table 2Therapy of cancer of unkown primary siteCUP subtypeProposed treatmentPoorly differentiated carcinoma, predominantly nodal diseasePlatinum-based combination chemotherapyPoorly differentiated neuroendocrine carcinomasPlatinum plus etoposide combination chemotherapyPeritoneal carcinomatosis of a serous histologic type adenocarcinoma in femaleSimilar to FIGO III ovarian cancer: optimal surgical debulking followed by platinum chemotherapyIsolated axillary nodal metastases in femaleIdentical to patients with breast cancer and similar nodal involvementSquamous carcinoma involving cervical lymph nodesIrradiation for N1–2 disease. For advanced stages induction chemotherapy with platinum-based combination or chemoradiation is indicatedAdenocarcinoma with bone metastases and elevated prostate-specific antigen in malesHormonal therapy as for prostate cancerLiver, bone or multiple-site metastases of adenocarcinomaLow toxicity chemotherapy of palliative orientation or best supportive care Open table in a new tab Response evaluation is recommended after two or three chemotherapy cycles by individually adequate tests. There is no evidence that follow-up of asymptomatic patients is needed. Specific examinations as clinically indicated. Levels of evidence [I–V] and grades of recommendation [A–D] as used by the American Society of Clinical Oncology are given in square brackets. Statements without grading were considered justified standard clinical practice by the expert authors and the ESMO faculty.