Editing Metastatic Kidney Cancer (section)

==== Targeted Therapy ====
*'''The introduction of effective targeted therapy questioned the role of CN in the modern era'''

===== CN followed by Targeted Therapy vs. Targeted Therapy alone =====

====== <span style="color:#ff00ff">CARMENA</span> (Clinical Trial to Assess the Importance of Nephrectomy) ======
* '''Population: 452 patients with metastatic ccRCC'''
** 44% had poor-risk disease, 56% had intermediate-risk
*** '''Trial does not apply to patients with favourable-risk'''
* '''<span style="color:#ff0000">Randomized to CN followed by sunitnib vs. sunitnib alone'''
* '''Primary outcome: OS'''
* '''Median follow-up 50.2 months'''
* '''<span style="color:#ff0000">Results'''
** '''<span style="color:#ff0000">OS: sunitinib alone was non-inferior to CN followed by sunitinib</span>''' (HR 0.89; 95% CI 0.71–1.10)
** '''No significant difference PFS or response to treatment'''
* [https://pubmed.ncbi.nlm.nih.gov/29860937/ Méjean, Arnaud, et al. "Sunitinib alone or after nephrectomy in metastatic renal-cell carcinoma." New England Journal of Medicine 379.5 (2018): 417-427.]

===== CN before vs. after Targeted Therapy =====

* In patients with mRCC who are being considered for CN, the optimal timing relative to the initiation of systemic therapy also remains controversial.

* '''Advantages of initiating systemic therapy prior to CN:'''
*# '''May provide symptomatic control and disease stabilization or regression for patients with a large tumour burden'''
*# '''May allow the identification of patients not likely to benefit from CN; specifically, patients who progress rapidly on systemic therapy have a poor prognosis and are unlikely to derive a survival advantage by undergoing CN'''
*# '''Decreases the size of the primary tumour in a proportion of patients'''
*#* The median decrease in size is estimated to be 7-32% and the clinical impact of this is questionable
*#* Tumour may also increase in size or complexity during systemic therapy, reducing the feasibility of resection
* '''Advantages of upfront CN (3):'''
*# '''Palliating symptoms related to the primary tumour'''
*# '''Eliminating a source of secondary metastases'''
*# '''Improving host immune dysfunction'''

====== <span style="color:#ff00ff">SURTIME ======
* '''Population: 99 patients with metastatic ccRCC'''
* '''<span style="color:#ff0000">Randomized to upfront CN followed by sunitnib vs. upfront sunitinib followed by CN (deferred CN)'''
** '''Investigated optimal timing of CN relative to initiation of systemic therapy'''
* '''Primary endpoint: disease progression at 28 weeks'''
* '''<span style="color:#ff0000">Results:'''
** '''<span style="color:#ff0000">No difference in disease progression</span>''' (42.0% vs. 42.9%, respectively at 28 weeks of follow-up; p>0.99) '''between upfront vs. deferred CN'''
** '''OS improved in deferred CN group (median OS 32.4 vs. 15 months; p=0.034)'''
*** '''Difficult to interpret this result due to discordance with the disease progression results'''
* [https://pubmed.ncbi.nlm.nih.gov/30543350/ Bex, Axel, et al. "Comparison of immediate vs deferred cytoreductive nephrectomy in patients with synchronous metastatic renal cell carcinoma receiving sunitinib: the SURTIME randomized clinical trial." JAMA oncology 5.2 (2019): 164-170.]