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What Is Non Clear Cell Renal Carcinoma

What Is Clear Cell Renal Cell Carcinoma

Treating Non-Clear Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma, or ccRCC, is a type of kidney cancer. The kidneys are located on either side of the spine towards the lower back. The kidneys work by cleaning out waste products in the blood. Clear cell renal cell carcinoma is also called conventional renal cell carcinoma.

Clear cell renal cell carcinoma is named after how the tumor looks under the microscope. The cells in the tumor look clear, like bubbles.

Safety And Efficacy Of Nivolumab Plus Ipilimumab In Patients With Advanced Non

This article was originally published here

J Immunother Cancer. 2022 Feb 10:e003844. doi: 10.1136/jitc-2021-003844.


BACKGROUND: CheckMate 920 is a multicohort, phase 3b/4 clinical trial of nivolumab plus ipilimumab treatment in predominantly US community-based patients with previously untreated advanced renal cell carcinoma and clinical features mostly excluded from phase 3 trials. We report safety and efficacy results from the advanced non-clear cell RCC cohort of CheckMate 920.

METHODS: Patients with previously untreated advanced/metastatic nccRCC, Karnofsky performance status 70%, and any International Metastatic Renal Cell Carcinoma Database Consortium risk received up to four doses of nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks followed by nivolumab 480 mg every 4 weeks for 2 years or until disease progression/unacceptable toxicity. The primary endpoint was incidence of grade 3 immune-mediated adverse events within 100 days of last dose of study drug. Key secondary endpoints included objective response rate , progression-free survival , time to response , and duration of response , all using RECIST V.1.1. Overall survival was exploratory.


Other Types Of Non Clear Cell Kidney Cancer

  • Transitional cell carcinoma : They are also known as urothelial carcinomas. TCCs do not start in the kidney but in the transitional cells in the lining of the renal pelvis. This cancer can look like other types of urothelial cancer such as bladder cancer. However, people with TCC will often have the same symptoms as people with kidney cancer, like blood in the urine and back pain. TCC is rare and can be aggressive.
  • Wilms tumor : This tumor almost always occurs in children and is very rare in adults. About 90% of kidney cancers in children are Wilms tumors.
  • Renal sarcoma: This is a rare type of kidney cancer that begins in the blood vessels or connective tissue of the kidney.

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How Does It Spread

If a cancerous tumor is discovered in one of your kidneys, the usual treatment is to surgically remove part or all of the affected kidney.

If the tumor is not removed, its more likely that the cancer will spread to either your lymph nodes or other organs. The spread of cancer is called metastasis.

In the case of RCC, the tumor can invade a large vein leading out of the kidney. It can also spread to the lymph system and other organs. The lungs are especially vulnerable.

How Kidney Cancer Stages Are Determined

ASCO GU 2020: Molecular Pathways and Management Options in ...

Kidney cancer stage is determined through diagnostic testing. Usually, imaging tests will be done to analyze the tumor or tumors within the kidney.

Imaging tests will also be done to identify metastasis in other areas of the body, including the lungs, brain, and bones. These tests may include CT scans, MRIs, a bone scan, and a chest CT or X-ray.

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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.

Is Clear Cell Renal Cell Carcinoma Inherited

Having a sibling with renal cell carcinoma increases your risk of kidney cancer. Experts arent sure why.

Some families have genetic conditions that predispose them to clear cell renal cell carcinoma. These conditions include Von Hippel-Landau disease and tuberous sclerosis complex. With these conditions, an inherited gene change or mutation causes cysts and tumors to form. These cysts and tumors are usually not cancerous . But ccRCC can occur in these families, often at younger ages.

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What Is The Survival Rate For Clear Cell Renal Cell Carcinoma

As many as 7 in 10 people with small ccRCC tumors are alive five years after the initial diagnosis. Treatment is less effective on large tumors or metastatic cancer. In those cases, five-year survival rates may drop to about 1 in 10. A cancer prognosis depends on many factors, including:

  • Cancer spread.
  • Location, size and number of tumors .

Current Perspectives On Nonclear Cell Rcc

Treatment of Metastatic Non-Clear Cell Renal Cell Carcinoma
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    Treatment Of Advanced Tfe3 Kidney Cancer

    Optimal therapy for unresectable translocation RCC remains under investigation. At least two case series have evaluated the role of VEGF-pathway antagonists in this disease. In a retrospective study of 15 patients with translocation RCC , who were treated with one of a variety of inhibitors of the VEF axis, three partial responses and seven patients with stable disease were noted. Median PFS and OS were 7.1 months and 14.3 months respectively. Investigators from the French Juvenile RCC Network reported their experience in twenty one patients with metastatic TFE3 tumors treated with systemic therapy. Four of eleven patients receiving sunitinib in the first line setting had an objective response, with a median PFS of 8.2 months. Responses were also seen in patients receiving this agent as well as those receiving an mTOR inhibitor as salvage therapy following failure of first line agents.

    Regimen Highly Active Among Certain Patients With Non

    Lee CH, et al. Abstract E43. Presented at: International Kidney Cancer Symposium Nov. 5-6, 2021 Austin, Texas.

    Disclosures: We were unable to process your request. Please try again later. If you continue to have this issue please contact .

    The combination of cabozantinib and nivolumab showed promising efficacy for certain patients with metastatic non-clear cell renal cell carcinoma, according to phase 2 study results presented at International Kidney Cancer Symposium.

    Researchers observed the most activity among patients with papillary, unclassified or translocation-associated histologies. The regimen appeared less active among patients with chromophobe renal cell carcinoma.

    The combination also exhibited an acceptable safety profile.

    Cabozantinib and nivolumab is highly active in patients with select non-clear cell histologies, and accurate characterization of the tumor histology remains a key clinical determinant in outcomes to systemic therapy, researcher Chung-Han Lee, MD, PhD, medical oncologist at Memorial Sloan Kettering Cancer Center, told Healio.

    Clear cell renal cell carcinoma accounts for 60% to 80% of kidney cancer cases. Other subtypes collectively are grouped as non-clear cell renal cell carcinoma however, this classification comprises multiple heterogeneous malignancies, according to study background.

    Chung-Han Lee

    Researchers divided patients into two cohorts.

    Median follow-up was 13.1 months .

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    What Are The Treatment Options For Renal Non

    The treatment for Renal Non-Clear Cell Carcinoma may be decided based on different factors including the stage and extent of spread of the cancer, cancer characteristics, symptoms, patients general health and medical history, and whether the cancer was just diagnosed or had come back. The treatment options for Renal Non-Clear Cell Carcinoma include:

    • Surgery
    • Targeted Therapy
    • Immunotherapy

    As part of the diet, avoid including those foods and supplements that may adversely interact with the treatments for this cancer.

    Rare Non Clear Cell Rcc Subtypes

    clear cell papillary renal cell carcinoma
    • Collecting duct carcinoma: A very rare and aggressive type of RCC. At initial diagnosis, it is usually metastatic and has spread to other parts of the body. It is more common in younger people.
    • Translocation RCC: A rare type of kidney cancer. This cancer can be identified by seeing mutations, or changes, in a gene called TFE3. This type affects children and young adults but can also affect older adults.
    • Renal medullary carcinoma : This is a very rare type of kidney cancer. It affects young people who carry the sickle cell trait or have sickle cell disease. These cancers are usually metastaticspread to other parts of the bodyat diagnosis.
    • Unclassified RCC: Less than 1% of RCCs are unclassified. They are very rare and do not easily fit into one of the more common subtypes. They tend to be more aggressive.

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    Hereditary Leiomyomatosis Renal Cell Carcinoma: Type 2 Papillary Kidney Cancer

    Hereditary leiomyomatosis and renal cell carcinoma is an autosomal dominant hereditary cancer syndrome in which affected individuals are at risk for the development of cutaneous and uterine leiomyomas and RCC. , The cutaneous leiomyomas may appear as raised, reddened lesions that can occur in clusters on the trunk, limbs or face. The uterine leiomyomas are highly penetrant, can be multiple and are early onset . HLRCC is characterized by germline mutation of the Krebs cycle enzyme gene, fumarate hydratase. â Patients affected with HLRCC are at risk for the development of renal cysts and a very aggressive form of type 2 papillary RCC. , HLRCC-associated kidney cancers can be bilateral and/or multifocal and can form inside renal cysts. Whereas HPRC tumors, which are type 1 papillary kidney cancer, tend to be encapsulated and slow growing, HLRCC renal tumors have a tendency to infiltrate deeply into the renal parenchyma and can spread when the tumors are very small . Management of localized HLRCC-associated kidney cancer involves surgical resection of localized tumors. Active surveillance is not recommended for HLRCC-associated kidney cancers and surgical treatment involves wide excision of localized tumors. Partial nephrectomy is recommended when feasible as these patients have a life-long risk for the development of bilateral, multifocal kidney tumors.

    Papillary Renal Cell Carcinoma

    Papillary RCCs originate from cells of the proximal convoluted tubule . Papillary RCCs can be divided, based upon clinical characteristics and genetic features, into type 1 and type 2 tumors .

    Papillary RCC Type 1

    Patients with type 1 tumors have a better prognosis and are diagnosed at an earlier stage compared to type 2 tumors . Several immunohistochemical markers were proposed to distinguish both types of papillary RCC. However, none of the markers are validated to be used in daily practice. Besides rare hereditary forms characterized by germline mutation in the MET gene , in 15-20% of sporadic papillary type 1 cancers somatic mutations in the MET gene can be found . Alterations in the MET gene or variations of chromosome 7 carrying the MET gene are more frequent and were described in 81% of patients with type 1 carcinomas . This suggests an important role of MET in the pathophysiology of type 1 carcinomas, and MET could be a therapeutic target which is currently investigated in clinical trials.

    Papillary RCC Type 2

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    What Is Kidney Cancer

    Kidney cancer starts in the cells of the kidney. A cancerous tumour is a group of cancer cells that can grow into nearby tissue and destroy it. The tumour can also spread to other parts of the body.

    The kidney is part of the urinary system. The 2 kidneys are on either side of the backbone, deep inside the upper part of the abdomen.

    On the top of each kidney is an adrenal gland. The kidneys make urine by filtering water and waste material from the blood. Inside each kidney is a network of millions of small tubes called nephrons. Each nephron is made up of a tubule and a corpuscle. Tubules are tiny tubes that collect the waste materials and chemicals. Corpuscles have a clump of tiny blood vessels that filter the blood.

    Cells in the kidneys sometimes change and no longer grow or behave normally. These changes may lead to non-cancerous conditions such as cysts. They can also lead to non-cancerous tumours such as papillary renal adenoma.

    But in some cases, changes to kidney cells can cause kidney cancer. Most often, kidney cancer starts in the cells that line the tubules. This type of cancer is called classic renal cell carcinoma, or clear cell carcinoma. Cancers that start from other cells in the kidney are called non-clear cell carcinoma.

    Rare types of kidney cancer can also develop. These include renal sarcoma and primary renal lymphoma.

    Succinate Dehydrogenase Kidney Cancer

    Systemic treatment options for patients with metastatic non-clear cell renal cell carcinoma

    Succinate dehydrogenase kidney cancer is a hereditary cancer syndrome in which affected individuals are at risk for the development of pheochromocytomas, paragangliomas and RCC. , These patients are characterized by germline mutations of the SDHB, SDHC or SDHD genes. â Patients affected with SDH-RCC can develop oncocytic renal tumors, clear cell or papillary RCC. SDH-RCC can be an aggressive form of RCC which has the potential to metastasize when the tumors are small. Management of localized SDH-RCC associated kidney tumors involves surgical resection when the kidney tumor is detected. Active surveillance of small SDH-RCC renal tumors is not recommended.

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    Ongoing Clinical Trials For Non

    Several clinical trials are currently evaluating a wide range of therapeutic approaches in patients with non-clear cell RCCs. Since many of these RCC variants are relatively uncommon entities, most trials are not subtype specific. The activity of everolimus monotherapy in advanced papillary RCC is currently being investigated in an ongoing phase II, single arm, multicenter, European trial . Two randomized phase 2 trials comparing everolimus with sunitinib in previously untreated patients with advanced non clear cell RCC are currently accruing patients , while a Korean phase II study evalauting single agent pazopanib in this population is expected to commence accrual soon. Lastly, combinations of bevacizumab with erlotinib or with everolimus are also being evaluated in papillary RCC patients. It is hoped that these relatively large phase 2 studies will shed further light on the activity of VEGF and mTOR pathway antagonists in pRCC.

    Phase Ii Study Of Neoadjuvant Cabozantinib In Patients With Locally Advanced Non

    Based on the findings from the Phase II study , neoadjuvant cabozantinib was safe and induced a reduction in tumor size in all patients with locally advanced nonmetastatic ccRCC. According to the results from the analysis, 17 patients with biopsy-proven clear-cell RCC were treated with neoadjuvant cabozantinib at a starting dose of 60 mg once per day for 12 weeks.

    The results of this investigation revealed that all of the patients tumors had shrunk. Five patients experienced a partial response, while 12 patients had stable disease. The patients who were given cabozantinib did not experience disease progression. The original kidney tumor was shrunk by a median of 23%. Cabozantinib was clinically active and safe in the neoadjuvant setting in patients with locally advanced nonmetastatic clear-cell RCC.

    Analyst opinion: A larger clinical trial is needed to further establish the role of presurgical treatment in Renal Cell Carcinoma. This will allow us to understand the long-term role of those treatments. Considering that researchers have already witnessed the increased response rates with Cabozantinib in the metastatic setting and the drug has now shown a safe response in the neoadjuvant setting, we look forward to some exciting data in late phase trial as well.

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    Tuberous Sclerosis Complex: Tsc1/2

    Tuberous sclerosis complex is a hereditary hamartoma syndrome in which affected individuals are at risk for the development of multisystem manifestations, including neurologic dysfunction and CNS tumors, cutaneous angiofibromas, pulmonary lymphangiomyomatosis and renal tumors. TSC-associated renal tumors are predominantly angiomyolipomas however, TSC patients are also at risk for the development of clear cell, papillary and chromophobe RCC. ,

    The knowledge that TSC1/2 genes are in the LKB1/AMPK/TSC/mTORC1 pathway has provided the foundation for the development of rational approaches for TSC-associated renal tumors. In a first step in the development of a therapeutic approach for TSC-associated renal tumors Bissler, et al. reported shrinkage of TSC renal tumors with treatment with rapamycin.

    What Is The Difference Between Clear Cell Renal Cell Carcinoma And Papillary Renal Cell Carcinoma

    Kidney Clear Cell Renal Cell Carcinoma

    Clear cell and papillary renal cell carcinomas are types of kidney cancer that cause similar symptoms. Treatments are also similar. The main difference is how your kidney cancer cells look under the microscope. Papillary cancer cells resemble long, thin, finger-like growths. Healthcare providers call these growths papillae. About 1 in 10 people with renal cell carcinoma have the papillary type.

    A note from Cleveland Clinic

    Clear cell renal cell carcinoma is the most common kidney cancer diagnosis. It can be aggressive and grow faster than other kidney cancers. Surgery, called a nephrectomy, is usually the first step to confirm a diagnosis and treat the cancer. Surgery can remove just the cancerous tumor or your entire diseased kidney. You may also benefit from follow-up therapies like immunotherapy or radiation therapy.

    Last reviewed by a Cleveland Clinic medical professional on 01/01/2022.


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    What Is Clear Cell Carcinoma

    Clear cell carcinoma , also sometimes called clear cell cancer, is a rare type of tumor characterized by cells that are clear or pale in color. These cells have a solid boundary and tend to be either filled with fluid or glycogen, a form of glucose. This type of cell can be found in many different types of tumors, but they are often found in the female reproductive system and lower urinary tract.

    Areas of the Body Affected by CCC

    Carcinoma tumors arise from epithelial cells, which are cells that make up the surface of body tissue and cavities. Clear cell carcinoma, therefore, can be found throughout the body in both men and women in the breasts on the skin in the lower urinary tract, particularly the kidney or the organs of the female reproductive system, including the ovaries, vaginal tract, and uterus.

    Clear cell renal carcinoma, also known as renal cell carcinoma , originates in the renal tubules of the kidney. These are the small tubes that remove waste products from the blood. RCC is a very common type of kidney tumor nine out of ten kidney tumors are of this type, and seven out of ten of RCC tumors are clear cell tumors.


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