Surgical Treatment of Renal Cell Carcinoma


According to the data obtained from the studies, renal cell carcinoma constitutes approximately 90% of 65,150 new cancer cases diagnosed and is also the main cause of 13,680 deaths in the year of 2013. Especially with recent advances in imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) and increasing access to these technologies, renal masses diagnosed with symptoms at the late stage have begun to be caught at much earlier stages. While the percentage of tumors diagnosed incidentally in 1970 ranged from 3% to 13%, this rate now ranges from 48% to 66%. However, approximately 20% to 30% of patients still have a metastatic disease at the time of initial diagnosis. Recurrence rates after surgical resection can reach up to 20% to 40% even in clinically localized renal carcinomas. In addition, relapse is a poor prognostic factor for long term survival.

Although new systemic targeted therapies have been developed in the last decade, these treatments are not able to provide long-term or complete responses, for now.

In the treatment of renal cell carcinoma, surgical treatment is the only long-term response that can provide complete cure. Surgical treatments include radical nephrectomy, partial nephrectomy (PN) or nephron-sparing surgery, ablative techniques, and metastasectomy in selected cases. All these treatments are actively used today in combination and with each other and also as multimodal.

In this article, all the options among surgical treatments of renal cell carcinoma will be discussed one by one.

1. Radical and Partial Nephrectomy

Radical nephrectomy and partial nephrectomy have become comparable with many retrospective series and one prospective randomized clinical trial study which including patients with organ-confined Renal Cell Carcinoma (RCC). [1]

a. Risks and renal functions

However, randomized control trials that can compare both approaches in terms of oncological safety are extremely limited and rare. Therefore, in this article information that based on the data obtained from the patients cohorts is given.

In addition, according to the results of these studies, it is thought that after the partial nephrectomy patients have better renal function and therefore, potentially reduce the risk of cardiovascular disease. [1, 2] Compared to radical surgical approaches, many retrospective analyzes with large databases claim that cardiac-specific mortality is reduced as well as improved overall survival (OS). [3]
However, in some studies it has been stated that this is true only in the young population and / or in patients who do not have serious comorbidities at the time of surgical intervention.[4, 5]

As a result of a study, partial nephrectomy was found to reduce clinically localized renal cell carcinoma deaths of any cause compared to radical nephrectomy, while serious adverse event rates, cancer-specific survival (CSS) rates and recurrence rates were similar between the two groups. [6]

b. Elderly populations

Today, the data in the large database cannot demonstrate the overall survival difference between treatment with radical nephrectomy or partial nephrectomy and non-surgical management in patients older than 75 years. [6]

It has been stated that other studies in this topic, which patients are also included in the medical databases, surgical treatment have contributed to overall survival compared to non-surgical management in patients with renal cell carcinoma in the elderly population. [7]

In another study, renal cell carcinoma patients treated with partial nephrectomy were compared with healthy people without cancer via retrospective database analysis, surgical treatment was found to be beneficial for overall survival (OS). [8]

These contradictory results may indicate that unknown statistical confusion hinders retrospective analysis of population-based tumor records.

In contrast to all, a prospective randomized study which prematurely closed and very weak, did not stated a priority between the radical nephrectomy and partial nephrectomy in the topic of overall survival (OS).

When all of them are evaluated together, it is still unknown whether partial nephrectomy or radical nephrectomy is more beneficial on overall survival.

In the medical literature, the majority of physicians think that after radical nephrectomy surgery, patients have a serious impairment of renal function and this has a bad effect on overall survival (OS). [208] Patients with preoperative normal renal function and decreased glomerular filtration rate (GFR) generally have stable long-term renal function. [9]

In contrast, pre-existing glomerular filtration rate (GFR) impairment and adverse overall survival (OS), however, do not appear to result from surgery on the kidneys, but from other medical comorbidities that cause pre-operative chronic kidney disease (CKD). [10]

In addition, partial nephrectomy is the most important treatment option in patients with pre-existing chronic kidney disease (CKD) to reduce the risk of end-stage renal disease (ESRD) which requires hemodialysis.

c. Quality of life

There are very few studies evaluating and comparing the quality of life after partial nephrectomy and radical nephrectomy. In these studies, no distinction was made between open and minimally invasive. According to the results of the studies, the quality of life of the patients after partial nephrectomy was found to be better than radical nephrectomy. However, after both surgical interventions, patients’ general health status is deteriorated. [11]

d. Morbidity and complications

Considering the intra- and perioperative complications and morbidities of radical nephrectomy and partial nephrectomy, there is no difference in length of hospital stay. [12] In addition, the number red blood cell (RBC) units applied and mean intraoperative blood loss are similar between two surgical approach. [13]

There are inconsistent reported complication rates for both surgical interventions in the medical literature. Although a longer operation time was reported for open partial nephrectomy, this information has not been confirmed by other studies. [14]

When all these data and oncological safety are evaluated, it can be said that there is not much difference between partial nephrectomy and radical nephrectomy. Therefore, partial nephrectomy is the surgical treatment of choice for Renal Cell Carcinoma (RCC) of stage T1. Because both kidney function can be better preserved and potential risks of cardiovascular disease are limited in the long term.

Although decreased mortality from any cause can be attributed to partial nephrectomy is still unresolved, it is the first surgical option to be preferred in patients with pre-existing chronic kidney disease (CKD). Because partial nephrectomy prevents further deterioration of renal function in these patients and reduces the risk of developing end-stage renal disease (ESRD) requires hemodialysis.

e. Survival outcomes

Another study in the medical literature compared the survival outcomes between partial nephrectomy and radical nephrectomy.

In patients with clear cell renal cell carcinoma (ccRCC) greater than 7 cm, partial radical nephrectomy treatment was found to have significantly longer median overall survival (OS) and cancer-specific survival (CSS) rates compared to the radical nephrectomy. [15]

According to the meta-analysis of the studies comparing the two surgical interventions, partial nephrectomy treatment in stage cT1b and stage T2 renal cell carcinomas (RCC) has lower tumor recurrence but also less cancer-specific survival (CSS), overall survival (OS) and all-cause mortality rates.

For stage T2 tumors, it is stated that the estimated blood loss was higher in partial nephrectomy operations as was the likelihood of complications. Also, in stage T2 renal cell carcinoma (RCC), both overall survival (OS) and cancer-specific mortality rates are lower for partial nephrectomy. [16]

f. Contraindications

Partial nephrectomy is unsuitable in some patients with localised renal cell carcinoma (RCC) due to:

  • insufficient volume of remaining parenchyma to maintain proper organ function;
  • renal vein thrombosis.

In these situations, the curative therapy is RN including removal of the tumour-bearing kidney. Complete resection of the primary tumour by open- or laparoscopic surgery offers a reasonable chance of cure.

2. Adrenalectomy

According to the results of the studies in the literature, upper pole location of the tumor is not a determining factor for adrenal involvement, while tumor size is an important marker.

In the presence or absence of adrenalectomy, there was no difference in overall survival rates at 5 and 10 years of follow-up. [17] Adrenalectomy was justified using criteria based on radiographic and intraoperative findings. Only 48 of 2,065 patients underwent concurrent ipsilateral adrenalectomy; 42 of these procedures were performed for benign lesions. [17]

In the literature, there is no clear information about cancer-specific survival (CSS) rates, complication rates, perioperative outcomes or quality of life who have undergone ipsilateral adrenalectomy.

3. Lymph Node Dissection (LND)

In patients who are clinically negative for lymph nodes, lymph node dissection (LND) together with partial nephrectomy or radical nephrectomy is still controversial. [18]

The clinical evaluation of the status of the lymph nodes is based on the detection of enlargement of lymph nodes, by either computed tomography (CT)/magnetic resonance imaging (MRI) or intraoperatively palpability of enlarged lymph nodes. However, less than 20% of lymph nodes suspected to be metastasized clinically (cN+), are positive for metastatic disease at histopathological examination (pN+). [19]

Both magnetic resonance imaging (MRI) and computed tomography (CT) are inadequate and inappropriate to detect malignant disease in lymph nodes of normal size and shape. [20]

Some of the retrospective studies indicate that lymphadenectomy may be clinically beneficial and preferable in patients at risk for lymphogenic spread.

In another study, the outcomes of radical nephrectomy with or without lymph node dissection in patients with high-risk non-metastatic renal cell carcinoma (RCC) were compared. As a result of this study, lymph node dissection (LND) was not significantly associated with a reduced risk of cancer-specific mortality, distant metastases or all-cause mortality. Both elective lymph node dissection (eLND) or extended lymph node dissection were not associated with improved clinical oncologic outcomes. [21]

In some studies, the number of lymph node metastases with intra- and extra-capsular extension is associated with clinical prognosis. [22] Patients with less than 4 positive lymph nodes and no extra nodal extension seem to have much better survival outcomes.

a. Outcomes

In a database analysis study with more than 9,000 patients, it was shown that an enlarged lymph node dissection (LND) did not affect disease-specific survival (DSS) in patients with pathologically limited negative nodes. [23] However, in patients with pathologically proven lymphogenic spread (pN+), an increase of ten for the number of dissected nodes caused an absolute increase of 10% in disease-specific survival (DSS).

It was also reported in a large cohort study of 1983 patients by Capitano that extended lymph node dissection (eLND) leads to prolongation of cancer-specific survival (CSS) in patients with unfavorable prognostic features. [24]

According to the databases in the medical literature, regarding the morbidity associated with extended lymph node dissection (eLND), it is not associated with an increased risk of Clavien grade > 3 complications. Furthermore, lymph node dissection was not associated with length of stay or estimated blood loss. [25]

b. Lymph node dissection with surgery

Only one research evaluating the clinical value of lymph node dissection (LND) combined with surgical treatment of primary renal cell carcinoma (RCC) has been published so far. With an incidence of only 4%, the risk of lymphatic spread appears to be very low. Recognising the latter, only a staging effect was attributed to lymph node dissection (LND). [19]

This research included a very high percentage of patients with pT2 tumours, which are not at increased risk for lymph node metastases. Additionally, only 25% of patients with pT3 tumours were subjected to a complete lymph node dissection (LND).

c. Extent of lymph node dissection

The optimal extent of lymph node dissection (LND) remains controversial. Some studies In medical literature suggest that an extended lymph node dissection (eLND) should involve the lymph nodes surrounding the ipsilateral great vessel and the inter-aortocaval region from the crus of the diaphragm to the common iliac artery. [20,26,27][20, 26, 27]

At least fifteen lymph nodes should be removed. [28, 29] Sentinel lymph node dissection (LND) is an investigational technique. [30, 31]

4. Embolisation

No benefit of tumor embolization before routine nephrectomy has been demonstrated. [32]

Embolization in patients which unsuitable for surgery or with non-resectable disease may help to keep symptoms under control. These symptoms include flank pain and invasive hematuria. [33]


References(Show/Hide)

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2. Thompson, R.H., et al. Radical nephrectomy for pT1a renal masses may be associated with decreased overall survival compared with partial nephrectomy. J Urol, 2008. 179: 468.

3. Huang, W.C., et al. Partial nephrectomy versus radical nephrectomy in patients with small renal tumors–is there a difference in mortality and cardiovascular outcomes? J Urol, 2009. 181: 55.

4. Thompson, R.H., et al. Comparison of partial nephrectomy and percutaneous ablation for cT1 renal masses. Eur Urol, 2015. 67: 252.

5. Sun, M., et al. Management of localized kidney cancer: calculating cancer-specific mortality and competing risks of death for surgery and nonsurgical management. Eur Urol, 2014. 65: 235.

6. Kunath, F., et al. Partial nephrectomy versus radical nephrectomy for clinical localised renal masses. Cochrane Database Syst Rev, 2017. 5: CD012045.

7. Sun, M., et al. Comparison of partial vs radical nephrectomy with regard to other-cause mortality in T1 renal cell carcinoma among patients aged >/=75 years with multiple comorbidities. BJU Int, 2013. 111: 67.

8. Shuch, B., et al. Overall survival advantage with partial nephrectomy: a bias of observational data? Cancer, 2013. 119: 2981.

9. Scosyrev, E., et al. Renal function after nephron-sparing surgery versus radical nephrectomy: results from EORTC randomized trial 30904. Eur Urol, 2014. 65: 372.10. Lane, B.R., et al. Survival and Functional Stability in Chronic Kidney Disease Due to Surgical Removal of Nephrons: Importance of the New Baseline Glomerular Filtration Rate. Eur Urol, 2015. 68: 996.

11. Antonelli, A., et al. Elective partial nephrectomy is equivalent to radical nephrectomy in patients with clinical T1 renal cell carcinoma: results of a retrospective, comparative, multi-institutional study. BJU Int, 2012. 109: 1013.

12. Shekarriz, B., et al. Comparison of costs and complications of radical and partial nephrectomy for treatment of localized renal cell carcinoma. Urology, 2002. 59: 211.

13. Van Poppel, H., et al. A prospective randomized EORTC intergroup phase 3 study comparing the complications of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma. Eur Urol, 2007. 51: 1606.

14. Gabr, A.H., et al. Approach and specimen handling do not influence oncological perioperative and long-term outcomes after laparoscopic radical nephrectomy. J Urol, 2009. 182: 874.

15. Janssen, M.W.W., et al. Survival outcomes in patients with large (>/=7cm) clear cell renal cell carcinomas treated with nephron-sparing surgery versus radical nephrectomy: Results of a multicenter cohort with long-term follow-up. PLoS One, 2018. 13: e0196427.

16. Mir, M.C., et al. Partial Nephrectomy Versus Radical Nephrectomy for Clinical T1b and T2 Renal Tumors: A Systematic Review and Meta-analysis of Comparative Studies. Eur Urol, 2017. 71: 606.

17. Lane, B.R., et al. Management of the adrenal gland during partial nephrectomy. J Urol, 2009. 181: 2430.

18. Bekema, H.J., et al. Systematic review of adrenalectomy and lymph node dissection in locally advanced renal cell carcinoma. Eur Urol, 2013. 64: 799.

19. Blom, J.H., 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.

20. Capitanio, U., et al. Lymph node dissection in renal cell carcinoma. Eur Urol, 2011. 60: 1212.

21. Gershman, B., et al. Radical Nephrectomy with or without Lymph Node Dissection for High Risk Nonmetastatic Renal Cell Carcinoma: A Multi-Institutional Analysis. J Urol, 2018. 199: 1143.

22. Kim S, T.H., et al. The relationship of lymph node dissection with recurrence and survival for patients treated with nephrectomy for high-risk renal cell carcinoma. J Urol, 2012. 187: e233.

23. Whitson, J.M., et al. Population-based comparative effectiveness of nephron-sparing surgery vs ablation for small renal masses. BJU Int, 2012. 110: 1438.

24. Capitanio, U., et al. Extent of lymph node dissection at nephrectomy affects cancer-specific survival and metastatic progression in specific sub-categories of patients with renal cell carcinoma (RCC). BJU Int, 2014. 114: 210.

25. Gershman, B., et al. Perioperative Morbidity of Lymph Node Dissection for Renal Cell Carcinoma: A Propensity Score-based Analysis. Eur Urol, 2018. 73: 469.

26. Herrlinger, A., et al. What are the benefits of extended dissection of the regional renal lymph nodes in the therapy of renal cell carcinoma. J Urol, 1991. 146: 1224.27. Chapin, B.F., et al. The role of lymph node dissection in renal cell carcinoma. Int J Clin Oncol, 2011. 16: 186.

28. Capitanio, U., et al. Extent of lymph node dissection at nephrectomy affects cancer-specific survival and metastatic progression in specific sub-categories of patients with renal cell carcinoma (RCC). BJU Int, 2014. 114: 210.

29. Kwon, T., et al. Reassessment of renal cell carcinoma lymph node staging: analysis of patterns of progression. Urology, 2011. 77: 373.

30. Bex, A., et al. Intraoperative sentinel node identification and sampling in clinically node-negative renal cell carcinoma: initial experience in 20 patients. World J Urol, 2011. 29: 793.

31. Sherif, A.M., et al. Sentinel node detection in renal cell carcinoma. A feasibility study for detection of tumour-draining lymph nodes. BJU Int, 2012. 109: 1134.

32. May, M., et al. Pre-operative renal arterial embolisation does not provide survival benefit in patients with radical nephrectomy for renal cell carcinoma. Br J Radiol, 2009. 82: 724.

33. Maxwell, N.J., et al. Renal artery embolisation in the palliative treatment of renal carcinoma. Br J Radiol, 2007. 80: 96.

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