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
SeminarRenal cancer
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
References (142)
- et al.
New modalities for evaluation and surveillance of complex renal cysts
J Urol
(2014) - et al.
Not all renal cysts are created equal
Lancet
(2010) - et al.
History of treated hypertension and diabetes mellitus and risk of renal cell cancer
Ann Oncol
(2007) - et al.
The epidemiology of renal cell carcinoma
Eur Urol
(2011) - et al.
Understanding pathologic variants of renal cell carcinoma: distilling therapeutic opportunities from biologic complexity
Eur Urol
(2015) - et al.
Distribution of metastatic sites in renal cell carcinoma: a population-based analysis
Ann Oncol
(2012) - et al.
Adrenal nodular hyperplasia in hereditary leiomyomatosis and renal cell cancer
J Urol
(2013) - et al.
Everolimus for renal angiomyolipoma in tuberous sclerosis
Lancet
(2013) - et al.
Recent advances in imaging cancer of the kidney and urinary tract
Surg Oncol Clin N Am
(2014) - et al.
EAU guidelines on renal cell carcinoma: 2014 update
Eur Urol
(2015)