Elsevier

The Lancet

Volume 387, Issue 10021, 27 February–4 March 2016, Pages 894-906
The Lancet

Seminar
Renal cancer

https://doi.org/10.1016/S0140-6736(15)00046-XGet rights and content

Summary

The diagnosis and management of renal cell carcinoma have changed remarkably rapidly. Although the incidence of renal cell carcinoma has been increasing, survival has improved substantially. As incidental diagnosis of small indolent cancers has become more frequent, active surveillance, robot-assisted nephron-sparing surgical techniques, and minimally invasive procedures, such as thermal ablation, have gained popularity. Despite progression in cancer control and survival, locally advanced disease and distant metastases are still diagnosed in a notable proportion of patients. An integrated management strategy that includes surgical debulking and systemic treatment with well established targeted biological drugs has improved the care of patients. Nevertheless, uncertainties, controversies, and research questions remain. Further advances are expected from translational and clinical studies.

Introduction

Abdominal imaging is used for many different medical disorders (eg, hypertension, diabetes) and, therefore, incidental detection of renal masses is becoming increasingly common. A renal mass might be merely a simple renal cyst that requires no treatment or follow-up,1 but in a notable proportion of cases masses are benign renal lesions (eg, angiomyolipomas or oncocytomas) or malignant renal cell carcinomas that might require additional procedures or interventions.2 Although most incidentally detected lesions are small low-grade tumours, up to 17% of all renal cell carcinomas have distant metastases at the time of diagnosis.3 In this heterogeneous clinical setting, developments in molecular biology, diagnostic techniques, surgery, and medical oncology are revolutionising the approach to this disease.

Section snippets

Epidemiology

In 2013, renal cell carcinoma was diagnosed in more than 350 000 people worldwide, which made it the seventh most common site for tumours, and this cancer is associated with more than 140 000 deaths per year.4 Incidence of renal cell carcinoma varies worldwide, being higher in developed countries than in developing countries (appendix). Incidence predominates in men, with the male-to-female ratio being 1·5:1·0, and peaks at age 60–70 years.5 Despite increased incidence overall, improvements in

Pathophysiology and genetics

Renal cell carcinoma comprises a heterogeneous group of cancers with different genetic and molecular alterations underlying the many documented histological subtypes.18 Clear-cell, papillary (types 1 and 2), and chromophobe are the most common solid renal cell carcinomas within the kidney and account for 85–90% of all renal malignancies.18 Less common cancers include papillary adenoma, multilocular cystic clear-cell carcinoma, hybrid oncocytic chromophobe tumour, carcinoma of the collecting

Diagnosis

With the expansion of routine imaging for many disorders, patients with renal cell carcinoma are increasingly being identified by chance. Only 30% of patients are diagnosed on the basis of symptoms. At all stages, renal cell carcinoma might produce multiple hormone-like or cytokine-like biologically active products that lead to clinically important paraneoplastic syndromes (table 1).31

The findings of routine diagnostic blood tests might be altered by renal cell carcinoma, but no change is

Management

Notwithstanding advances in the understanding of renal cell carcinoma biology, surgery remains the mainstay of curative treatment. Although radical nephrectomy was historically the standard of care for management of renal tumours, detection of small renal lesions44 and accumulating evidence that surgically induced chronic kidney disease can increase patients' morbidity45 have led to more conservative approaches.46 Specifically, nephron-sparing surgery, active surveillance, and minimally

Metastatic disease at diagnosis

Historically, patients with metastatic clear-cell renal cell carcinoma were treated with systemic therapy based on immune modulators, mainly interferon α and interleukin-2, but outcomes were only slightly improved.96 In a few cases these agents have led to T-cell-mediated tumour regression secondary to enhancement in lymphocyte mitogenesis, lymphocyte cytotoxicity, and activity of lymphokine-activated and natural killer cells.97 Immunotherapy with high-dose interleukin 2 has been associated

Controversies, uncertainties, and research questions

Despite progress in the understanding of renal cell carcinoma, uncertainties, controversies, and research questions remain. Advances are expected over the next few years from translational and clinical studies. Novel tissue and genetic markers are expected to improve accuracy of renal biopsy in characterising histology and disease aggressiveness at diagnosis (indolent mass vs clinically relevant malignancy). This approach could be crucial to the selection of patients who will benefit from

Conclusions

Renal cell carcinoma provides one of the best examples in oncology of how innovative basic research, novel clinical findings, and improved surgical techniques can converge to improve the care of patients. Alternative management strategies, such as active surveillance or cryotherapy, can be considered for an increasing number of patients. For patients who are candidates for surgical excision, the development of minimally invasive techniques, such as robot-assisted laparoscopic nephron-sparing

Search strategy and selection criteria

We identified data for this Seminar through searches of PubMed and Web of Science. We included papers in core clinical journals that described studies in adults and were published in English from 2004 to 2014. Search terms included “renal cancer” or “kidney cancer” in combination with the terms “epidemiology”, “genetics”, “pathophysiology”, “diagnosis”, “biopsy”, “treatment”, “surgery”, “active surveillance”, “medical therapy”, or “targeted therapy”. We also searched cited references from

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