Annals of Oncology Advance Access originally published online on July 22, 2008
Annals of Oncology 2008 19(9):1657-1658; doi:10.1093/annonc/mdn430
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letters to the editor |
Carcinomas of an unknown primary site: a curable disease?
introduction
Carcinomas of an unknown primary (CUP) are neoplasms with a notoriously poor prognosis. Median survival after the diagnosis is 
8 months and <25% of patients survive >1 year [1]. Favourable clinicopathological CUP entities have been defined [2, 3], and include (i) squamous cell carcinoma of the cervical lymph nodes, (ii) adenocarcinoma of the axillary lymph nodes in women, (iii) poorly differentiated carcinoma of the retroperitoneum or the mediastinum in young men, (iv) peritoneal serous papillary adenocarcinomatosis, (v) poorly differentiated carcinoma with neuroendocrine characteristics. Among patients whose disease does not correspond to these particular entities, favourable positive prognostic factors [3, 4] include a performance status (PS) of less than two and/or a normal serum lactate dehydrogenase (LDH) level. However, long-term survivors are usually not reported, even in large series of patients [4, 5] and whether cure can be achieved is still an open question. Here we report the cases of two patients with CUP who are long-term disease-free survivors after aggressive general and local treatments.
case 1
Mr S. consulted in December 1996 for a pain in the left arm. He had no past medical history except tobacco (20 packs/year) and alcohol (40 g/day) consumption. Clinical examination found a bulky left forearm mass and fixed enlarged lymph nodes (4 cm) in the supraclavicular and axillary area. PS was two and serum LDH was elevated (684 IU/l, normal upper value <600 IU/l). A total body computed tomography (CT) scan revealed no other abnormalities and a bone scan showed cancer lesions involving the L4 vertebra and left radius. A bone biopsy of the radius was carried out revealing a poorly differentiated carcinoma and immunohistochemical staining was positive for pan-cytokeratin (CK), membrane epithelial antigen, and negative for S100 protein. An en-bloc resection of the radial tumour was carried out followed by six cycles of cisplatin (100 mg/m2 on day 1) and etoposide (100 mg/m2 on days 1–3) repeated every 3 weeks. Treatment was completed with radiotherapy delivered to the lumbar area at a dose of 20 Gy and to the left arm at dose of 30 Gy. A complete clinical, biological and radiological response was achieved. The patient is progression free 8 years after the completion of treatment.
case 2
Mr D., 54, was referred in March 2002 for cervical adenopathies. He had a history of tobacco consumption (40 packs/year). He was in good general condition (PS = 0) and a complete examination including laryngoscopy, palpation of the testis and a rectal digital examination was normal. Serum CA19-9 and carcinoembyronic antigen were elevated and serum LDH was normal. A total body CT scan revealed no abnormalities apart from enlarged cervical lymph nodes and a doubtful pulmonary nodule. A biopsy of a cervical lymph node revealed a poorly differentiated adenocarcinoma and immunohistochemical staining was positive for CK 7 and negative for CKs 5–6, CK 20, HMB 45, S100 protein and TTF1. The patient received six cycles of cisplatin (100 mg/m2 on day 1) and gemcitabine (1000 mg/m2 on days 2 8), repeated every 3 weeks which resulted in a complete clinical, biological and radiological response. Postchemotherapy radiotherapy was delivered at a dose of 60 Gy to the supraclavicular, cervical and the right apex area. The patient is progression free >5 years after the completion of treatment.
discussion
Although none of these two patients belonged to the identified specific subgroups of CUP with a favourable outcome [2, 3], all are long-term progression-free survivors after aggressive local and systemic therapy. Of note, one of them had a predicted favourable outcome according to a validated prognostic model [3, 4]. However, the expected median survival is only about a year, even in patients with a good PS and a normal serum LDH. In large series of CUP, the proportion of long-term progression-free survivors (
3 after diagnosis) is <10% [4, 5]. In historical series, before the advent of chemotherapy, median survival was 4 months and no long-term survivors were reported [1]. Cases of long-term progression-free survivors have been increasingly reported in recent years in subjects with a variety of metastatic carcinomas, including notably metastatic colorectal and non-small-cell lung cancer. Our findings indicate that this result may also be achieved in patients with CUPs and it justifies treating these patients with chemotherapy, associated when feasible with aggressive local treatment.
Department of Medicine, Gustave Roussy Institute, Villejuif, France
* (E-mail: fizazi{at}igr.fr)
References
1. Pavlidis N, Fizazi K. Cancer of unknown primary (CUP). Crit Rev Oncol Hematol (2005) 54:243–250.[Web of Science][Medline]
2. Lenzi R, Hess KR, Abbruzzese JL, et al. Poorly differentiated carcinoma and poorly differentiated adenocarcinoma of unknown origin: favorable subsets of patients with unknown-primary carcinoma? J Clin Oncol (1997) 15:2056–2066.
3. Fizazi K. Treatment of patients with specific subsets of carcinoma of an unknown primary site. Ann Oncol (2006) 17:177–180.
4. Culine S, Kramar A, Fizazi K, et al. Development and validation of a prognostic model to predict the length of survival in patients with carcinomas of an unknown primary site. French Study Group on Carcinomas of Unknown Primary. J Clin Oncol (2002) 15(20):4679–4683.
5. Hess KR, Abbruzzese MC, Abbruzzese JL, et al. Classification and regression tree analysis of 1000 consecutive patients with unknown primary carcinoma. Clin Cancer Res (1999) 5:3403–3410.
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