Is Renal Cell Carcinoma Curable

Conflict Of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The Associate Editor Jose A. Karam declares that, despite having collaborated with author James J. Hsieh, the review process was handled objectively and no conflict of interest exists.

Transitional Cell Carcinoma Of The Kidney

Transitional cell carcinoma of the kidney is rare. It starts in the transitional cells located in the lining of the renal pelvis. Transitional cells stretch or change shape to accommodate the flow and storage of urine.

When the tumor is superficial and there is no spread, this type of cancer is curable in around 90% of patients. Deeply invasive tumors that remain confined to the renal pelvis have a cure rate of 10%15%. Once metastasis has occurred, a cure is no longer possible. However, treatments may help reduce spread and prolong life.

Ongoing Studies And Novel Approaches

Several ongoing phaseIII studies are evaluating TKI-ICI combinations with results expected in the next 1224months. The combination of PD-1 inhibitor toripalimab plus axitinib is being evaluated versus sunitinib as first-line treatment in advanced RCC. In the first study to utilize an alternative to sunitinib as a comparator, COSMIC-313 will add cabozantinib to the nivolumab/ipilimumab doublet in patients with IMDC intermediate/poor risk, with the ICI doublet as the control arm.

Studies are also evaluating regimens that include novel agents, such as those targeting the immune checkpoint LAG-3 and HIF-2, as well as cancer vaccines . Ongoing phase III studies that are evaluating novel agents for first-line treatment of RCC include: PIVOT-09, which is assessing the pegylated interleukin-2 molecule bempegaldesleukin plus nivolumab versus sunitinib or cabozantinib and the combination of pembrolizumab plus lenvatinib with or without the HIF-2 inhibitor belzutifan or the CTLA-4 inhibitor quavonlimab. In the randomized phaseII MERECA study, the dendritic cell vaccine ilixadencel followed by sunitinib was compared with sunitinib as a first-line treatment, with improved ORR but similar PFS and OS results.

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When Kidney Cancer Metastasizes

Stages 3 and 4 indicate that the cancer has metastasized, or spread to other parts of your body. Kidney cancer spreads through blood, lymph nodes, or by direct extension of the original cancerous tumor into nearby tissue or structures.

• Stage 3 means the cancer is also present in a lymph node near the kidney, or in a main kidney blood vessel or fatty tissue around the kidney.
• Stage 4 means the cancer has spread to the adrenal gland on top of the kidney or to another organ or distant lymph nodes.

Collecting Duct And Other Rare Forms Of Rcc

Collecting duct RCC is a rare but highly aggressive tumor of the distal nephron that shows LOH of chromosome 1q, 6p, 8p, 13q and 21q . Mapping of chromosome 1q , 8p and 13q have narrowed down the region but not yet identified the target suppressor genes. Renal medullary carcinoma described in African-Americans and associated with sickle cell trait, mucinous tubulocystic RCC and other rare forms of RCC have been reviewed in Srigley and Delahunt 2009 .

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Treatment Of Stage I Renal Cell Cancer

For information about the treatments listed below, see the Treatment Option Overview section.

• Arterial embolization as palliative therapy.
• A clinical trial of a new treatment.

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

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The best way to cite this PDQ summary is:

PDQ® Adult Treatment Editorial Board. PDQ Renal Cell Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated < MM/DD/YYYY> . Available at: . Accessed < MM/DD/YYYY> .

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Strategies To Improve Treatment Of Stage I

The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. Areas of active investigation aimed at improving the treatment of renal cell cancer include the following:

Adjuvant therapy: Cancer may recur following treatment with surgery because small amounts of cancer had already spread outside the kidney prior to the cancers surgical removal. It is currently estimated that 20-30% of early-stage cancers recur within three years of surgery. Recurrence most commonly occurs in the lungs.

Treatment with systemic therapy after surgery is called adjuvant therapy. Historically, adjuvant therapy with radiation therapy, chemotherapy, or immunotherapy has not been proven to be effective when administered after surgery. However, newer precision cancer medicines and immunotherapies being used in the treatment of metastatic renal cell cancer are now being evaluated as adjuvant therapy for patients with early-stage disease patients should discuss the risks and benefits of participating in a clinical trial evaluating new adjuvant therapies with their physician.

References

Nonmyeloablative Allogeneic Stem Cell Transplantation

Nonmyeloablative allogeneic stem cell transplantation can induce sustained regression of metastatic renal cell carcinoma in patients who have had no response to conventional immunotherapy. In one trial, 19 patients with refractory metastatic renal cell carcinoma who had suitable donors received a preparative regimen of cyclophosphamide and fludarabine, followed by an infusion of peripheral blood stem cells from a human leukocyte antigen identical sibling or a sibling with a mismatch of a single HLA antigen. Patients with no response received as many as three infusions of donor lymphocytes.

Two patients died of transplantation-related causes, and eight died from progressive disease. In 10 patients , metastatic disease regressed three patients had a complete response, and seven had a partial response. The durations of these responses continue to be assessed. Further trials are needed to confirm these findings and to evaluate long-term benefits.

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Clinical Outcomes In Metastatic Nccrcc

Data from the International Metastatic Renal Cell Carcinoma Database Consortium show that the diversity of renal tumors is not just limited to their biologic blueprints, but is reflected in its behavior, which impacts clinical outcomes as well . nccRCC patients had a significantly worse overall survival than their clear cell counterparts . The nccRCC patients were then subdivided into specific histologies, revealing the best survival among patients with chromophobe tumors, followed by papillary tumors, and then unclassified.

Figure 1. KaplanMeier estimates of overall survival in all patients with clear cell histology vs non-clear cell histology.

Mammalian Target Of Rapamycin Signaling Pathway

The constitutively activated mTOR signaling pathway plays a significant role in the tumorigenesis and growth of RCC. The mTOR pathway can be activated by cancer cells via different mechanisms, including loss of p53, mutations in upstream components of PI3K , and paracrine growth factor production, or via mTOR complexes such as TSC1/2, PTEN, Lkb1, and Nf1.42 mTOR inhibitors, also known as rapalogs , inhibit the phosphorylation of mTOR, resulting in altered translation of messenger RNA that codes for the proteins involved in cell survival, cell proliferation, and angiogenesis.42

Temsirolimus, an mTOR inhibitor, was compared with IFN- in a phase III Global Advanced Renal Cell Carcinoma three-arm trial involving patients with previously untreated, poor-prognosis mRCC, divided into treatment groups with temsirolimus, IFN-, and a combination of temsirolimus and IFN-. The temsirolimus arm demonstrated superior OS versus IFN- , although the addition of temsirolimus to IFN- in the combination group did not show any improved survival versus IFN- alone.43 Temsirolimus is indicated for use in intermediate- and especially poor-risk patients in the first-line setting under select circumstances .93

Other approved therapies include selective monoclonal antibodies, such as bevacizumab, directed against VEGF, which also inhibit angiogenesis and therefore impede tumor growth.44

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Genetic Alterations Of Her Genes In Chromophobe Renal Cell Carcinoma

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Abstract

Introduction

Chromophobe renal cell carcinoma is thethird most common subtype of kidney cancer and accounts for ~5% ofall RCC cases. The 5-year disease-free survival rate of chRCC isreported to be increased compared with that of other RCC subtypes,including clear cell, sarcomatoid and papillary renal cellcarcinoma . Although theoutcomes of chRCC are typically more favorable compared with thoseof other subtypes, the disease still demonstrates a 67%probability of tumor progression and metastasis .

Histologically, chRCC consists of large polygonalcells with a slightly reticulated cytoplasm, and with clear and/oreosinophilic cells . The similarities between the histologicalfeatures of chRCC and oncocytoma, a benign tumor of the kidney, maylead to the misdiagnosis of chRCC .

The roles of other HER family genes, including HER1,HER3 and HER4, have not been well studied in chRCC. The presentstudy aimed to investigate the abnormalities of the HER family andassess a potential association with chRCC.

Materials and methods

Table I.

What Is Renal Cell Carcinoma

It’s the most common type of kidney cancer. Although itâs a serious disease, finding and treating it early makes it more likely that youâll be cured. No matter when youâre diagnosed, you can do certain things to ease your symptoms and feel better during your treatment.

Most people who have renal cell carcinoma are older, usually between ages 50 and 70. It often starts as just one tumor in a kidney, but sometimes it begins as several tumors, or itâs found in both kidneys at once. You might also hear it called renal cell cancer.

Doctors have different ways to treat renal cell carcinoma, and scientists are testing new ones, too. Youâll want to learn as much about your disease as you can and work with your doctor so you can choose the best treatment.

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What Is Kidney Cancer

Kidney cancer is cancer that starts in the cells of the kidney. The most common type of kidney cancer is renal cell carcinoma , accounting for about 90% of all cases. Usually only one kidney is affected, but in rare cases the cancer may develop in both kidneys.

Other less common types include:

• Uroethelial carcinoma which can begin in the ureter or renal pelvis where the kidney and ureter meet. It is generally treated like bladder cancer.
• Wilms tumour, which is most common in younger children although it is still rare.

It is estimated that 4377 people in Australia will be diagnosed with kidney cancer in 2021. Kidney cancer is more common in men – the risk of being diagnosed by age 85 is 1 in 47 for men compared to 1 in 100 for women.

The five year survival rate for kidney cancer is 79%.

Renal Cell Cancer Is A Disease In Which Malignant Cells Form In Tubules Of The Kidney

Renal cell cancer is a disease in which malignant cells are found in the lining of tubules in the kidney. There are 2 kidneys, one on each side of the backbone, above the waist. Tiny tubules in the kidneys filter and clean the blood. They take out waste products and make urine. The urine passes from each kidney through a long tube called a ureter into the bladder. The bladder holds the urine until it passes through the urethra and leaves the body.

Cancer that starts in the ureters or the renal pelvis is different from renal cell cancer. .

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Chemotherapy Immunologic Therapy Targeted Therapy

There are several medications approved for treatment of renal cell carcinoma:

• Chemotherapy destroys actively growing cells
• Immune therapy uses a process that triggers your immune system to destroy tumor cells
• Targeted therapy is a type of therapy that specifically destroys the tumor cells

All of these medications are powerful, and they may produce serious side effects during your treatment and recovery.

Adjuvant And Neoadjuvant Therapy

Adjuvant therapy, which refers to therapy given after a primary surgery, has not been found to be beneficial in renal cell cancer. Conversely, neoadjuvant therapy is administered before the intended primary or main treatment. In some cases neoadjuvant therapy has been shown to decrease the size and stage of the RCC to then allow it to be surgically removed. This is a new form of treatment and the effectiveness of this approach is still being assessed in clinical trials.

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Cancer May Spread From Where It Began To Other Parts Of The Body

When cancer spreads to another part of the body, it is called metastasis. Cancer cells break away from where they began and travel through the lymph system or blood.

• Lymph system. The cancer gets into the lymph system, travels through the lymph vessels, and forms a tumor in another part of the body.
• Blood. The cancer gets into the blood, travels through the blood vessels, and forms a tumor in another part of the body.

The metastatic tumor is the same type of cancer as the primary tumor. For example, if renal cell cancer spreads to the bone, the cancer cells in the bone are actually cancerous renal cells. The disease is metastatic renal cell cancer, not bone cancer.

Combined Immune Checkpoint Inhibitors And Antiangiogenic Targeted Therapies

After immune checkpoint inhibitors and antiangiogenic targeted therapies were found to improve outcomes, the combination of these two approaches has been studied in clinical trials and shown to result in longer OS when compared with monotherapy.

Pembrolizumab plus axitinib

Evidence :

Avelumab plus axitinib

Evidence :

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Cn In The Targeted Therapy Era

In the past decade, the systemic management of mRCC has changed significantly, as our understanding of the molecular biology of RCC has increased . Multiple-targeted therapies that primarily inhibit VEGF and mTOR pathways have been approved for the management of mRCC . In light of the efficacy of TT agents, the utility of nephrectomy in patients with mRCC has been questioned. In fact, recent reports indicate declining utilization rates of CN in the TT era . An analysis of the SEER database by Tsao et al. showed that the rate of CN performed was about 50% in patients with stage IV RCC until 2005, when TTs were approved by the FDA. There was then a steady decrease to 38% in 2008, possibly due to the yet unknown interaction between CN and TT and an unwillingness to subject patients to the morbidity of surgery given the benefits of TT . Currently, evidence supporting the role of CN in the TT era for the management of mRCC remains limited and is primarily based on retrospective series and administrative databases.

Table 1. FDA-approved therapies for renal cell carcinoma with their pivotal trial parameters.

Choueiri et al. reported on 314 patients with mRCC treated with adjuvant anti-VEGF-targeted agents and concluded that those who previously underwent CN lived a median of 10 months longer . Although patients who underwent CN had fewer negative predictors of survival , when controlled for known prognostic factors, CN still demonstrated a significant OS benefit .

Early Stages Of Kidney Cancer

Once kidney cancer is confirmed, your medical team will determine the stage of the cancer. The stage is based on how much or how little the cancer has spread.

• Stage 1 means the cancer is only in the kidney, and the tumor is 7 centimeters long or smaller.
• Stage 2 means the cancer is still contained to the kidney, but the tumor is larger than 7 centimeters.

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