📃 Paper Title: Comparison of Immediate vs Deferred Cytoreductive Nephrectomy in Patients With Synchronous Metastatic Renal Cell Carcinoma Receiving Sunitinib: The SURTIME Randomized Clinical Trial
🧍 Author: Bex
🕒 Year: 2018
📚 Journal: JAMA Oncology
🌎 Country: The Netherlands
ㅤContext to the study:
Can you tell me about the evidence for or against cytoreductive nephrectomy and the timing of it in the current era of systemic treatments?
ㅤ✅ Take-home message of study:
Pretreatment with Sunitinib prior to cytoreductive nephrectomy does not improve 28 week progression free survival compared to up-front nephrectomy followed by Sunitinib (but seems non-inferior).
Using Sunitinib first does seem to increase the number of patients who receive systemic treatment (98% vs 80% here) and may serve to select patients most likely to benefit from CNx (by avoiding nephrectomy in those with progressive, treatment-resistant disease)
Overall survival appeared higher in Sunitinib-first arm but underpowered for statistical significance
Surgical complications were broadly similar (~50%) between arms
ㅤ Multicentre Randomised Clinical Trial without blinding. Enrolment 2010 continued to 2016.
Randomisation in 1:1 ratio to:
▪ Immediate cytoreductive nephrectomy followed by Sunitinib
▪ Sunitinib (3 cycles) followed by cytoreductive nephrectomy
ㅤ
Study participants:
99 patients (80 male, 19 female) from 19 centres across 4 countries (Netherlands, Belgium, UK, Canada)
Inclusion
Disease: Metastatic clear cell renal cell carcinoma, never previously treated*, with a resectable and asymptomatic primary tumour. No CNS involvement. Ultimately 88% were MSKCC intermediate risk.
Patient: WHO Performance status of 0, adequate bone marrow, renal, liver and cardiac function and ≤ 3 surgical risk factors (based on Culp et al. selection for CNx including cT3 or greater disease, liver mets,
retroperitoneal or supradiaphragmatic LNs, albumin and LDH
measures)
*prior radiotherapy for bone metastases was allowed
ㅤ
ㅤ
Key study outcomes:
▪ Median follow-up 3.3 years
▪ Primary Outcome (revised) 28 week progression-free rate on intention-to-treat analysis. This was 42% in the immediate CNx arm and 43% in the deferred CNx arm (p=0.61).
▪ Sunitinib was received by 80% of patients in immediate CNx arm but 98% in Sunitinib-first arm
▪ 14 patients (28%) randomised to deferred CNx arm ultimately were recommended against nephrectomy
▪ Overall survival was 15 months in immediate CNx arm and 32.4 months in deferred CNx arm, but without statistical significance
ㅤ
ㅤ
Study Limitations:
Poor accrual and relatively high drop-out each arm. Target enrolment was 458 patients to assess progression-free survival; however only 99 patients randomised and took 5.7 years to recruit (73 in per protocol analysis). Primary outcome changed on this basis. Relatively strict inclusion criteria - generalisability to many patients is questionable. Few female patients represented. Non-Sunitinib immunotherapy may perform differently. Like CARMENA, favourable risk patients are under-represented.
ㅤ