دليل سرطان الخلايا الكلوية

ia_gov_sa · guide · processed · 22 chunks

Review Article
Saudi Oncology Society and Saudi Urology Association combined clinical management guidelines for renal cell carcinoma 2017
Abdullah Alsharm, Shouki Bazarbashi \( ^{1} \) , Abdullah Alghamdi \( ^{2} \) , Sultan Alkhateeb \( ^{3} \) , Ali Aljubran \( ^{1} \) , Ashraf Abusamra \( ^{4} \) , Hulayel Alharbi \( ^{5} \) , Mohammed Alotaibi \( ^{6} \) , Mubarak Almansour \( ^{7} \) , Hussein Alkushi \( ^{8} \) , Imran Ahmed \( ^{9} \) , Esam Murshid \( ^{10} \) , Amin Eltijani \( ^{11} \) , Danny Rabah \( ^{12} \)
Department of Medical Oncology, Comprehensive Cancer Center, King Fahad Medical City, \( {}^{1} \) Oncology Center, Section of Medical Oncology, King Faisal Specialist Hospital and Research Center, \( {}^{2} \) Department of Urology, Prince Sultan Military Medical City, \( {}^{3} \) Department of Surgery, Division of Urology, King Abdulaziz Medical City and King Saud bin Abdulaziz University for Health Sciences, \( {}^{6} \) Department of Urology, King Faisal Specialist Hospital and Research Center, \( {}^{10} \) Department of Oncology, Oncology Center, Prince Sultan Military Medical City, \( {}^{11} \) Department of Oncology, Division of Medical Oncology, King Abdulaziz Medical City and King Saud bin Abdulaziz University for Health Sciences, Riyadh, \( {}^{12} \) Department of Surgery, College of Medicine and Uro-Oncology Research Chair, King Saud University, Riyadh, \( {}^{5} \) Department of Medical Oncology, King Fahed Specialist Hospital, Dammam, \( {}^{4} \) Department of Surgery, Urology Section, King Khalid Hospital, King Abdulaziz Medical City, Departments of \( {}^{7} \) Oncology and \( {}^{8} \) Pathology, King Abdulaziz Medical City and King Saud bin Abdulaziz University for Health Sciences, \( {}^{9} \) Department of Oncology, Section of Medical Oncology, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia
Abstract
In this report, we update the previously published Saudi guidelines for the evaluation and medical and surgical management of renal cell carcinoma. It is categorized according to the stage of the disease using the tumor node metastasis staging system \( 7^{th} \) edition. The recommendations are presented with supporting evidence level.
Keywords: Guidelines, management, renal cell carcinoma, Saudi Oncology Society, Saudi Urological Association
Address for correspondence: Dr. Shouki Bazarabashi, Section of Medical Oncology, Oncology Center, King Faisal Specialist Hospital and Research Center, P.O Box 3354, Riyadh - 11211, Saudi Arabia.
E-mail: bazarbashi@gmail.com
Received: 18.11.2017, Accepted: 18.12.2017
INTRODUCTION
Renal cancer represents the \( 10^{th} \) most common cancer type in males ( \( 13^{th} \) most common cancer type in females) in the Saudi Arabian population. There were 313 cases of renal cancer in 2013, accounting for 2.7% of all newly diagnosed cancer cases. In 2013, the male-to-female ratio for this cancer was 1.6:1, and the age-standardized rate was
Access this article online
Quick Response Code:

Website:
www.urologyannals.com
DOI:
10.4103/UA.UA_175_17
2.9/100,000 for males and 1.7/100,000 for females. The median age at diagnosis was 56 years among males and 49 years among females. \( ^{[1]} \)
All cases of renal cell carcinoma (RCC) should preferably be seen or discussed in a multidisciplinary forum.
This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
For reprints contact: reprints@medknow.com
How to cite this article: Alsharm A, Bazarbashi S, Alghamdi A, Alkhateeb S, Aljubran A, Abusamra A, et al. Saudi oncology society and Saudi urology association combined clinical management guidelines for renal cell carcinoma 2017. Urol Ann 2018;10:123-32.
© 2018 Urology Annals | Published by Wolters Kluwer - Medknow
123

Alsharm, et al.: SOS and SUA guidelines for renal cell carcinoma
PRETREATMENT EVALUATION
Evaluation of suspicious renal mass
1. History and physical examination
2. Blood count, renal, and hepatic profiles
3. Computed tomography scan of the chest, abdomen, and pelvis
4. Urine analysis
5. Urine cytology should be done if urothelial cancer is suspected
6. Indications of renal mass biopsy include as follows: suspicion of renal abscess, suspicion of metastases, suspicion of renal lymphoma, and before systemic therapy. Furthermore, biopsy is strongly advocated before nonsurgical options (i.e., active surveillance, cryo [cryoablation], and radiofrequency ablation)
7. Brain imaging and bone scan should be done only if clinically indicated.
STAGING
The American Joint Committee on Cancer staging definitions for RCC should be adopted \( ^{[2]} \) [Tables 1 and 2].
PATHOLOGY
The recommended pathology report adopts the College of the American Pathologists 2016 Guidelines [Appendix 1].
TREATMENT
Localized disease (T1a)
1. The recommended treatment is surgical excision, preferably by partial nephrectomy (PN) (open,
laparoscopic, or robotic), in all cases, especially in patients with solitary kidney, bilateral tumors, familial renal cell cancer, or renal insufficiency (EL-1) [Figure 1] \( ^{[3-9]} \)
2. Radical nephrectomy (RN) (preferably laparoscopic) should be reserved for cases where PN is not technically feasible after consultation with an experienced surgeon (EL-1) \( ^{[3-16]} \)
3. Nonsurgical options (i.e., active surveillance,

Figure 1: Renal cell carcinoma management diagram
Table 1: Tumor, node, and metastasis staging for renal cell carcinoma
<table><tr><td>Primary tumor (T)</td><td>Regional lymph nodes (N)</td><td>Distant metastasis (M)</td></tr><tr><td>TX: Primary tumor cannot be assessedTO: No evidence of primary tumor</td><td>NX: Regional lymph node(s) cannot be assessedNO: No regional lymph node metastasis</td><td rowspan="2">M0: No distant metastasisM1: Distant metastasiscytology</td></tr><tr><td>T1: Tumor &lt;7 cm, limited to the kidneyT1a: Tumor &lt;4 cm, limited to the kidneyT1b: Tumor &gt;4 cm, but &lt;7 cm in greatest dimensionT2: Tumor &gt;7 cm in greatest dimension, limited to the kidneyT2a: Tumor &gt;7 cm but &lt;10 cm in greatest dimensionT2b: Tumor &gt;10 cm, limited to the kidneyT3: Tumor extends into major veins or directly invades adrenal gland or perinephric tissues but not into the ipsilateral adrenal gland and not beyond Gerota&#x27;s fasciaT3a: Tumor grossly extends into the renal vein or its segmental (muscle-containing) branches or tumor invades perirenal and/or renal sinus (peripelvic) fat but not beyond Gerota&#x27;s fasciaT3b: Tumor grossly extends into the vena cava below the diaphragmT3c: Tumor grossly extends into vena cava above the diaphragm or invades the wall of the vena CavaT4a: Tumor invades beyond Gerota&#x27;s fascia (including contiguous extension into the ipsilateral adrenal gland)</td><td>N1: Metastasis in a single regional lymph nodeN2: Metastasis in more than one regional lymph node</td><td>MO: No distant metastasisM1: Distant metastasiscytology</td></tr></table>
124
Urology Annals | Volume 10 | Issue 2 | April-June 2018

Alsharm, et al.: SOS and SUA guidelines for renal cell carcinoma
cryoablation, and radiofrequency ablation) are all inferior to surgical excision in terms of oncological outcome and are not recommended, except in patients with significant comorbidities that interdict surgical intervention (EL-2). \( ^{[17-21]} \)
Localized disease (T1b)
1. The recommended treatment is RN (preferably laparoscopic) (EL-1) \( ^{[10-16,22-27]} \)
2. PN may be an option, especially in patients with a solitary kidney, bilateral tumors, familial renal cell cancer, or renal insufficiency. However, this should only be performed by an experienced surgeon in a high-volume center (EL-1) \( ^{[22-29]} \)
3. Nonsurgical options (i.e., active surveillance, cryoablation, and radiofrequency ablation) are not recommended.
Localized disease (T2)
1. The recommended treatment is RN (EL-1) \( ^{[10-16,22-27]} \)
2. PN and nonsurgical options (i.e., active surveillance, cryoablation, and radiofrequency ablation) are not recommended.
Localized disease (T3)
1. The recommended treatment is RN with complete excision of all venous thrombus in the renal vein, inferior vena cava, and right atrium (EL-2) \( ^{[28,29]} \)
2. These surgeries should only be performed in a tertiary care centers with the availability of a cardiac, vascular, or hepatic surgeon, depending on the case (EL-2). \( ^{[28,29]} \)
Excision of the ipsilateral adrenal gland
1. Ipsilateral excision of the adrenal gland during RN is indicated in upper pole kidney tumors or the presence
Table 2: Renal cell carcinoma anatomical stages and prognostic groups
<table><tr><td>Stage grouping</td><td>T stage</td><td>N stage</td><td>M stage</td></tr><tr><td>Stage I</td><td>T1</td><td>N0</td><td>M0</td></tr><tr><td>Stage II</td><td>T2</td><td>N0</td><td>M0</td></tr><tr><td>Stage III</td><td>T3</td><td>N0</td><td>M0</td></tr><tr><td></td><td>T1–T3</td><td>N1</td><td>M0</td></tr><tr><td>Stage IV</td><td>T4</td><td>Any N</td><td>M0</td></tr><tr><td></td><td>Any T</td><td>N2</td><td>M0</td></tr><tr><td></td><td>Any T</td><td>Any N</td><td>M1</td></tr></table>
of a concurrent radiologically detectable adrenal gland lesion(s) (EL-2). \( ^{[30-33]} \)
Lymph node dissection
1. Resection of the regional lymph nodes (within Gerota's fascia) is an integral part of RN
2. Resection of the nonregional lymph nodes provides no therapeutic advantages but is used for staging purposes (EL-1). \( ^{[34]} \)
When doing PN, the surgeon should aim to obtain adequate surgical margin and avoid tumor inoculation, except in patients with von Hippel–Lindau syndrome. \( ^{[35-37]} \)
For postoperative follow-up after treatment, use the European Association of Urology Guidelines [Table 3].
Metastatic advanced, unresectable disease
1. For risk stratification of metastatic RCC, there are two valid options [Appendix 2]
i. The Memorial Sloan Kettering cancer center (MSKCC/Motzer) risk classification for metastatic disease \( ^{[38]} \)
ii. Heng Score for Metastatic RCC Prognosis. \( ^{[39]} \)
2. Potentially resectable primary tumors with solitary metastasis or multiple resectable lung metastases: these patients should undergo primary nephrectomy and resection of the metastatic lesion/s (EL-2). Following complete resection, no further therapy or “adjuvant therapy” is indicated (EL-3)
3. Potentially resectable primary and multiple nonresectable metastasis: those patients should undergo resection of the primary tumor if in good performance status (EL-1), \( ^{[40,41]} \) then start systemic therapy according to the following guidelines:
i. Clear cell histology with good or intermediate risk: options of therapy include systemic therapy with either sunitinib (EL-1), \( ^{[42]} \) bevacizumab and interferon \( \alpha \)-2a, or pazopanib (EL-1). \( ^{[4,43-45]} \) High-dose interleukin -2 may be used in highly selected patients and centers \( ^{[46]} \)
ii. Clear cell histology with poor risk: temsirolimus is the preferred treatment (EL-1). \( ^{[18,47]} \) An alternative option is sunitinib (EL-2)
iii. Nonclear cell histology: options of therapy include
Table 3: Surveillance guidelines following surgery for renal cell cancer, adapted from the European Association of Urology
<table><tr><td rowspan="2">Risk profile</td><td rowspan="2">Treatment</td><td colspan="8">Surveillance</td></tr><tr><td>6 months</td><td>1 year</td><td>2 years</td><td>3 years</td><td>4 years</td><td>5 years</td><td>After 5 years</td><td></td></tr><tr><td>Low</td><td>RN/PN</td><td>US</td><td>CT</td><td>US</td><td>CT</td><td>US</td><td>CT</td><td>Discharge</td><td></td></tr><tr><td>Intermediate</td><td>RN/PN/cryo/RFA</td><td>CT</td><td>US</td><td>CT</td><td>US</td><td>CT</td><td>CT</td><td>CT, alternate 2 years</td><td></td></tr><tr><td>High</td><td>RN/PN/cryo/RFA</td><td>CT</td><td>CT</td><td>CT</td><td>CT</td><td>CT</td><td>CT</td><td>CT, alternate 2 years</td><td></td></tr></table>
CT: Computed tomography, cryo: Cryoablation, PN: Partial nephrectomy, RFA: Radio frequency ablation, RN: Radical nephrectomy, US: Ultrasound
Urology Annals | Volume 10 | Issue 2 | April-June 2018
125

Alsharm, et al.: SOS and SUA guidelines for renal cell carcinoma
temsirolimus (EL-2), \( ^{[47]} \) sunitinib (EL-2), \( ^{[48]} \) or sorafenib (EL-2). \( ^{[49]} \) Medullary and collecting duct carcinomas should be treated with platinum-based chemotherapy (EL-3) \( ^{[50]} \)
iv. Unresectable primary tumor with or without metastatic disease: These patients with good performance status should be offered systemic therapy according to their histological results and MSKCC risk group as in Item 4.9.3
v. Recurrent disease postprimary nephrectomy: treatment will depend if resectable or not:
i. If resectable solitary metastasis: surgical resection should be attempted (EL-2). \( ^{[51-53]} \) No systemic therapy is of benefit following complete resection (EL-3)
ii. If nonresectable recurrence: patient should be treated as metastatic disease according to their histological results, using MSKCC Risk Score and/or Heng Score as in Item 4.9.3.
4. Second-line therapy posttyrosine tyrosine kinase inhibitor (TKI) failure: patients who fail with first-line TKIs should receive second-line therapy if in reasonable performance status. Options of second-line agents include: nivolumab (EL-1), \( ^{[54]} \) cabozantinib (EL-1), \( ^{[55]} \) or axitinib (EL-1). \( ^{[56]} \) In the absence of these options, everolimus can be considered \( ^{[57,58]} \)
5. Third-line therapy: consider everolimus (Level 3), sorafenib (Level 3), or clinical trials [Figure 1].
Financial support and sponsorship
Funding was provided by the Saudi Oncology Society for this work.
Conflicts of interest
There are no conflicts of interest.
REFERENCES
1. Saudi Cancer Registry. Annual Report; 2013. Available from: http://www.shc.gov.sa/Ar/HealthCenters/NCC/CancerRegistry/Pages/CancerRegistryRecords.aspx. [Last accessed on 2017 Jul 11].
2. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL. AJCC Cancer Staging Manual. 7 \( ^{th} \) ed. New York: Springer; 2010.
3. Gill IS, Kavoussi LR, Lane BR, Blute ML, Babineau D, Colombo JR Jr, et al. Comparison of 1,800 laparoscopic and open partial nephrectomies for single renal tumors. J Urol 2007;178:41-6.
4. Gong EM, Orvieto MA, Zorn KC, Lucioni A, Steinberg GD, Shalhav AL, et al. Comparison of laparoscopic and open partial nephrectomy in clinical T1a renal tumors. J Endourol 2008;22:953-7.
5. Kim SP, Murad MH, Thompson RH, Boorjian SA, Weight CJ, Han LC, et al. Comparative effectiveness for survival and renal function of partial and radical nephrectomy for localized renal tumors: A systematic review and meta-analysis. J Urol 2012. pii: S0022-5347(12)05254-8.
6. Lau WK, Blute ML, Weaver AL, Torres VE, Zincke H. Matched comparison of radical nephrectomy vs. nephron-sparing surgery in patients with unilateral renal cell carcinoma and a normal contralateral
kidney. Mayo Clin Proc 2000;75:1236-42.
7. Lee CT, Katz J, Shi W, Thaler HT, Reuter VE, Russo P, et al. Surgical management of renal tumors 4 cm. or less in a contemporary cohort. J Urol 2000;163:730-6.
8. Tan HJ, Norton EC, Ye Z, Hafez KS, Gore JL, Miller DC, et al. Long-term survival following partial vs. radical nephrectomy among older patients with early-stage kidney cancer. JAMA 2012;307:1629-35.
9. Van Poppel H, Da Pozzo L, Albrecht W, Matveev V, Bono A, Borkowski A, et al. A prospective, randomised EORTC intergroup phase 3 study comparing the oncologic outcome of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma. Eur Urol 2011;59:543-52.
10. Berger A, Brandina R, Atalla MA, Herati AS, Kamoi K, Aron M, et al. Laparoscopic radical nephrectomy for renal cell carcinoma: Oncological outcomes at 10 years or more. J Urol 2009;182:2172-6.
11. Burgess NA, Koo BC, Calvert RC, Hindmarsh A, Donaldson PJ, Rhodes M, et al. Randomized trial of laparoscopic v open nephrectomy. J Endourol 2007;21:610-3.
12. Gabr AH, Gdor Y, Strope SA, Roberts WW, Wolf JS Jr. Patient and pathologic correlates with perioperative and long-term outcomes of laparoscopic radical nephrectomy. Urology 2009;74:635-40.
13. Hemal AK, Kumar A. A prospective comparison of laparoscopic and robotic radical nephrectomy for T1-2N0M0 renal cell carcinoma. World J Urol 2009;27:89-94.
14. Hemal AK, Kumar A, Kumar R, Wadhwa P, Seth A, Gupta NP, et al. Laparoscopic versus open radical nephrectomy for large renal tumors: A long-term prospective comparison. J Urol 2007;177:862-6.
15. Luo JH, Zhou FJ, Xie D, Zhang ZL, Liao B, Zhao HW, et al. Analysis of long-term survival in patients with localized renal cell carcinoma: Laparoscopic versus open radical nephrectomy. World J Urol 2010;28:289-93.
16. Weight CJ, Lieser G, Larson BT, Gao T, Lane BR, Campbell SC, et al. Partial nephrectomy is associated with improved overall survival compared to radical nephrectomy in patients with unanticipated benign renal tumours. Eur Urol 2010;58:293-8.
17. Abouassaly R, Lane BR, Novick AC. Active surveillance of renal masses in elderly patients. J Urol 2008;180:505-8.
18. Chen DY, Uzzo RG. Optimal management of localized renal cell carcinoma: Surgery, ablation, or active surveillance. J Natl Compr Canc Netw 2009;7:635-42.
19. Kunkle DA, Uzzo RG. Cryoablation or radiofrequency ablation of the small renal mass: A meta-analysis. Cancer 2008;113:2671-80.
20. O'Malley RL, Berger AD, Kanofsky JA, Phillips CK, Stifelman M, Taneja SS, et al. A matched-cohort comparison of laparoscopic cryoablation and laparoscopic partial nephrectomy for treating renal masses. BJU Int 2007;99:395-8.
21. Rais-Bahrami S, Guzzo TJ, Jarrett TW, Kavoussi LR, Allaf ME. Incidentally discovered renal masses: Oncological and perioperative outcomes in patients with delayed surgical intervention. BJU Int 2009;103:1355-8.
22. Dash A, Vickers AJ, Schachter LR, Bach AM, Snyder ME, Russo P, et al. Comparison of outcomes in elective partial vs. radical nephrectomy for clear cell renal cell carcinoma of 4-7 cm. BJU Int 2006;97:939-45.
23. Leibovich BC, Blute M, Cheville JC, Lohse CM, Weaver AL, Zincke H, et al. Nephron sparing surgery for appropriately selected renal cell carcinoma between 4 and 7 cm results in outcome similar to radical nephrectomy. J Urol 2004;171:1066-70.
24. Peycelon M, Hupertan V, Comperat E, Renard-Penna R, Vaessen C, Conort P, et al. Long-term outcomes after nephron sparing surgery for renal cell carcinoma larger than 4 cm. J Urol 2009;181:35-41.
25. Simmons MN, Weight CJ, Gill IS. Laparoscopic radical versus partial nephrectomy for tumors >4 cm: Intermediate-term oncologic and functional outcomes. Urology 2009;73:1077-82.
26. Thompson RH, Siddiqui S, Lohse CM, Leibovich BC, Russo P, Blute ML, et al. Partial versus radical nephrectomy for 4 to 7 cm renal cortical tumors. J Urol 2009;182:2601-6.
126
Urology Annals | Volume 10 | Issue 2 | April-June 2018

Alsharm, et al.: SOS and SUA guidelines for renal cell carcinoma
27. Weight CJ, Larson BT, Gao T, Campbell SC, Lane BR, Kaouk JH, et al. Elective partial nephrectomy in patients with clinical T1b renal tumors is associated with improved overall survival. Urology 2010;76:631-7.
28. Eastham JA. Do high-volume hospitals and surgeons provide better care in urologic oncology? Urol Oncol 2009;27:417-21.
29. Joudi FN, Konety BR. The impact of provider volume on outcomes from urological cancer therapy. J Urol 2005;174:432-8.
30. Kuczyk M, Münch T, Machtens S, Bokemeyer C, Wefer A, Hartmann J, et al. The need for routine adrenalectomy during surgical treatment for renal cell cancer: The hannover experience. BJU Int 2002;89:517-22.
31. Kuczyk M, Wegener G, Jonas U. The therapeutic value of adrenalectomy in case of solitary metastatic spread originating from primary renal cell cancer. Eur Urol 2005;48:252-7.
32. Lane BR, Tiong HY, Campbell SC, Fergany AF, Weight CJ, Larson BT, et al. Management of the adrenal gland during partial nephrectomy. J Urol 2009;181:2430-6.
33. O'Malley RL, Godoy G, Kanofsky JA, Taneja SS. The necessity of adrenalectomy at the time of radical nephrectomy: A systematic review. J Urol 2009;181:2009-17.
34. Blom JH, van Poppel H, Maréchal JM, Jacqmin D, Schröder FH, de Prijck L, et al. Radical nephrectomy with and without lymph-node dissection: Final results of European Organization for Research and Treatment of Cancer (EORTC) randomized phase 3 trial 30881. Eur Urol 2009;55:28-34.
35. Blackley SK, Ladaga L, Woolfitt RA, Schellhammer PF. Ex situ study of the effectiveness of enucleation in patients with renal cell carcinoma. J Urol 1988;140:6-10.
36. Marshall FF, Taxy JB, Fishman EK, Chang R. The feasibility of surgical enucleation for renal cell carcinoma. J Urol 1986;135:231-4.
37. Rosenthal CL, Kraft R, Zingg EJ. Organ-preserving surgery in renal cell carcinoma: Tumor enucleation versus partial kidney resection. Eur Urol 1984;10:222-8.
38. Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J, et al. Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 1999;17:2530-40.
39. Heng DY, Xie W, Regan MM, Warren MA, Golshayan AR, Sahi C, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: Results from a large, multicenter study. J Clin Oncol 2009;27:5794-9.
40. Flanigan RC, Salmon SE, Blumenstein BA, Bearman SI, Roy V, McGrath PC, et al. Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med 2001;345:1655-9.
41. Mickisch GH, Garin A, van Poppel H, de Prijck L, Sylvester R; European Organisation for Research and Treatment of Cancer (EORTC) Genitourinary Group. Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: A randomised trial. Lancet 2001;358:966-70.
42. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007;356:115-24.
43. Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: A randomised, double-blind phase III trial. Lancet 2007;370:2103-11.
44. Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Ou SS,
et al. Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol 2008;26:5422-8.
45. Sternberg CN, Davis ID, Mardia J, Szczylik C, Lee E, Wagstaff J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: Results of a randomized phase III trial. J Clin Oncol 2010;28:1061-8.
46. Alva A, Daniels GA, Wong MK, Kaufman HL, Morse MA, McDermott DF, et al. Contemporary experience with high-dose interleukin-2 therapy and impact on survival in patients with metastatic melanoma and metastatic renal cell carcinoma. Cancer Immunol Immunother 2016;65:1533-44.
47. Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 2007;356:2271-81.
48. Armstrong AJ, Halabi S, Eisen T, Broderick S, Stadler WM, Jones RJ, et al. Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): A multicentre, open-label, randomised phase 2 trial. Lancet Oncol 2016;17:378-88.
49. Stadler W, Figlin R, Ernstoff M, Curti B, Pendergrass K, Srinivas S, et al. The Advanced Renal Cell Carcinoma Sorafenib (ARCCS) expanded access trial: Safety and efficacy in patients (pts) with non-clear cell (NCC) renal cell carcinoma (RCC). J Clin Oncol 2007;25 18 Suppl: 5036.
50. Oudard S, Banu E, Veillefond A, Fournier L, Priou F, Medioni J, et al. Prospective multicenter phase II study of gemcitabine plus platinum salt for metastatic collecting duct carcinoma: Results of a GETUG (Groupe d'etudes des tumeurs uro-génitales) study. J Urol 2007;177:1698-702.
51. Adam R, Chiche L, Aloia T, Elias D, Salmon R, Rivoire M, et al. Hepatic resection for noncolorectal nonendocrine liver metastases: Analysis of 1,452 patients and development of a prognostic model. Ann Surg 2006;244:524-35.
52. Kavolius JP, Mastorakos DP, Pavlovich C, Russo P, Burt ME, Brady MS, et al. Resection of metastatic renal cell carcinoma. J Clin Oncol 1998;16:2261-6.
53. Piltz S, Meimarakis G, Wichmann MW, Hatz R, Schildberg FW, Fuerst H, et al. Long-term results after pulmonary resection of renal cell carcinoma metastases. Ann Thorac Surg 2002;73:1082-7.
54. Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 2015;373:1803-13.
55. Choueiri TK, Escudier B, Powles T, Mainwaring PN, Rini BI, Donskov F, et al. Cabozantinib versus everolimus in advanced renal-cell carcinoma. N Engl J Med 2015;373:1814-23.
56. Motzer RJ, Escudier B, Tomczak P, Hutson TE, Michaelson MD, Negrier S, et al. Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: Overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol 2013;14:552-62.
57. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, et al. Phase 3 trial of everolimus for metastatic renal cell carcinoma: Final results and analysis of prognostic factors. Cancer 2010;116:4256-65.
58. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, et al. Efficacy of everolimus in advanced renal cell carcinoma: A double-blind, randomised, placebo-controlled phase III trial. Lancet 2008;372:449-56.
Urology Annals | Volume 10 | Issue 2 | April-June 2018
127

Alsharm, et al.: SOS and SUA guidelines for renal cell carcinoma
APPENDIX
Appendix 1: Sample pathology report
PROCEDURE
Partial nephrectomy
_ Radical nephrectomy
Other (specify): ____
Not specified
SPECIMEN LATERALITY
Right
Left
Not specified
+ TUMOR SITE (SELECT ALL THAT APPLY)
+ Upper pole
+ Middle
+ Lower pole
+ Other (specify): ____
+ Not specified
TUMOR SIZE (LARGEST TUMOR IF MULTIPLE)
Greatest dimension: ____ cm
+ Additional dimensions: ____ x ____ cm
____ Cannot be determined (see “Comment”)
TUMOR FOCALITY
Unifocal
Multifocal
MACROSCOPIC EXTENT OF TUMOR
Primary tumor cannot be assessed
No evidence of primary tumor
Tumor limited to kidney
Tumor extension into perinephric tissues
Tumor extension into renal sinus
Tumor extension beyond Gerota's fascia
128
Urology Annals | Volume 10 | Issue 2 | April-June 2018

Alsharm, et al.: SOS and SUA guidelines for renal cell carcinoma
____ Tumor extension into major veins (renal vein or its segmental (muscle containing) branches, inferior vena cava)
____ Tumor extension into pelvicaliceal system
+ Major calyx
+ Minor calyx
____ Tumor extension into adrenal gland
Direct invasion (T4)
Noncontiguous (M1)
____ Tumor extension into other organ(s)/structure(s) (specify): ____
Histologic Type
____ Clear cell renal cell carcinoma
____ Multilocular clear cell renal cell carcinoma
____ Papillary renal cell carcinoma
____ Chromophobe renal cell carcinoma
____ Carcinoma of the collecting ducts of Bellini
____ Renal medullary carcinoma
____ Translocation carcinoma (Xp11 or others)
____ Carcinoma associated with neuroblastoma
____ Mucinous tubular and spindle cell carcinoma
____ Tubulocystic renal cell carcinoma
____ Renal cell carcinoma, unclassified
____ Other (specify): ____
SARCOMATOID FEATURES
Not identified
Present
Specify percentage of sarcomatoid element: ____%
+ TUMOR NECROSIS (ANY AMOUNT)
+ ____ Not identified
+ ____ Present
HISTOLOGIC GRADE (FUHRMAN NUCLEAR GRADE)
Not applicable
GX: Cannot be assessed
G1: Nuclei round, uniform, approximately 10 \( \mu \) m; nucleoli inconspicuous or absent
Urology Annals | Volume 10 | Issue 2 | April-June 2018
129

Alsharm, et al.: SOS and SUA guidelines for renal cell carcinoma
G2: Nuclei slightly irregular, approximately 15 \( \mu \) m; nucleoli evident
G3: Nuclei very irregular, approximately 20 \( \mu \) m; nucleoli large and prominent
G4: Nuclei bizarre and multilobated, 20 \( \mu \) m or greater, nucleoli prominent, chromatin clumped
Other (specify): ____
MICROSCOPIC TUMOR EXTENSION (SELECT ALL THAT APPLY)
Primary tumor cannot be assessed
No evidence of primary tumor
TUMOR LIMITED TO KIDNEY
____ Tumor extension into perinephric tissue (beyond renal capsule)
____ Tumor extension into renal sinus
____ Tumor extension beyond Gerota's fascia
____ Tumor extension into major vein (renal vein or its segmental (muscle containing) branches, inferior vena cava)
____ Tumor extension into pelvicalyceal system
____ Tumor extension into adrenal gland
____ Direct invasion (T4)
____ Noncontiguous (M1)
____ Tumor extension into other organ(s)/structure(s) (specify): ____
MARGINS (SELECT ALL THAT APPLY)
____ Cannot be assessed
____ Margins uninvolved by invasive carcinoma
____ Margin(s) involved by invasive carcinoma
____ Renal parenchymal margin (partial nephrectomy only)
____ Renal capsular margin (partial nephrectomy only)
____ Perinephric fat margin (partial nephrectomy only)
____ Gerota's fascial margin
____ Renal vein margin
____ Ureteral margin
____ Other (specify): ____
+ LYMPH-VASCULAR INVASION
(excluding renal vein and its muscle containing segmental branches and inferior vena cava)
+ ____ Not identified
+ ____ Present
+ ____ Indeterminate
130
Urology Annals | Volume 10 | Issue 2 | April-June 2018

Alsharm, et al.: SOS and SUA guidelines for renal cell carcinoma
PATHOLOGIC STAGING (PTNM)
TNM Descriptors (required only if applicable) (select all that apply)
_ m (multiple primary tumors)
_ r (recurrent)
_ y (posttreatment)
PRIMARY TUMOR (PT)
__ pTX: Primary tumor cannot be assessed
__ pT0: No evidence of primary tumor
pT1: Tumor 7 cm or less in greatest dimension, limited to the kidney
__ pT1a: Tumor 4 cm or less in greatest dimension, limited to the kidney
__ pT1b: Tumor more than 4 cm but not more than 7 cm in greatest dimension, limited to the kidney
pT2: Tumor more than 7 cm in greatest dimension, limited to the kidney
__ pT2a: Tumor more than 7 cm but less than or equal to 10 cm in greatest dimension, limited to the kidney
__ pT2b: Tumor more than 10 cm, limited to the kidney
pT3: Tumor extends into major veins or perinephric tissues but not into the ipsilateral adrenal gland and not beyond Gerota's fascia
__ pT3a: Tumor grossly extends into the renal vein or its segmental (muscle containing) branches, or tumor invades perirenal and/or renal sinus fat but not beyond Gerota's fascia
__ pT3b: Tumor grossly extends into the vena cava below the diaphragm
__ pT3c: Tumor grossly extends into vena cava above diaphragm or invades the wall of the vena cava
__ pT4: Tumor invades beyond Gerota's fascia (including contiguous extension into the ipsilateral adrenal gland)
REGIONAL LYMPH NODES (PN)
__ pNX: Regional lymph nodes cannot be assessed
__ pN0: No regional lymph node metastasis
__ pN1: Metastasis in regional lymph node(s)
No nodes submitted or found
Number of Lymph Nodes Examined
Specify: ____
____ Number cannot be determined (explain): ____
Number of Lymph Nodes Involved
Specify: ____
____ Number cannot be determined (explain): ____
DISTANT METASTASIS (PM)
Not applicable
__ pM1: Distant metastasis
Urology Annals | Volume 10 | Issue 2 | April-June 2018
131

Alsharm, et al.: SOS and SUA guidelines for renal cell carcinoma
Appendix 2: Metastatic renal cell carcinoma prognostic models
MSKCC risk classification
<table><tr><td>Prognostic criteria</td></tr><tr><td>Time from diagnosis to treatment &lt;1 year</td></tr><tr><td>Hemoglobin &lt; lower limit of normal</td></tr><tr><td>Calcium &gt;10 mg/dl ( more than 2.5 mmol/L)</td></tr><tr><td>Lactate dehydrogenase &gt;1.5 x upper limit of normal</td></tr><tr><td>Karnofsky performance status &lt;80%</td></tr><tr><td>Risk stratification</td></tr><tr><td>favorable-risk group: No prognostic factors</td></tr><tr><td>Intermediate risk: 1 or 2 prognostic factors</td></tr><tr><td>Poor risk :3 prognostic factors</td></tr><tr><td>MSKCC: Memorial Sloan Kettering Cancer Center</td></tr></table>
Heng risk classification
<table><tr><td>Prognostic criteria</td></tr><tr><td>Time from diagnosis to systemic treatment &lt;1 year</td></tr><tr><td>Hemoglobin &lt; lower limit of normal</td></tr><tr><td>Calcium &gt;10 mg/dl ( more than 2.5 mmol/L)</td></tr><tr><td>Karnofsky performance &lt;than 80%</td></tr><tr><td>Neutrophil count &gt; upper limit of normal</td></tr><tr><td>Platelets count &gt; upper limit of normal</td></tr><tr><td>Risk stratification</td></tr><tr><td>favorable-risk group : no prognostic factors</td></tr><tr><td>Intermediate risk : 1 or 2 prognostic factors</td></tr><tr><td>Poor risk: 3 or more prognostic factors</td></tr></table>
132
Urology Annals | Volume 10 | Issue 2 | April-June 2018