Better Practice: No More Surgery for Stage 4 Kidney Cancer?!

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ASCO Immediate Release; Carmena trial

Introduction

The summary for the above Carmena trial; randomised phase III clinical trial to study if patients with advanced kidney cancer can avoid surgery altogether without compromising survival.

  • Current standard of care: nephrectomy for patients with kidney cancer who have metastatic disease when the cancer is first diagnosed, followed by targeted therapy; affecting 20% of patients (huge numbers!)
  • Results: median/ average overall survival for people who received only the targeted therapy (TT alone) sunitinib was 18.4 months, compared to 13.9 months for those who received surgery followed by sunitinib (surgery + TT), the current standard of care.
  • Conclusions: Sunitinib alone is not inferior to surgery (nephrectomy) followed by sunitinib in synchronous mRCC both in intermediate and poor MSKCC risk groups. Surgery should not be anymore the standard of care when medical treatment is required.
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MSKCC risk groups

Previous standard of care (upfront nephrectomy followed by systemic therapy) is the results from South West Oncology Group (Flanigan RC, 2001) and other research centre which showed better survival.

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Median/ average survival was 11.1months (nephrectomy + interferon)  vs 8.1 months (interferon alone), before the availability of targeted therapy in 2001.

Patients selection

With proven efficacy/ effectiveness of systemic treatment (targeted therapy) and proven non-inferiority of targeted therapy alone (Carmena trial) above, is nephrectomy still beneficial?

Yes, to selected few patients.

Those patients who might benefit from upfront surgery are patients with:

  • Lung metastasis, which is the most common site of metastasis
    • Solitary or low metastatic volume,
    • High survival rate with resection of pulmonary metastasis (5-year survival rate 36% – 54%,  curative in 1/3 of patients)
    • Safe
  • Ability to resect completely primary kidney cancer and the metastasis
    • Complete resection of metastases was associated with a twofold decreased risk of death from RCC, 5 year survival rate about 35% – 60%.
  • Good performance status
  • More than 1 year from disease free to first metastasis
  • Favourable MSKCC risk group (none of risk factor)
  • No liver or brain metastasis
  • Patients with intractable pain, massive bleeding, uncontrolled hypertension, poorly controlled symptoms due to paraneoplastic syndromes.
    • The effectiveness in palliating the above is not certain.

With the latest results from Carmena trial, a more exhaustive multidiscipline discussions need to be conducted to discuss each cases before upfront nephrectomy in Stage 4 kidney cancer.

This is to avoid unnecessary surgery (nephrectomy, metastasectomy) and it’s accompanying side effects.

Surgery risks; blood loss, infection, pulmonary embolism, heart problems, general anesthesia risk, death (6-11%). Also, delays targeted therapy for patients while waiting recovery from surgery and cancer worsens rapidly during this delay.

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