Cancers of unknown primary

Published on 09/04/2015 by admin

Filed under Hematology, Oncology and Palliative Medicine

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18 Cancers of unknown primary

TV. Ajithkumar, HM. Hatcher

Introduction

Cancers of unknown primary (CUP) constitute 3–5% of all cancers. The criteria for diagnosis of CUP includes patients who have a biopsy proven metastatic cancer in whom a detailed history, physical examination, blood tests, immunohistochemistry of biopsy, chest X-ray, CT scan of the abdomen and pelvis and in certain cases, mammography or FDG-PET fail to detect a primary tumour.

Evaluation

Clinicopathological evaluation aims to identify a primary site, a clinicopathological subset and to rule out non-epithelial tumours. The first step includes clinical history to establish risk factors, clinical examination, investigations and pathological evaluation. Initial investigations include blood tests, urinalysis, faecal occult blood test and CT scan of the chest, abdomen and thorax. Endoscopic evaluation is guided by symptoms and/or signs. In patients suspected to have extragonadal germ cell tumours a serum beta-hCG and AFP should be estimated. Other tumour markers depending on the clinical context include PSA, CEA, CA-125 and CA19-9. Pathological evaluation includes light microscopy and expedient use of immunohistochemical techniques. Immunohistochemistry is useful in differentiating epithelial from non-epithelial tumours, such as sarcoma and lymphoma (Table 18.1). The majority of epithelial tumours are adenocarcinoma (65–80%) followed by squamous cell carcinoma (10–15%) and undifferentiated carcinoma (5–10%).

Table 18.1 Immunohistochemistry in cancers of unknown primary

The outcome of first step evaluation is identification of a specific clinicopathological entity which may be a favourable (15% patients) or unfavourable (85% patients) (Box 18.1).

All patients should have an assessment of performance status and co-morbidities, which will guide treatment decisions.

Management

The decision to treat depends on the clinicopathological entity and performance status. Patients with poor performance status (>2) are generally treated symptomatically. Treatment of various subsets is as described below.

Women with isolated axillary lymphadenopathy

Women presenting like this are treated like stage II breast cancer. Previous studies showed an occult primary in 50–60% of cases after mastectomy. However, if MRI of the breast failed to show any primary, breast surgery or radiotherapy may not be warranted. Axillary lymphadenopathy is treated with lymph-node dissection followed by regional radiotherapy based on breast cancer radiotherapy principles (p. 124). Adjuvant systemic treatment is similar to stage II breast cancer. The reported 5-year survival for patients with 1–3 nodes are 87% and those with >3 nodes are 42%.

Women with peritoneal carcinomatosis

Women with peritoneal carcinomatosis are treated like stage III ovarian cancer with initial cytoreduction followed by combination chemotherapy or vice versa depending on performance status and co-morbidities (p. 201). CA-125 may be used as a tumour marker if elevated and the reported long-term survival is 15%.

Men with sclerotic metastasis

Men with sclerotic metastasis and with either raised serum PSA or immunohistochemical stain for PSA are treated with hormonal treatment for prostate cancer.

Single metastatic disease

Patients with single metastatic disease are treated with surgical excision or radical radiotherapy or combination. Role of systemic treatment is not known.

Cervical lymphadenopathy

Upper or mid-cervical lymphadenopathy can be due to a head and neck primary whereas lower cervical lymphadenopathy or supraclavicular lymphadenopathy can be due to either a head and neck cancer or lung tumour. Investigations using panendoscopy with CT/MR imaging will help to identify the primary site of the tumour in 85–90% of cases. If a lesion is not identified, unilateral tonsillectomy is done to rule out a tonsillar primary. PET scan may also be useful in identifying the primary. If a primary is detected it is treated accordingly with combined modality treatment with surgery and radiotherapy or chemo-radiotherapy. If no primary is detected, lymphadenopathy is treated with neck dissection followed by radiotherapy or radical radiotherapy. The reported 5-year survival ranges between 20–70%.

Patients presenting with inguinal lymphadenopathy

In this group of patients investigations are to rule out a primary site in the perineal area. If no primary tumour is detected, treatment is node dissection with or without postoperative radiotherapy.

Poorly differentiated carcinoma with midline distribution in young

These patients are usually male under 50 years of age, with mediastinal and/or retroperitoneal tumours. Serum beta-hCG and AFP estimation (raised in 20%), CT scan of chest, abdomen and pelvis and ultrasound of testis are needed. These patients are treated as poor prognostic germ cell tumours with four courses of BEP chemotherapy followed by surgical resection of any residual disease.

Poorly differentiated neuroendocrine carcinomas

These are treated with a combination of chemotherapy with cisplatin and etoposide which yields a response rate of over 70% with 16% durable remission based on a small series of 51 patients.

Poorly differentiated carcinoma without features of neuroendocrine or germ cell tumour

Patients with these tumours are in the good prognosis group and hence treated with a cisplatin regime like that used for germ cell tumours. In a study of 220 patients with median age of 39 years, the overall response rate was 64% with 27% complete response and median survival of 20 months.

Patients with unfavourable disease

Patients in the unfavourable subset are treated with symptomatic and palliative care. Those with good performance status are treated with chemotherapy with cisplatin-based or taxane/platinum combination which yields a response rate between 10–40% and median survival of 5–9 months.

Further reading

Pavlidis N, Fizazi K. Carcinoma of unknown primary (CUP). Crit Rev Oncol Hematol. 2009;69:271-278.

Greco FA, Erlander MG. Molecular classification of cancers of unknown primary site. Mol Diagn Ther. 2009;13:367-373.

Morris GJ, Greco FA, Hainsworth JD, et al. Cancer of unknown primary site. Semin Oncol. 2010;37:71-79.

Varadhachary GR, Abbruzzese JL, Lenzi R. Diagnostic strategies for unknown primary cancer. Cancer. 2004;100:1776-1785.

Pavlidis N, Briasoulis E, Pentheroudakis. Cancer of unknown primary site: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21(suppl 5):v228-v231.

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