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Deferred surgery for kidney cancer: A viable option in the age of improved systemic therapies?

Newer targeted therapies and immunotherapies approved over the last decade can effectively manage metastatic kidney cancer on their own. This has led to a debate about whether cytoreductive nephropathy is still necessary or if systemic therapy alone is an adequate initial treatment.

 

A recent meta-analysis reviewing 9 studies with over 3000 metastatic kidney cancer patients tried to provide more clarity on this topic.

 

Kidney cancer – A silent disease


Kidney cancer (also called renal cancer) is a disease that results from the uncontrolled growth of cells in the kidney. It is the 14th most common cancer worldwide [1]. The average age of kidney cancer diagnosis is 64 years [2]. It is quite rare in individuals under the age of 45 years.


Kidney cancer surgery

Kidney cancer does not show any symptoms in the early stage. With time, kidney cancer progresses to the aggressive stage which manifests symptoms. Common symptoms are blood in the urine, pain in the back, unexpected weight loss, and loss of appetite. When the cancer has spread to other parts of the body, it is called metastatic kidney cancer.

 

A paradigm shift in the treatment of metastatic kidney cancer


The surgical removal of cancer-containing kidney is called cytoreductive nephrectomy. It is usually followed by systemic therapy which uses various types of medications, such as immunotherapy and targeted therapy, to kill the cancer cells.

 

This approach in which cancer is surgically removed before starting systemic therapy is known as upfront cytoreductive nephrectomy. The alternate would be giving the systemic therapy before surgery and the therapy would be called deferred cytoreductive nephrectomy.

 

Upfront cytoreductive nephrectomy has traditionally been the standard of care for metastatic kidney cancer. However, the emergence of novel targeted therapy and immunotherapy agents has tipped the balance in favor of earlier systemic therapy [3]. They have improved outcomes significantly compared to older cytokine immunotherapies.

 

Consequently, there has been renewed debate around the need and timing of cytoreductive nephrectomy in metastatic kidney cancer.

 

Deferred cytoreductive nephrectomy: What's the rationale?


Deferring (or delaying) cytoreductive nephrectomy has several potential advantages:

 

  • Systemic therapy can shrink tumors first, allowing better surgery results later.

  • It can identify patients unlikely to benefit from cytoreductive nephrectomy due to aggressive disease.

  • Avoiding complications from upfront surgery may enable more patients to receive subsequent therapy.

  • Delayed cytoreductive nephrectomy may improve the quality of life in some patients.

 

However, there is limited data from clinical studies to recommend deferred cytoreductive nephrectomy as a routine practice.

 

A meta-analysis (analysis of various individual clinical studies) aimed to provide clarity [4]. It analyzed the available evidence on outcomes based on cytoreductive nephrectomy timing.

 

Overview of meta-analysis methods


The researchers systematically searched major medical databases for relevant studies published until April 2022 comparing upfront and deferred cytoreductive nephrectomy with systemic therapy for metastatic kidney cancer.

 

Nine retrospective studies involving 3157 patients met the criteria for inclusion. The primary outcome was overall survival. The researchers compared the relative survival benefit of deferred cytoreductive nephrectomy versus upfront cytoreductive nephrectomy.

 

Deferred cytoreductive nephrectomy improves overall survival


In the pooled analysis, undergoing cytoreductive nephrectomy after systemic therapy was associated with significantly better overall survival than upfront cytoreductive nephrectomy.

 

Deferred cytoreductive nephrectomy delayed disease progression based on radiographic assessment and reduced the risk of death by 29%. The survival advantage was consistent across most subgroup analyses based on the sample size, age, gender, and disease risk status.

 

Notably, there was no difference between groups when immunotherapy-based combinations were used as systemic therapy. Targeted therapy combinations showed the largest benefit from deferred cytoreductive nephrectomy.

 

Limitations to consider


Although promising, there are important limitations when interpreting these findings:

 

  • All were retrospective analyses prone to biases in patient selection and data collection.

  • The studies had relatively small sample sizes and short follow-ups.

  • Details on systemic therapy duration and timing of deferred cytoreductive nephrectomy were lacking.

  • Adverse events and quality of life impact could not be assessed.

  • Groups may not have been balanced for disease characteristics.

 

Ongoing randomized trials will provide higher-quality evidence on the risks and benefits of deferred cytoreductive nephrectomy.

 

Key takeaways


  • Delaying cytoreductive nephrectomy after systemic therapy may improve overall survival compared to upfront cytoreductive nephrectomy.

  • These results do not mean delayed cytoreductive nephrectomy is appropriate for all patients.

  • Currently underway large randomized clinical trials will validate these findings.


References


1. “Kidney cancer statistics | World Cancer Research Fund International,” WCRF International. Accessed: Nov. 17, 2023.

2. “Key Statistics About Kidney Cancer.” Accessed: Nov. 17, 2023.

3. C. Van Praet et al., “Current role of cytoreductive nephrectomy in metastatic renal cell carcinoma,” Turk J Urol, vol. 47, no. Suppl 1, pp. S79–S84, Feb. 2021, doi: 10.5152/tud.2021.21006.

4. K.-P. Li et al., “Comparison of upfront versus deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma receiving systemic therapy: a systematic review and meta-analysis,” Int J Surg, vol. 109, no. 10, pp. 3178–3188, Oct. 2023, doi: 10.1097/JS9.0000000000000591.

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