Renal cell carcinoma (RCC) represents 90% of all kidney cancers, with most patients being diagnosed with clear cell histology.1 Metastatic renal cell carcinoma (mRCC) is not uncommon; 35% of patients eventually developing metastases and more than 25% of patients are diagnosed with metastatic disease upon initial diagnosis.2 Although treatments vary on a patient-to-patient basis, options include systemic and hormonal therapy, radiation, and surgery.3

Systemic treatments include immune checkpoint inhibitors (ICIs): programmed cell death 1 (PD-1) inhibitors and programmed cell death ligand 1 (PD-L1) inhibitors, and anticytotoxic T lymphocyte protein 4 (CTLA-4) antibodies.3 In addition to ICIs, there are also vascular endothelial growth factor (VEGF) inhibitors, tyrosine kinase inhibitors (TKIs), and mammalian target of rapamycin (mTOR) inhibitors.3 Despite the array of medications available, these treatment options typically do not result in a complete response in patients with mRCC.3 Therefore, these patients are frequently evaluated for surgery, both of the primary tumor and metastases.

The decision to pursue metastasectomy can be challenging, especially in the setting of increasingly available and innovative systemic options. However, there is evidence to support the role of metastasectomy in providing patients with mRCC an improvement in certain clinical outcomes such as median cancer-specific survival (CSS) and overall survival (OS).4,5 Prior studies have indicated that if metastasectomy is pursued, there are certain clinical features that appear to make metastasectomy more favorable: younger age at presentation, solitary metastasis, lung metastasis, and metachronous presentation with disease-free survival (DFS) greater than 12 months.6,7

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Much of the data from previous studies evaluating metastasectomy in mRCC occurred prior to the significant expansion of systemic treatment options such as TKIs and ICIs. Therefore, a group led by Dragomir et al recently aimed to update the outcomes associated with metastasectomy in the current treatment environment of mRCC, and published their findings in Urologic Oncology.1

Between January 2011 and April 2019, the authors evaluated patients with mRCC who underwent complete metastasectomy (CM) and compared them to control patients who did not using the Canadian Kidney Cancer information system (CKCis) database.

The cohort included a total of 1471 patients with mRCC who had undergone a prior nephrectomy, of which 250 (17%) underwent CM compared with 1221 (83%) without a metastasectomy. The CM group had a significantly longer median time between primary RCC tumor and diagnosis of metastasis compared with the control group (17.9 months vs 4.8 months, P <.001). This corresponded to 55.6% of CM and 33.3% of control patients having had an interval of longer than 1 year from primary RCC diagnosis to their first metastasis. The most common sites of CM included the lung (29.4%), adrenals (15.2%), and lymph nodes (12.4%).

Locations of the actual metastases varied between the groups, with the CM group having more patients with adrenal metastases compared with the control group (16% vs 10.1%, respectively, P =.0065) and more patients in the CM group with brain metastases compared with the control group (8.8% vs 1.5%, respectively, P <.0001).

More individuals in the CM group than in the control group had lung (54.2% vs 37.2%, P <.0001), bone (15.7% vs 10.8%, P <.046), and liver (9.8% vs 3.6%, P <.0017) metastases, respectively.

Plus, 73.5% of patients in the control arm received a targeted systemic treatment during their follow-up compared with only 47.4% in the CM group (P <.0001). Patients more likely to undergo a CM included those younger than 65 years, metastasis in only 1 location, and metachronous disease, which is consistent with prior studies, as mentioned previously.

In a matched cohort analysis, the authors matched 229 patients undergoing CM to 803 patients not treated with a CM (the control group). Median OS was significantly better in the CM group (81 months) compared with the control group (61 months, P <.001). There was a higher proportion of patients alive after 12 months in the CM group (96%) compared with matched controls (89.8%). There was also a higher 5-year OS in the CM group (63.2%) compared with the matched control group (51.4%, P <.001).

A multivariate analysis found that patients undergoing CM had a lower risk of mortality compared with those who did not undergo CM (hazard ratio [HR], 0.41; 95% CI, 0.27-0.63). More than 1 site of metastasis was associated with an increased risk of death (HR, 3.64, 95% CI, 1.46-9.07).

The authors concluded that when compared with patients who did not undergo CM, those with CM had longer OS and longer time before starting systemic therapy. Therefore, the authors suggest that patients with mRCC should be strongly considered for CM. This study was limited by the inclusion of only Canadian patients, and the fact that it was an observational study, which could predispose the study to selection bias. 

This study has similar findings to a prior study conducted by Alt et al that evaluated a total of 887 patients with mRCC, of which 125 (14%) underwent CM.4 The authors did, however, group those patients who had incomplete metastasectomy with those not undergoing any type of metastasectomy. CM was associated with a significant increase in median CSS (4.8 years vs 1.3 years, P <.001). In addition, lack of CM was associated with an increased risk of death from RCC (HR, 2.91; 95% CI, 2.17-3.90, P <.001).

In patients with multiple non–lung-only metastases who underwent CM, there was a survival advantage with a 5-year CSS rate of 32.5% compared with 12.4% without complete resection (P <.001). Even patients with 3 or more metastatic lesions had improved CSS with CM. There was a significant benefit in 5-year CSS rates in those patients with only-lung metastases, where CM resulted in a 5-year CSS of 73.6% compared with 19% in those who did not undergo complete resection (P <.001).

The current study published by Dragomir et al does appear to provide similar results to prior studies. In appropriate patients with mRCC, CM should be strongly considered, especially in those patients younger than 65 years, those who have a single metastasis, and in those who have metastasis in the lung, specifically. CM has shown to improve clinical outcomes while delaying the need to initiate systemic therapy. The latter could have a significant impact on a patient’s quality of life, as well as on the overall health care costs associated with systemic therapy. Future studies may aim to focus on these factors in patients undergoing CM.

References

  1. Dragomir A, Nazha S, Wood LA, Rendon RA, Finelli A, Hansen A, et al. Outcomes of complete metastasectomy in metastatic renal cell carcinoma patients: The Canadian Kidney Cancer information system experience. Urol Oncol. 2020;S1078-1439(20)30342-2. doi:10.1016/j.urolonc.2020.07.021.
  2. Flanigan RC, Campbell SC, Clark JI, Picken MM. Metastatic renal cell carcinoma. Curr Treat Options Oncol. 2003;4(5):385–390. doi:10.1007/s11864-003-0039-2
  3. Bamias A, Escudier B, Sternberg CN, Zagouri F, Dellis A, Djavan B, et al. Current clinical practice guidelines for the treatment of renal cell carcinoma: a systematic review and critical evaluation. Oncologist. 2017;22(6):667-679. doi:10.1634/theoncologist.2016-0435
  4. Alt AL, Boorjian SA, Lohse CM, Costello BA, Leibovich BC, Blute ML. Survival after complete surgical resection of multiple metastases from renal cell carcinoma. Cancer. 2011;117(13):2873–2882. doi:10.1002/cncr.25836
  5. Kwak C, Park YH, Jeong CW, Lee SE, Ku JH. Metastasectomy without systemic therapy in metastatic renal cell carcinoma: comparison with conservative treatment. Urol Int. 2007;79(2):145-151. doi:10.1159/000106329
  6. Kavolius JP, Mastorakos DP, Pavlovich C, Russo P, Burt ME, Brady MS. Resection of metastatic renal cell carcinoma. J Clin Oncol. 1998;16(6):2261-2266. doi:10.1200/JCO.1998.16.6.2261
  7. Tosco L, Van Poppel H, Frea B, Gregoraci G, Joniau S. Survival and impact of clinical prognostic factors in surgically treated metastatic renal cell carcinoma. Eur Urol. 2013;63(4):646-652. doi:10.1016/j.eururo.2012.09.037

This article originally appeared on Cancer Therapy Advisor

Topics:

Kidney Cancer Renal Cell Carcinoma