Advances in kidney cancer

Advances in kidney cancer

Dr. Shailesh Satpute | Northside Hospital Cancer Institute

March marks Kidney Cancer Awareness Month. Renal cell carcinoma (RCC) ranks as the third most common urologic malignancy. In 2025, it’s estimated that there will be 80,980 new cases and 14,510 deaths from RCC in the U.S.1?

Only 9% of patients exhibit the classic triad of symptoms: hematuria, abdominal pain and a palpable mass. In recent years, there has been an increase in diagnoses of stage 1 RCC and a decrease in stage 4 disease, largely due to the frequent use of imaging studies leading to incidental findings.?

Early-stage RCC

For small renal tumors that can be removed, needle biopsies before surgery should be avoided. Kidney-sparing approaches like partial nephrectomy (kidney removal) are preferred when possible. For tumors under 3 cm, less invasive techniques like cryotherapy or radiofrequency ablation are recommended. In elderly patients with other health issues, active surveillance is appropriate for small tumors. For complex tumors or those involving vascular structures, radical nephrectomy is required.

The use of adjuvant (postoperative) therapy in renal cell carcinoma was debated until recently because past trials with targeted drugs didn't show clear benefits.?

  • One study called?S-TRAC?was the only positive trial that showed improved progression-free survival with sunitinib, a VEGF receptor tyrosine kinase inhibitor (TKI), administered for one year after nephrectomy.^2
  • In another trial?KEYNOTE-564, pembrolizumab was given for one-year post-surgery to patients with intermediate to high risk of recurrence. These patients showed improved progression-free survival^3?as well as overall survival.^4 This trial has set a new standard of care for adjuvant use of pembrolizumab in resected RCC.

Metastatic RCC

With modern drugs like VEGF-TKIs and immune checkpoint inhibitors, cytoreductive nephrectomy is no longer appropriate for all patients with metastatic RCC.

A recent trial called?CARMENA?showed that for patients with intermediate to poor-risk disease, taking sunitinib without surgery was as good for overall survival as having surgery first followed by sunitinib.^5?But surgery is still appropriate for patients with low-risk, low-volume disease.?

Many combination therapies have been approved in front-line treatment of metastatic RCC. Nivolumab (PDL1 inhibitor) with ipilimumab (CTLA4 inhibitor) demonstrated better overall survival than sunitinib in patients with intermediate or poor-risk metastatic RCC.^6?Since 2019, four combinations of VEGF TKI and PD-1/PD-L1 inhibitors have been approved: axitinib + pembrolizumab, axitinib + avelumab, carbozantinib + nivolumab and lenvatinib + pembrolizumab. These regimens have comparable overall survival and response rates, but they can cause side effects like hypertension, diarrhea, fatigue and hypothyroidism.?

In the second/third-line treatment, axitinib, cabozantinib, lenvatinib, sorafenib and tivozanib are approved. Studies have shown that patients previously treated with VEGF TKI may still respond to a different VEGF-targeted therapy. A recent trial tested a novel HIF-2α inhibitor belzutifan in metastatic RCC patients previously treated with VEGF and immune checkpoint inhibitor therapies. Compared to everolimus, belzutifan showed better progression-free survival and response rates and fewer side effects, leading to its FDA approval.^7

Novel strategies to combine these agents as well as developing novel approaches such CAR-T therapy are being actively investigated. Patients that have oligometastatic progression, metastatectomy or radiation therapy remain viable options. Other treatments like bone-targeting therapies, nutrition support and palliative care have helped improve patients’ quality of life.

Conclusion:?The evolution of RCC management continues as we learn more about tumor biology, discover new therapeutic agents and rethink old treatment methods in the context of new and improved systemic therapies. Participating in clinical trials remains important for the development of new treatments and improving patient care.


Learn more about kidney cancer treatment at Northside.


References:

  1. Siegel, Rachel L., et al. "Cancer Statistics, 2025."?CA: A Cancer Journal for Clinicians?75, no. 1 (January-February 2025): 10-45.?https://doi.org/10.3322/caac.21871. Epub January 16, 2025.
  2. Ravaud, A., et al. "Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy."?The New England Journal of Medicine?375, no. 23 (December 8, 2016): 2246-2254.?https://doi.org/10.1056/NEJMoa1611406. Epub October 9, 2016.
  3. Choueiri, T. K., et al. "Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma."?The New England Journal of Medicine?373, no. 19 (November 5, 2015): 1814-1823.?https://doi.org/10.1056/NEJMoa1510016. Epub September 25, 2015.
  4. Choueiri, T. K., P. Tomczak, S. H. Park, et al. "Overall Survival Results from the Phase 3 KEYNOTE-564 Study of Adjuvant Pembrolizumab versus Placebo for the Treatment of Clear Cell Renal Cell Carcinoma (ccRCC)."?Journal of Clinical Oncology?42, no. suppl 4 (2024): LBA359.
  5. Méjean, A., et al. "Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma."?The New England Journal of Medicine?379, no. 5 (August 2, 2018): 417-427.?https://doi.org/10.1056/NEJMoa1803675. Epub June 3, 2018.
  6. Motzer, R. J., et al. "Nivolumab Plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma."?The New England Journal of Medicine?378, no. 14 (April 5, 2018): 1277-1290.?https://doi.org/10.1056/NEJMoa1712126. Epub March 21, 2018.
  7. Choueiri, T. K., et al. "Belzutifan versus Everolimus for Advanced Renal-Cell Carcinoma."?The New England Journal of Medicine?391 (August 21, 2024): 710-722.?https://doi.org/10.1056/NEJMoa2313906.


Dr. Shailesh Satpute has several years of experience in cancer care, teaching research and clinical trials.? With each passing year, he sees cancer outcomes improving and feels proud to be part of that legacy. His special interests include gastrointestinal, lung, kidney, bladder and testicular cancers.?


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