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What Is Advanced Renal Cell Carcinoma

Chromophobe Renal Cell Carcinoma Symptoms

New Treatment Paradigm for Advanced Renal Cell Carcinoma | Memorial Sloan Kettering

Most people with chromophobe RCC dont have any symptoms at all when they are diagnosed. Instead, the cancer may be discovered on imaging scans done for another reason.

If symptoms are present, they may include the following:

  • Pain in your lower back
  • Blood in your urine

You might experience different symptoms if your cancer has already traveled to other places in your body . In this case, some possible symptoms include:

  • Bone pain

Tumour Heterogeneity And Cancer Evolution

As Nowell first described 40 years ago, genetic diversity within tumours is thought to provide the substrate upon which selection can act, to enable tumours to adapt to new microenvironmental pressures and metabolic demands during the natural history of the cancer . Such genetic diversity has been studied extensively in ccRCC. For example, in a study of four patients with ccRCC who had multiple tumours were subjected to multi-region genetic analysis, VHL mutation and 3p loss of heterozygosity were found to be ubiquitous events across all regions sampled. By contrast, common driver events such as SETD2, PBRM1, MTOR, PIK3CA, PTEN and KDM5C mutations were present heterogeneously within the primary tumour and metastatic sites â in some regions but not others. Such genetic characteristics enable the construction of tumour phylogenies, whereby the âtrunkâ of the evolutionary tree depicts mutations found in the most recent common ancestor that are present in every tumour cell. âBranchedâ mutations are found in some subclones but not others these mutations may be regionally distributed across the tumour, occupying distinct regional niches within the primary tumour or different niches between the primary and metastatic sites of disease.

Cancer evolution and tumour heterogeneity in ccRCC

Renal Cell Carcinoma: Diagnosis And Management

RICHARD E. GRAY, DO, and GABRIEL T. HARRIS, MD, Uniformed Services University of the Health Sciences, Bethesda, Maryland

Am Fam Physician. 2019 Feb 1 99:179-184.

Kidney cancer is one of the 10 most common cancers in the United States with 90% being attributed to renal cell carcinoma. Men, especially black men, are more likely to be affected than women. Renal masses, either cystic or solid, are best detected with contrast-enhanced, triple-phase computed tomography. Renal tumors are often detected incidentally during a computed tomography scan of the abdomen or chest that was ordered for unrelated symptoms. Hematuria serves as a warning sign that necessitates further evaluation and imaging leading to a diagnosis and treatment plan. Treatment options include active surveillance, ablation, nephron-sparing tumor excision, nephrectomy, and systemic treatment. Predictors of a poor prognosis include poor functional status and metastasis. In recent years new therapies have improved the prognosis for patients with metastatic disease. The family physician should be aware of risk factors and lifestyle and dietary modifications that may reduce risk.

Renal cell carcinoma is classified in three major histological subtypes: clear cell , papillary , and chromophobe .4 Disease-specific survival is worst with clear cell renal cell carcinoma as it tends to be discovered at a more advanced stage.5

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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.

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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.

What Causes Renal Cell Carcinoma

Cancer occurs when abnormal cells begin to grow or divide uncontrollably. The abnormal cells crowd out normal cells, causing problems at the site where the cancer started. Cancer can sometimes spread to other organs as well. RCC beings in one or both kidneys.

The kidneys are bean-shaped organs that filter blood and create urine to dispose of the waste. Renal cell cancer affects the lining of small tubules in the kidneys, where the filtration takes place.

Most people have two kidneys one on each side of the lower spine, near the hips. However, its possible to live a healthy life with just one kidney. RCC usually involves one tumor in one kidney, but it also may involve multiple tumors in both kidneys.

Certain factors and lifestyle choices affect your risk of getting RCC. You may have an increased risk of RCC if you:

  • smoke

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Treatment Of Stage Iv And Recurrent Renal Cell Cancer

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

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.

Cn In The Targeted Therapy Era

Treating Advanced Renal-Cell Carcinoma

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 .

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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. .

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.

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Ongoing Randomized Clinical Trials Addressing Cn

To prospectively examine the role of CN in the context of adjuvant-targeted therapy, two large randomized trials are currently ongoing. The Clinical Trial to Assess the Importance of Nephrectomy examines nephrectomy followed by sunitinib treatment compared with sunitinib alone in patients with mRCC. This phase III non-inferiority study was initiated in 2009 and enrolls patients with clear cell mRCC and an ECOG performance status of 0 or 1. The trial has an estimated study completion time of February 2018. Additionally, the EORTC Immediate Surgery or Surgery after Sunitinib Malate in Treating Patients with Metastatic Kidney Cancer trial assesses the timing of nephrectomy relative to treatment with sunitinib in patients with resectable mRCC. SURTIME was initiated in 2010 and randomizes patients with mRCC to either a nephrectomy followed by sunitinib or to three courses of sunitinib therapy with subsequent nephrectomy. The primary and secondary endpoints of the SURTIME trial are PFS and OS, respectively.

The Following Stages Are Used For Renal Cell Cancer:

Nivolumab with ipilimumab recommended through CDF for ...

Stage I

In stage I, the tumor is 7 centimeters or smaller and is found in the kidney only.

Stage II

In stage II, the tumor is larger than 7 centimeters and is found in the kidney only.

Stage III

In stage III, one of the following is found:

  • the cancer in the kidney is any size and cancer has spread to nearby lymph nodes or
  • cancer has spread to blood vessels in or near the kidney , to the fat around the structures in the kidney that collect urine, or to the layer of fatty tissue around the kidney. Cancer may have spread to nearby lymph nodes.

Stage IV

In stage IV, one of the following is found:

  • cancer has spread beyond the layer of fatty tissue around the kidney and may have spread into the adrenal gland above the kidney with cancer or to nearby lymph nodes or
  • cancer has spread to other parts of the body, such as the bones, liver, lungs, brain, adrenal glands, or distant lymph nodes.

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Genetic Alterations Of Her Genes In Chromophobe Renal Cell Carcinoma

  • Affiliations: Department of Chemical Engineering and Biotechnology and Graduate Institute of Biochemical and Biomedical Engineering, National Taipei University of Technology, Taipei 10608, Taiwan, R.O.C., Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan, R.O.C.
  • Pages: 2111-2116
  • This article is mentioned in:

    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

    Clinical features of 11 chromophoberenal cell carcinoma patients.

    Table I.

    Treatment Of Stage Ii Renal Cell Cancer

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

    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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    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

    What Is The Prognosis For People With Ccrcc

    Treating Advanced Renal Cell Carcinoma (RCC)

    The estimate of how a disease will affect you long-term is called prognosis. Every person is different and prognosis will depend on many factors, such as

    • Where the tumor is in your body
    • If the cancer has spread to other parts of your body
    • How much of the tumor was taken out during surgery

    If you want information on your prognosis, it is important to talk to your doctor. NCI also has resources to help you understand cancer prognosis.

    Doctors estimate ccRCC survival rates by how groups of people with ccRCC have done in the past. Because there are so few pediatric ccRCC patients, these rates may not be very accurate. They also dont take into account newer treatments being developed.

    With this in mind, ccRCC patients with smaller tumors have a better chance of survival than patients with larger tumors. The 5-year survival rate for patients with ccRCC is 50-69%. When ccRCC is already large or has spread to other parts of the body, treatment is more difficult and the 5-year survival rate is about 10%.

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    What Is Renal Cell Carcinoma

    Renal cell carcinoma , also called renal cell cancer or renal cell adenocarcinoma, is a common type of kidney cancer. Renal cell carcinomas account for about 90 percent of all kidney cancers.

    RCC usually begins as a tumor growing in one of your kidneys. It can also develop in both kidneys. The disease is more common in men than women.

    Surgical Management Of Advanced And Metastatic Renal Cell Carcinoma: A Multidisciplinary Approach

    • 1Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey and Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, United States
    • 2Division of Medical Oncology, Rutgers Cancer Institute of New Jersey and Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, United States

    The past decade has seen a rapid proliferation in the number and types of systemic therapies available for renal cell carcinoma. However, surgery remains an integral component of the therapeutic armamentarium for advanced and metastatic kidney cancer. Cytoreductive surgery followed by adjuvant cytokine-based immunotherapy has largely given way to systemic-targeted therapies. Metastasectomy also has a role in carefully selected patients. Additionally, neoadjuvant systemic therapy may increase the feasibility of resecting the primary tumor, which may be beneficial for patients with locally advanced or metastatic disease. Several prospective trials examining the role of adjuvant therapy are underway. Lastly, the first immune checkpoint inhibitor was approved for metastatic renal cell carcinoma in 2015, providing a new treatment mechanism and new opportunities for combining systemic therapy with surgery. This review discusses current and historical literature regarding the surgical management of patients with advanced and mRCC and explores approaches for optimizing patient selection.

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