Reviewed: 3 August 2005

Refer a patient

Those patients who present with an apparent cancer of unknown primary, but in whom a definite diagnosis is eventually made, should receive appropriate specific treatment. Their prognosis will depend on the diagnosis and the availability of effective specific treatment and they will not be included in the rest of the discussion.

4.1 Special Situations

Some patients have clusters of findings suggesting a possible primary site and indicating a potentially fruitful approach to treatment.

1. Axillary node or lytic-blastic bone-dominant adenocarcinoma in a woman should be assumed to be breast carcinoma. Ipsilateral local treatment to the breast should be considered if the presentation was an axillary mass. Chemotherapy or hormonal treatment, appropriate for breast carcinoma, should be considered. 
2. Abdominal-pelvic adenocarcinomatosis in a woman should be treated as ovarian carcinoma if the CA-125 level is markedly elevated. Cisplatin-based chemotherapy may be appropriate. 
3. Adenocarcinoma of liver, lung, lymph nodes or retroperitoneum in a man, associated with blastic bone lesions, may be of prostatic origin. The PSA should be checked and anti-androgen therapy may be useful. 
4. The combination of a mid-line tumour, rapid growth, prior major response to irradiation, or negative CEA and lymphoma histochemical stains in a young man with a poorly differentiated carcinoma may be consistent with a marker-negative germ cell neoplasm and should prompt a trial of cisplatin-based chemotherapy. 
5. Squamous carcinoma of the inguinal nodes should prompt close inspection of the perineum and referral for consideration of radiotherapy.
6. Finally, an uncommon syndrome of carcinoma of the retroperitoneum, mediastinum, lungs or lymph nodes with pathologic findings suggestive of neuroendocrine tumour may respond well to combination chemotherapy including etoposide and cisplatin.

4. 2 Other Primary Unknown Cancer

Treatment should be carefully selected and need not necessarily include systemic anti-neoplastics to be appropriate. The clinician should consider whether localized problems such as pain, obstruction, bleeding, cough or skin erosion might be managed with localized treatment such as irradiation or surgery. Radical radiation therapy with curative intent is rarely given except in the case of metastatic squamous cell carcinoma confined to the neck nodes or inguinal nodes. Depending on the overall condition of the patient, a course of palliative radiotherapy may vary from a single fraction to a two week course with longer courses of fractionated treatment given under special circumstances. Patients presenting with emergency conditions such as spinal cord compression should be referred immediately upon recognition of the diagnosis for assessment and treatment on an emergency basis.

If empiric chemotherapy is considered, the clinician should first decide whether it is wise for a given individual. Patients with major co-morbid cardiovascular, metabolic or other diseases which are actively symptomatic may well deteriorate more quickly under the added stress of chemotherapy. Patients with poor performance status (bed or chair-ridden most of the day) are unlikely to respond to systemic chemotherapy. Cytotoxic agents should be reserved for those patients who are sufficiently young and fit to permit a reasonable judgment that the unavoidable toxicities of such agents are worth enduring for a 20%-30% chance of a short-lived remission. No available test or assay can better identify the patient likely to profit from chemotherapy than the clinician's thoughtful appraisal.

Many chemotherapy programs have been described for the empiric treatment of patients with cancers of unknown primary site. In phase II clinical trials response rates of 0-50% have been reported. Limited phase III data is available Monotherapy with mitomycin at a dose of 15 mg/m² for two doses only given one month apart with re-assessment for evidence of response is appropriate for patients over 60 years of age or unable to tolerate cisplatin-based chemotherapy. Cisplatin and etoposide combinations are likely appropriate for younger patients with good performance status. Clinical trials may be available. Consideration can be give to the use of a Taxane. Further treatment at a later date can be considered for the minority of patients that truly benefit. Second line chemotherapy is ineffective and unjustifiable unless an extraordinary response occurred after primary treatment.

4.3 Follow-up

Once therapy has been completed patients will return to their referring physicians for continued follow-up. Most patients should be seen on an intermittent basis to check for symptoms or findings of obvious progressive disease. Routine follow-up investigations would generally not be required unless the patient becomes symptomatic since the overall approach is palliative in nature.