Jump to content

Renal Cancer

Original Editors -Jason Larimore & Olivia Tefera from Bellarmine University's Pathophysiology of Complex Patient Problems project.

Top Contributors - Olivia Tefera, Jason Larimore, Angeliki Chorti, Lucinda hampton, Admin, Khloud Shreif, Elaine Lonnemann, Kim Jackson, WikiSysop, Vidya Acharya, 127.0.0.1 and Wendy Walker

Introduction

Renal or kidney cancer is an umbrella term for a very large and histologically heterogeneous group of tumours that start from the kidneys. [1]

Renal cancer may originate from:

  1. the epithelial cells of the renal parenchyma - this is renal cell carcinoma (RCC) or hypernephroma or Grawitz tumour, accounting for approximately 90% of all cases of kidney cancer [2]
  2. the renal pelvis, a form in the center of the kidney where urine collects, and then it's called transitional cell carcinoma of the renal pelvis, which behave like bladder cancers.[3][4]
  3. Renal sarcoma is another kidney tumor, but rare. [4]

Epidemiology

Renal cancers are responsible for over 131,000 fatalities and 342,000 new cases globally each year. [5] The majority of epidemiological research tends to concentrate on kidney cancer as a whole entity, leading to a scarcity of detailed information about the various histological subtypes.

RCCs are considered the 8th most prevalent cancer in adults, accounting for 2% of total cancer diagnoses and 80-90% of primary malignant tumors in adult kidneys. [5] Patients are typically 50-70 years of age at presentation with a moderate male predilection of 1.5:1, [2] [6] and greater prevalence in black men. [7] RCC may be sporadic in 96% and familiar in 4% of cases. [4]

Tumours originating from the renal pelvis are less common than RCCs and so do Wilms tumours in children - this type of cancer typically develops before the age of five; both displaying different epidemiologic patterns than RCCs. [8]

Renal sarcomas account for 0.25% of kidney cancers including 43 diverse histiotypes in epidemiology, presentation, and response to therapy.[9]Among renal sarcomas, leiomyosarcoma and malignant rhabdoid cancers are the most common. [9]

Risk Factors

Several risk factors for kidney cancer have been identified, with some being modifiable, thus presenting a chance for primary prevention. Unfortunately, there has been minimal progress in preventing and lessening the impact of kidney cancer to date. This has led to a greater need to find new ways to minimise exposure to risk factors and improve the prevention and early detection of this illness. [5]

Risk factors are grouped as follows:

  1. Lifestyle-Related Risk Factors: This includes smoking, obesity, alcohol use, lack of physical activity, and dietary choices.
  2. Medical History: Factors such as high blood pressure, chronic kidney conditions, kidney stones, cystic disease related to dialysis, cyclophosphamide treatment (a type of chemotherapy), post-kidney transplant, and diabetes.
  3. Environmental and Occupational Exposures: Exposure to substances like trichloroethylene and aristolochic acid (chemical compounds known for their health risks, especially in relation to cancer).
  4. Genetic risk factors and rare hereditary conditions.

[4][5][10]

Characteristics/Clinical Presentation

A classical presentation for patients with RCC includes the following triad:

  1. Macroscopic hematuria: 60%
  2. Flank pain: 40%
  3. Palpable flank mass: 30-40%

[6]

This triad is only found in 10-15% of patients with RCC; the remaining cases present with signs and symptoms related to the site of distant metastases. [11] That is why there are some cases discovered by chance with examination. [11] About 25-30% of patients have metastatic disease at the time of diagnosis.[12]

Renal cancer most often spreads to the lungs (75%), regional lymph nodes (65%), bones (40%), and liver (40%).[13] The patient may complain of a cough or bone pain secondary to metastasis to the lungs or bone, respectively.

[14]

The WHO Classification of Renal Cancer

Classification for kidney cancer was first attempted by the World Health Organisation (WHO) in 1981. [15] At the time, renal cell carcinoma (RCC) types were only included. Since then, several modifications have been made to the original version of the WHO classification, with the WHO 2022 Classification (5th edition) being the latest including six major epithelial groups and 21 histological subtypes. [16] [15][17]

The WHO 2022 classification of kidney cancers also includes The International Classification of Diseases for Oncology (ICD-O) topographical and ICD-O morphological coding, and the tumour, node, metastasis (TNM) staging (8th edition), for urological malignancies. [15]

Table 1 lists the WHO classification subtypes determined by molecular origin, morphology, immunohistochemistry, clinical data, epidemiology, and prognosis. [15]Clear cell, papillary and chromophobe RCCs account for more than 90% of RCC cases. [18]

Table 1.
Type Subtypes
1. Clear cell (ccRCC) [19] . Clear Cell Renal Cell Carcinoma

. Multilocular Cystic Renal Neoplasm of Low Malignant Potential

2. Papillary (pRCC) [20] . Renal Papillary Adenoma

. Papillary Renal Cell Carcinoma

3. Oncocytic and Chromophobe (crRCC) [21] . Oncocytoma of the Kidney

. Chromophobe Renal Cell Carcinoma . Other Oncocytic Tumours of the Kidney (LOT / EVT)

4.Collecting duct [22] . Collecting Duct Carcinoma
5. Other renal tumours . Clear Cell Papillary Renal Cell Tumour

. Mucinous Tubular and Spindle Cell Carcinoma .Tubocystic Renal Cell Carcinoma . Aquired Cystic Disease-Associated Renal Cell Carcinoma . Eosinophilic Solid and Cystic Renal Cell Carcinoma . Renal Cell Carcinoma, not otherwise specified

6. Molecularly Defined Renal Carcinomas . TFE3- rearranged Renal Cell Carcinoma

. TFEB-altered Renal Cell Carcinoma . ELOC (formely TCEB1)-mutated Renal Cell Carcinoma . Fumarate Hydratase (FH) - deficient Renal Cell Carcinoma . Succinate Dehydrogenase (SDH)- deficient Renal Cell Carcinoma . ALK- rearranged Renal Cell Carcinoma . SMARCB1-deficient Renal Medullary Carcinoma

7. Other
7a. Metanephric Tumours . Metanephric Adenoma

. Metanephric Adenofibroma

.Metanephric Stromal Tumour

7b. Mixed Epithelial and Stromal Renal Tumours . Mixed Epithelial and Stromal Tumour of the Kidney

. Adult Cystic Nephroma

7c. Embryonal Neoplasms of the Kidney . Neuroblastoma associated
7d. Renal Mesenchymal Tumours . Angiomyolipoma

. Renal haemangioblastoma . Juxtaglomerular Cell Tumour

. Renomedullary Interstitial Cell Tumour

7e. Miscellaneous Renal Tumours . Germ Cell Tumours of the Kidney
7f. Pediatric Renal Mesenchymal Tumours . Ossifying Renal Tumour of Infancy

. Congenial Mesoblastic Nephroma . Rhabdoid Tumour of Kidney . Clear Cell Sarcoma of Kidney

ICD-10-CM Codes

The 2026 ICD-10-CM Diagnosis Code for Renal Cancer is C64.9. Malignant neoplasm of unspecified kidney, except renal pelvis. (American Version from October 1st, 2025).

Grading

Histological nuclear grading:

The most widely used and most predictive grading system for renal cell cancer specially renal cell carcinoma is the "Fuhrman nuclear grade". The Fuhrman nuclear grade is a system used to classify the aggressiveness of kidney cancer, particularly renal cell carcinoma, based on the microscopic appearance of the cancer cells. It helps in determining the prognosis and potential treatment strategies for the disease with grade I and grade II, have a better prognosis and grade III and grade IV, suggest a poor prognosis as the following:

Renal cell carcinoma
  • Grade 1: Small, round, uniform nuclei, about 10 micrometers or smaller. Nucleoli absent or not clear at 400x magnification.
  • Grade 2: Nuclei slightly larger than Grade 1, up to 15 micrometers, mostly uniform with some shape irregularities. Nucleoli may be seen but not distinct at 400x magnification.
  • Grade 3: Larger, more irregular nuclei, over 15 micrometers. Nucleoli are clearly visible at 400x magnification.
  • Grade 4: Very large, irregularly shaped nuclei. Nucleoli are clearly visible, and cells may have multiple nuclei.

Diagnostic Tests & Investigation

Recurrent renal cell carcinoma.

The following tests and procedures may be used:

  • Physical exam and health history
  • Ultrasound exam
  • Blood tests: An unusual (higher or lower than normal) amount of a substance can be a sign of disease.
  • Urinalysis
  • DMSA
  • CT scan (CAT scan): A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
  • MRI (magnetic resonance imaging) - This procedure is also called nuclear magnetic resonance imaging (NMRI).
  • Biopsy - a thin needle is inserted into the tumor and a sample of tissue is withdrawn [23]

Prognosis

Prognosis for renal cancer may depend on various factors such as tumour type / grade, overall health, treatment effectiveness and most important, stage at diagnosis. [24] As a result, 5-year survival rates may range from 13% to 93% depending on how far the cancer has spread. Management of RCC has tremendously evolved in the last few years leading to better survival outcomes especially when detected early in localised and advanced disease. [25] However, treatment advances have also led to improved outcomes for metastasised kidney cancer, with the median survival reaching 5 years, according to a 2022 interview discussing promising updated survival data for metastatic RCC. [26]

Treatment Overview

Patients with renal cell cancer may work with a team of health care professionals to coordinate their care.eg Urologist, Surgeon, Urologic Oncologists, Medical Oncologists, Radiation Oncologists, Oncology Nurse, Registered Dietician. [27]

There are different types of treatment for patients with renal cell cancer. Five types of standard treatment are used:

  1. Surgery
  2. Radiation therapy
  3. Chemotherapy
  4. Immunotherapy
  5. Targeted therapy

RCC is primarily treated by surgical interventions. Although aggressive, a radical nephrectomy is the preferred method of treatment for both localised and metastasised disease. This consists of the removal of:

  • Kidney
  • Gerota’s fascia: fibroareolar tissue surrounding the kidney and perirenal fat
  • Adrenal gland
  • Regional lymph nodes

Kidney cancer, when diagnosed at a stage where it has already spread to other organs, is often not curable. The current standard treatment for such advanced stages of kidney cancer involves the use of targeted agents. [28]

Targeted therapies, which work by targeting the cancer at a cellular level, have expanded the options for the treatment of kidney cancer. Targeted treatments block specific abnormal signals present in kidney cancer cells that allow them to grow. These medications have shown promise in treating kidney cancer that has spread to other areas of the body. The targeted medications Axitinib (Inlyta), Bevacizumab (Avastin), Pazopanib (Votrient), Sorafenib (Nexavar) and Sunitinib (Sutent) block signals that play a role in the growth of blood vessels that provide nutrients to cancer cells and allow cancer cells to spread. Temsirolimus (Torisel) and Everolimus (Afinitor) are targeted medications that block a signal that allows cancer cells to grow and survive. Targeted therapy medications can cause serious side effects, such as: a severe rash, diarrhea, and fatigue

Whereas targeted therapies specifically block the renal cancer cells from growing and spreading, immunotherapy works in a more general way by using the body's immune system to fight the cancer. Immunotherapy medications include Interferon and Aldesleukin (Proleukin), which are synthetic versions of chemicals made in your body. Side effects of these medications include: chills, fever, nausea, vomiting and loss of appetite. [28]

Physical Therapy Management

Maintaining physical strength is important while undergoing renal cancer treatment and a physical therapist will be able to provide an exercise plan specifically designed for a patient’s needs.

  • If a patient had surgery to remove the tumor, modest exercise can help regain muscle tone and help to rebuild the muscles that were cut, increase that patient’s range of motion, and help to prevent complications that can occur post-surgery such as: respiratory infection, pressure sores, and the formation of a deep vein thrombosis (DVT).
  • Exercise can have the additional benefit of reducing stress and depression, which can be common occurrences in patients undergoing cancer treatment.
  • Physical therapy can also be used to combat fatigue, which is not only a common symptom of renal cancer but it can be a side effect of treatment (e.g. chemotherapy). Building up endurance can reduce the incidence and severity of fatigue. This will be an important factor in increasing a patient’s independence and ability to maintain a high quality of life.
  • Educate the patient regarding his or her diet, which will play an important role throughout the treatment process.
  • A systematic review and meta-analysis of randomised clinical trials suggested that intradialytic exercise protocols had positive outcomes in chronic kidney disease patients with poor cardiopulmonary function and reduced exercise tolerance and ventilatory efficiency. [29]

Case Reports/ Case Studies

Resources

European Association of Urology Guidelines on Renal Cell Carcinoma - 2025 update

National Cancer Institute.

NCCN Guidelines

Oncology

Oncology rehabilitation

Oncology and palliative care

Kidney Cancer Association

References

  1. ↑ Scelo G, Parker A, Banks RE, et al. Kidney cancer: Multiple risk factors, but currently limited preventive strategies. In: Wild CP, Weiderpass E, Stewart BW, editors. World Cancer Report: Cancer research for cancer prevention. Lyon (FR): International Agency for Research on Cancer; 2020. 5.16. Available from: https://www.ncbi.nlm.nih.gov/books/NBK606461/ [accessed 1/10/2025]
  2. ↑ 2.0 2.1 Bex A, Ghanem YA, Albiges L, Bonn S, Campi R, Capitanio U, Dabestani S, Hora M, Klatte T, Kuusk T, Lund L, Marconi L, Palumbo C, Pignot G, Powles T, Schouten N, Tran M, Volpe A, Bedke J. European Association of Urology Guidelines on Renal Cell Carcinoma: The 2025 Update. Eur Urol. 2025 Jun;87(6):683-96.
  3. ↑ Hsieh JJ, Purdue MP, Signoretti S, Swanton C, Albiges L, Schmidinger M, Heng DY, Larkin J, Ficarra V. Renal cell carcinoma. Nat Rev Dis Primers. 2017 Mar 9;3:17009.
  4. ↑ 4.0 4.1 4.2 4.3 Pandey J, Syed W. Renal Cancer. [Updated 2024 Oct 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK558975/ [accessed 1/10/2025]
  5. ↑ 5.0 5.1 5.2 5.3 Safiri S, Kolahi AA, Mansournia MA, Almasi-Hashiani A, Ashrafi-Asgarabad A, Sullman MJ, Bettampadi D, Qorbani M, Moradi-Lakeh M, Ardalan M, Mokdad A. The burden of kidney cancer and its attributable risk factors in 195 countries and territories, 1990–2017. Scientific Reports. 2020 Aug 17;10(1):13862.
  6. ↑ 6.0 6.1 Radiopedia. Renal cell carcinoma Available from:https://radiopaedia.org/articles/renal-cell-carcinoma-1 [accessed 1/10/2025]
  7. ↑ Lipworth L, Tarone RE, McLaughlin JK. The epidemiology of renal cell carcinoma. J Urol. 2006;176(6:2353-58.
  8. ↑ Scelo G, Larose TL. Epidemiology and Risk Factors for Kidney Cancer. J Clin Oncol. 2018 Oct 29;36(36):JCO2018791905.
  9. ↑ 9.0 9.1 Uhlig J, Uhlig A, Deshpande H, Ströbel P, Trojan L, Lotz J, Hurwitz M, Hafez O, Humphrey P, Grünwald V, Kim HS. Epidemiology, treatment and outcomes of primary renal sarcomas in adult patients. Sci Rep. 2024 May 2;14(1):10038.
  10. ↑ Nabi S, Kessler ER, Bernard B, Flaig TW, Lam ET. Renal cell carcinoma: a review of biology and pathophysiology. F1000Res. 2018 Mar 12;7:307.
  11. ↑ 11.0 11.1 Maestroni U, Gasparro D, Ziglioli F, Guarino G, Campobasso D. Metastatic clear cell renal cell carcinoma: the great pretender and the great dilemma. World J Oncol. 2021 Oct;12(5):178.
  12. ↑ Ljungberg B, Hanbury DC, Kuczyk MA, Merseburger AS, Mulders PF, Patard JJ, Sinescu IC; European Association of Urology Guideline Group for renal cell carcinoma. Renal cell carcinoma guideline. Eur Urol. 2007 Jun;51(6):1502-10.
  13. ↑ Goodman CC, Fuller KS. Pathology: Implications for the physical therapist. 3rd ed. St. Louis, Missouri: Saunders Elsevier, 2009.
  14. ↑ Dana-Farber Cancer Institute. Signs and Symptoms of a Kidney Tumor | Dana-Farber Cancer Institute. Available from: http://www.youtube.com/watch?v=Cq6PAVbquus[accessed 1/10/2025]
  15. ↑ 15.0 15.1 15.2 15.3 Goswami PR, Singh G, Patel T, Dave R. The WHO 2022 Classification of Renal Neoplasms (5th Edition): Salient Updates. Cureus. 2024 Apr 17;16(4):e58470.
  16. ↑ Netto GJ, Amin MB, Berney DM, Compérat EM, Gill AJ, Hartmann A, Menon S, Raspollini MR, Rubin MA, Srigley JR, Hoon Tan P, Tickoo SK, Tsuzuki T, Turajlic S, Cree I, Moch H. The 2022 World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs-Part B: Prostate and Urinary Tract Tumors. Eur Urol. 2022 Nov;82(5):469-482.
  17. ↑ Moch H, Amin MB, Berney DM, Compérat EM, Gill AJ, Hartmann A, Menon S, Raspollini MR, Rubin MA, Srigley JR, Hoon Tan P, Tickoo SK, Tsuzuki T, Turajlic S, Cree I, Netto GJ. The 2022 World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours. Eur Urol. 2022 Nov;82(5):458-468.
  18. ↑ Lopez-Beltran A, Carrasco JC, Cheng L, Scarpelli M, Kirkali Z, Montironi R. 2009 update on the classification of renal epithelial tumors in adults. Int J Urol. 2009 May;16(5):432-43.
  19. ↑ Weaver C, Bin Satter K, Richardson KP, Tran LKH, Tran PMH, Purohit S. Diagnostic and Prognostic Biomarkers in Renal Clear Cell Carcinoma. Biomedicines. 2022 Nov 17;10(11):2953.
  20. ↑ Muglia VF, Prando A. Renal cell carcinoma: histological classification and correlation with imaging findings. Radiol Bras. 2015 May-Jun;48(3):166-74.
  21. ↑ Muglia VF, Prando A. Renal cell carcinoma: histological classification and correlation with imaging findings. Radiol Bras. 2015 May;48:166-74.
  22. ↑ Panunzio A, Tappero S, Hohenhorst L, Cano Garcia C, Piccinelli M, Barletta F, Tian Z, Tafuri A, Briganti A, De Cobelli O, Chun FKH, Tilki D, Terrone C, Kapoor A, Saad F, Shariat SF, Cerruto MA, Antonelli A, Karakiewicz PI. Collecting duct carcinoma: Epidemiology, clinical characteristics and survival. Urol Oncol. 2023 Feb;41(2):110.e7-110.e14.
  23. ↑ Low G, Huang G, Fu W, Moloo Z, Girgis S. Review of renal cell carcinoma and its common subtypes in radiology. World J Radiol. 2016 May 5;8(5):484.
  24. ↑ Choi J, Bang S, Suh J, Choi CI, Song W, Yuk HD, Lee CH, Kang M, Choo SH, Kim JK, Lee HH, Jo JK, Hwang EC, Jeong CW, Ko YH, Park JY, Song C, Seo SI, Chung J, Kwak C, Hong SH. Survival pattern of metastatic renal cell carcinoma patients according to WHO/ISUP grade: a long-term multi-institutional study. Sci Rep. 2024 Feb 27;14(1):4740.
  25. ↑ Young M, Jackson-Spence F, Beltran L, Day E, Suarez C, Bex A, Powles T, Szabados B. Renal cell carcinoma. Lancet. 2024 Aug 3;404(10451):476-91.
  26. ↑ Targeted Oncology. Overall Survival Approaching 5 Years for Metastatic Renal Cell Carcinoma. Available from: https://www.targetedonc.com/view/overall-survival-approaching-5-years-for-metastatic-renal-cell-carcinoma [accessed 1/10/2025]
  27. ↑ National Cancer Institute. What you need to know about kidney cancer: Treatment. http://www.cancer.gov/cancertopics/wyntk/kidney/page8 (accessed 30 Jan 2013).
  28. ↑ 28.0 28.1 Unverzagt S, Moldenhauer I, Nothacker M, Rossmeissl D, Hadjinicolaou AV, Peinemann F, Greco F, Seliger B. Immunotherapy for metastatic renal cell carcinoma. Cochrane Database of Systematic Reviews. 2017(5).
  29. ↑ Andrade FP, Rezende PS, Ferreira TS, Borba GC, Müller AM, Rovedder PME. Effects of intradialytic exercise on cardiopulmonary capacity in chronic kidney disease: systematic review and meta-analysis of randomized clinical trials. Sci Rep. 2019 Dec 5;9(1):18470.

{{ 

Retrieved from "https://www.physio-pedia.com/w/index.php?title=Renal_Cancer&oldid=372759"