Elsevier

The Lancet

Volume 352, Issue 9141, 21 November 1998, Pages 1691-1696
The Lancet

Seminar
Kidney cancer

https://doi.org/10.1016/S0140-6736(98)01041-1Get rights and content

Summary

In the USA, the incidence of kidney cancer has increased 43% since 1973. The risk of the disorder is higher in men than in women and increases with age. The von Hippel-Lindau tumour-suppressor gene is inactivated in over 75% of sporadic cases. Metastatic disease is present in 20–30% of patients at diagnosis. Early-stage kidney cancer is treated with a radical nephrectomy, but under certain circumstances a partial nephrectomy may be done. Tumour thrombus into the vena cava or right atrium requires thoracotomy and hypothermic circulatory arrest for successful removal of the tumour, but should not be done if extensive nodal or frank metastatic disease is present. Interleukin-2 is the systemic therapy of choice for metastatic disease at present, with long-term relapse-free survival of 5–8%. Several treatments including anti-angiogenesis drugs, cyclin-dependent kinase inhibitors, and differentiating agents are being actively investigated. Fluorouracil has a 10–15% response rate, and surgical excision of isolated metastases should always be considered. Therapy for metastatic renal cancer remains inadequate, but recent developments in basic and clinical research suggest future improvement.

Section snippets

Epidemiology

Men have a two to three times higher risk of the cancer than women.2 The median age at diagnosis is 65, but children are occasionally diagnosed with the disorder. The table shows that no single risk factor is dominant, and that several environmental or genetic factors could be synergistically carcinogenic (eg, smoking, obesity, hypertension).3, 4 Unusual associations between kidney cancer and other disorders have been reported, for example sickle-cell trait plus medullary kidney cancer in young

Genetics

Study of families with von Hippel-Lindau (VHL) disease,7 in which 25–45% of affected individuals develop kidney cancer, usually by the age of 50, has allowed identification of the genetic changes that lead to kidney cancer. Linkage of VHL to chromosome 3p, identification of a germline 3p chromosomal translocation in a non-VHL family with an unusually high number of kidney-cancer cases, and detection of 3p chromosomal deletions in sporadic clear-cell kidney cancer, led to the cloning of the VHL

Clinical presentation

Flank and back pain, fatigue, anaemia, haematuria, and weight loss are the most common presenting symptoms of kidney cancer. However, increasing numbers of apparently asymptomatic kidney cancers are diagnosed incidentally at radiography for other disorders.15 Cancers detected in this way have a good prognosis, but ultrasonographic screening of several large groups of people in Japan yielded low rates of incidental cancer diagnosis.16 Thus, routine ultrasonographic screening cannot be

Pathology

Pathological stage is better than clinical stage at predicting outcome. Careful pathological analysis will detect unusual renal neoplasms such as transitional-cell carcinoma, tumours of the duct of Bellini (collecting duct), oncocytoma, sarcoma, lymphoma, and adult Wilms' tumour, for which prognosis and management is distinct.23 The most common histological type of kidney cancer is clear-cell cancer (75% of cases). Most of these tumours arise from the proximal renal tubule and have inactivation

Treatment of the primary tumour

Routine formalin fixation and pathological interpretation are standard, but the primary tumour can also be studied with sophisticated molecular and cytogenetic tools.12, 13, 24 Lymphocytes, dendritic cells, and other host cells infiltrating the tumour can be isolated and expanded ex vivo. This process may give an opportunity for therapy.26 The tumour cells may provide antigens for vaccine therapy, currently available but in an early stage of development.27 Cell lines can be developed to

Adjuvant therapy of high-risk localised cancer

Given the high risk of recurrence in patients with stage II or III cancer at nephrectomy, adjuvant therapy may be required. To our knowledge, there have been four completed randomised trials of adjuvant immunotherapy for such patients. Galligioni and colleagues38 used subcutaneous injection of irradiated autologous tumour cells and intradermal BCG but did not show any disease-free or overall survival advantage for treated patients. Two trials of adjuvant interferon-α show no time-to-progression

Surgical resection

Several investigators have reported good long-term survival after surgical resection of metastatic cancer.36 Given the overall poor response rate to systemic therapy, resection should at least be considered. Most patients who benefit have only one metastatic site, usually a pulmonary, central-nervous-system, or bone site, and most have a long disease-free interval between initial nephrectomy and subsequent development of metastatic disease. However, the course of metastatic kidney cancer may be

Future prospects

Therapy for metastatic renal cancer remains inadequate. Active basic investigations to increase the response rate to immunotherapy include attempts to identify relevant tumour antigens75 such as herpes virus proteins that cause renal cancer in frogs,76 and to present these antigens to cells of appropriate types in the correct context to overcome the associated specific immunosuppression. Clinical studies are investigating use of immunostimulatory agents and gene-therapy techniques to modify

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