Kidney Cancer Treatment by Stage

NCI's PDQ summary for health professionals says the renal cell staging system is built on one thing: how far the tumor has spread beyond the kidney. The AJCC tables it reprints turn that into numbers.

Stage I is a tumor 7 cm or smaller that stays inside the kidney. It splits at 4 cm. T1a is at or below that mark, T1b above it. Stage II is a tumor larger than 7 cm, still inside the kidney. It splits again at 10 cm. Stage III adds involved regional lymph nodes, or growth into major veins. Stage IV is the most advanced group.

Two cautions in PDQ are worth knowing. Blood vessel involvement may not be a bad sign, so long as the tumor is otherwise confined to the kidney. And odd liver blood tests can come from a paraneoplastic syndrome. That is a body-wide reaction to the tumor. PDQ says it reverses when the tumor comes out, and does not always mean spread.

PDQ also states that CT is as good as or better than MRI for finding kidney masses, except when the CT is unclear or iodine contrast cannot be used.

American Cancer Society projections for the United States in 2026, published on SEER Stat Facts, come to 80,450 new cases of kidney and renal pelvis cancer and 15,160 deaths. NCI's own SEER measurement, covering people diagnosed from 2016 through 2022, puts 5-year relative survival at 79.2% overall and 93.6% when the tumor is still confined to the kidney — and two thirds of cases are found at that localized stage.

About 85% of renal cell cancers are adenocarcinomas, mostly arising from the proximal tubule. Most of the rest are transitional cell carcinomas of the renal pelvis, which PDQ handles in a separate summary. Adenocarcinomas divide into clear cell and granular cell types, and both can appear in one tumor.

One PDQ line argues against judging by size alone: spread has been documented from lesions as small as 0.5 cm.

PDQ says current treatment cures more than half of stage I renal cell cancers. Its option list is long.

• Partial nephrectomy, in selected patients.
• Radical nephrectomy.
• Simple nephrectomy.
• Cryotherapy.
• Thermal ablation.
• Stereotactic ablative body radiation.
• External-beam radiation, for symptom relief.
• Arterial embolization, for symptom relief.
• Clinical trials.

Surgery is the accepted, often curative choice. In well-chosen patients, PDQ says partial nephrectomy matches radical nephrectomy on cancer outcomes. It also preserves more kidney function. Some studies link it to lower mortality.

Radical nephrectomy is a bigger operation than the name suggests. PDQ defines it as removing four things: the kidney, the adrenal gland, the fat around the kidney, and Gerota's fascia. Regional lymph nodes may or may not come out with them. PDQ prefers it when the tumor reaches the inferior vena cava, the large vein that returns blood to the heart.

For people who cannot have surgery, PDQ names cryoablation, thermal ablation, and stereotactic radiation as curative alternatives. When those are out too, external-beam radiation or arterial embolization can relieve symptoms.

Stage II options mirror stage I, minus the ablation entries.

• Partial nephrectomy, in selected patients.
• Radical nephrectomy.
• Radical nephrectomy, then adjuvant pembrolizumab, for high-risk patients.
• Nephrectomy before or after external-beam radiation, in selected patients.
• External-beam radiation, for symptom relief.
• Arterial embolization, for symptom relief.
• Clinical trials.

The new element is the drug after surgery. PDQ, as revised in May 2025, states that pembrolizumab prolonged disease-free survival but not overall survival in high-risk pT2 tumors; longer follow-up published in 2024 has since reported a survival gain as well, so ask which analysis your team is using.

PDQ describes KEYNOTE-564 in detail, and the details matter.

The trial enrolled 994 people with clear cell kidney cancer at high risk of return after surgery. Four groups qualified. Stage II with nuclear grade 4 or sarcomatoid features. Stage III or higher. Regional node spread. Or M1 disease with no cancer left after removal. One group got about a year of pembrolizumab by vein. The rest got placebo. The exact strength and interval belong in the prescribing information and in your own written plan.

At a median 24 months of follow-up, 2-year disease-free survival was 77.3% with pembrolizumab and 68.1% with placebo. The hazard ratio was 0.68, with a 95% confidence interval of 0.53 to 0.87. A later report at 30 months showed 75.2% versus 65.5%.

The cost side is just as specific. Grade 3 or higher side effects hit 32% of the drug group. Serious adverse events hit 20%. Diarrhea and raised liver enzymes led the high-grade list, each at 2%. Adrenal insufficiency, colitis, and diabetic ketoacidosis led the serious list, each at 1%.

PDQ does not present this as settled. As revised in May 2025 it reports that overall survival remains a secondary endpoint awaiting longer follow-up, and that questions have been raised about confounding in the trial.

That caveat has been partly overtaken. The trial's third planned survival analysis, published in the New England Journal of Medicine in 2024 at a median 57.2 months of follow-up, found a significant overall-survival advantage: hazard ratio for death 0.62 (95% CI 0.44 to 0.87, P = 0.005), with estimated 4-year survival of 91.2% against 86.0%. Both readings are worth raising, because whether the benefit outweighs a lasting risk of immune side effects still depends on your own recurrence risk and health.

For stage III, PDQ lists these.

• Radical nephrectomy.
• Embolization first, then radical nephrectomy.
• Radical nephrectomy, then adjuvant pembrolizumab or sunitinib.
• External-beam radiation, for symptom relief.
• Tumor embolization, for symptom relief.
• Nephrectomy, for symptom relief.
• Radiation before or after radical nephrectomy.
• Trials of adjuvant interferon alfa.

PDQ is direct about the evidence, and on one point it is now behind the literature. Its stage III section says no adjuvant trial has shown any effect on overall survival, and that two drugs are linked to longer relapse-free survival.

That first sentence was true when it was written. A 2024 analysis of KEYNOTE-564, at a median follow-up of 57 months, reported a significant overall-survival benefit for adjuvant pembrolizumab across the whole trial population — hazard ratio 0.62, and 91.2% alive at four years against 86.0% on placebo. Most people in that trial had stage III disease. PDQ, as revised in May 2025, has not incorporated that analysis, and it still raises the confounding questions described in the stage II section above.

Both of those things are worth carrying into a conversation with your oncologist: there is now survival evidence, and there are still researchers who think the early data were read too generously. Ask which one your team is working from.

PDQ also notes that lymph node removal is common here, but its value has not been definitively proven.

PDQ groups advanced disease by treatment line rather than by biomarker.

First-line options run as follows.

• Ipilimumab plus nivolumab, for intermediate or poor risk.
• Pembrolizumab plus axitinib.
• Pembrolizumab plus lenvatinib.
• Nivolumab plus cabozantinib.
• Avelumab plus axitinib.
• Cabozantinib alone, for intermediate or poor risk.
• Sunitinib.
• Interferon alfa.
• Interleukin-2.
• Radiation, for symptom relief.

Surgery still appears in that list. Radical nephrectomy is there for T4, M0 tumors. Cytoreductive nephrectomy is there for good-risk M1 disease.

Second-line options are nivolumab, lenvatinib with everolimus, cabozantinib, belzutifan, and radiation for symptoms. PDQ ties most of these to which drugs came first.

Third- and fourth-line options add tivozanib, pazopanib, sorafenib, temsirolimus, axitinib, and everolimus. Bevacizumab is listed too, with or without interferon alfa.

PDQ reports trial numbers for the ipilimumab and nivolumab pair. It enrolled 1,096 patients, 847 of them at intermediate or poor risk. The 18-month survival rate was 75%, against 60% with sunitinib. Response rate was 42% against 27%. Time before growth was not significantly different: 11.6 months against 8.4.

PDQ is plain about the outlook: almost all patients with stage IV renal cell cancer have incurable disease. It adds that carefully selected people may benefit from surgery on a single metastasis, especially after a long disease-free interval.

This summary sorts advanced disease by "intermediate or poor risk." It does not print the criteria behind those labels. It also names no universal biomarker test for kidney cancer. So asking which risk system a team uses is a fair question, not a technicality.

Staging vocabulary in general is covered in cancer staging. The disease itself is described in kidney cancer. The distinction between the two main drug families above is drawn in immunotherapy vs. targeted therapy.

• Call 911 or go to an emergency department if you have a seizure, or sudden confusion, or a headache that comes on hard and fast. NCI lists headache, seizures and dizziness as signs that cancer has spread to the brain.
• Call 911 or go to an emergency department if you become suddenly breathless or have chest pain.
• Call your care team the same day if you run a temperature of 100.4°F (38°C) or higher, or start shaking with chills. Soon after kidney surgery this can point to a wound or urinary infection; on immunotherapy or a targeted drug it can be infection or inflammation the treatment has caused, and the two are told apart by tests, not at home.
• Call your care team the same day if you pass visible blood in your urine, or your side pain gets worse and stays. Those are the same signs NCI lists for renal cell cancer itself.
• Call your care team the same day if you are on an immune checkpoint drug and have diarrhea that is much more frequent than usual, or yellowing of the eyes or skin. NCI lists diarrhea and inflammation of organs among the effects of these drugs.
• Call your care team within a day or two if you have new bone pain that wakes you, or unexplained weight loss. NCI lists pain and fractures as signs of spread to bone.

• NCI PDQ: renal cell cancer, HP version
• NCI PDQ: renal cell cancer, patient version
• NCI: metastatic cancer
• NCI: immunotherapy side effects
• SEER Stat Facts: kidney and renal pelvis cancer
• Choueiri TK et al. Overall Survival with Adjuvant Pembrolizumab in Renal-Cell Carcinoma. N Engl J Med 2024;390:1359-1371