Finding a doctor

One of the most important things you can do if you have kidney cysts or tumors is to consult an expert about your treatment. Kidney cancer itself is an uncommon cancer and consists of several types of kidney cancer, or histologies. It may not be possible to find a doctor who has seen and treated many cases of sporadic (non-hereditary) kidney cancer, and this is much more common than the cancer that can be caused by the altered BHD gene.

Birt-Hogg-Dubé is a rare syndrome. It will be difficult for most people to find a doctor who has seen multiple cases of the kidney symptoms associated with the BHD syndrome; it’s quite possible you will be the first. If this is the case, it is preferable to find a doctor who is willing to look at the literature, perhaps speak to other doctors, and to learn about the Birt-Hogg-Dubé syndrome along with you. It is important to establish a follow up plan for monitoring your kidney health once you have a BHD diagnosis because you are at risk for developing kidney tumors.

Kidney symptoms related to the Birt-Hogg-Dubé syndrome will often not be treated in the same manner as you would treat sporadic (non-hereditary) kidney tumors.

The kidney tumors associated with BHD are of different histologies. See the Kidney Symptom page for more details about these types and about the frequency of renal tumors occurring in BHD.. The clear cell and papillary variants occur less frequently in the Birt-Hogg-Dubé syndrome, but may be more likely to metastasize and should be monitored very carefully.

In general, treating or removing the kidney tumors before they reach 3cm in size is recommended. This applies both to the tumors that are found at first, and to those that grow after the original tumors have been treated or removed.

If you research kidney cancer, you may find references to treatments such as Immunotherapy (IL-2), targeted therapies (multi- kinase inhibitors, Sutent, Nexavar), Temsirolimus, an inhibitor of mTOR signalling, Chemotherapy, Radiation and Nonmyleoablative Allogeneic Stem Cell Transplant. The Other Treatments section of this page contains more detailed information about these topics as well as adjuvant therapies, kidney transplants and dialysis, as they relate to BHD.

The goal in treating kidneys of those affected by BHD is to preserve as much kidney tissue as possible for as long as possible.

When you remove kidney tumors associated with BHD, new ones will grow. Clinical studies have shown the therapeutics based on Rapamycin such as Sirolimus, prevent further growth only whilst the drug is being prescribed. Phase III clinical trials are ongoing with this drug in individuals with Tuberous Sclerosis.  This makes early detection of kidney tumor growth and nephron sparing (kidney sparing) treatment a vital part of care for the Birt-Hogg-Dubé syndrome. If you can catch the tumors as soon as possible, in most cases you can remove them early enough to maintain kidney function..

Research seems to indicate that most of the genetic renal cell cancer caused by the Birt-Hogg-Dubé syndrome grows more slowly than sporadic (non-hereditary) RCC. For some people, this means that kidney tumors can be monitored for a longer period of time before surgery is necessary.

It’s possible to live a normal life with just a part of one kidney, if that kidney is functioning well. If you do have to have part of one or both kidneys removed, it is also important to maintain your overall health to help keep normal kidney function.

The first treatment for BHD kidney tumors may be surgery; for later treatments, you may want to consider different option.

Nephrectomy vs. Partial Nephrectomy

For many years, nephrectomy ( removal of the whole kidney) was standard treatment if you had a kidney tumor. In recent years, this has changed. Studies show that partial nephrectomies are just as effective as treatment as the full or radical nephrectomy. For those with the possibility of developing bilateral kidney cancer, removing only part of the kidney is preferable whenever possible.

Your surgeon will determine if a partial nephrectomy is possible or not. In some cases, the location or size of your tumor may make a partial nephrectomy a bad choice. However, it is important that you act as your own advocate and ask some important questions before you schedule your kidney surgery.

1. How many kidney surgeries have you done totally? This year?
   (Over 30 a year is good; over 100 a year is better.)
2. How many partial nephrectomies have you performed?
3. How many laparoscopic partials?
4. If you are telling me I need a full nephrectomy, why?
   Can nothing be done to save part of the kidney?
5. (If you have bilateral or multifocal kidney tumors, or both-
   How many patients have you had with tumors similar to mine?)

Most urologists have training in performing nephrectomies. Technically, this is an easier operation to perform than a partial nephrectomy. However, since partial nephrectomies are preferable whenever possible for those with BHD, it is to your advantage to find an expert who can do a partial nephrectomy, even if it means traveling for the surgery.

Laparoscopic Surgery (Minimally Invasive Surgery)

Both full nephrectomies and partial nephrectomies can be done laparoscopically. This technique involves fewer incisions than traditional surgery, a shorter hospital stay, and usually a less painful, faster and therefore easier recovery. Not all surgeon have experience with laparoscopic procedures, and you may have to seek a second opinion to find someone who can do this technique. 3-4 small (1 cm) incisions in the abdomen are usually made for laparoscopic surgery. A camera and narrow instruments can be inserted into the abdomen via these incisions. The kidney or part of the kidney is placed in a bag and is removed via one of the incisions, which may be enlarged slightly to allow for this.

Nephrectomy

This surgery can be open, hand assisted laparoscopic or laparoscopic. Open surgery involves an flank incision, sometimes stretching from the side to within a few inches of the belly button. Sometimes part of a rib is removed. A hand-assisted nephrectomy involves a smaller incision. More common these days is the laparoscopic nephrectomy.

Partial Nephrectomy (Nephron Sparing Surgery)

During a partial Nephrectomy, the part of the kidney that concerns the cancer is removed. In sporadic (non-hereditary) kidney cancer, this most normally means that one tumor is removed. For someone affected by the Birt-Hogg-Dubeé syndrome, there may be several tumors present when the kidney cancer (renal cell carcinoma) or tumors are found. In these cases, each tumor is cut out or scraped off of the kidney, taking a little healthy kidney tissue at the same time. The kidney may have a pitted look after this type of procedure.

Robotic Partial Nephrectomy

Currently, not all surgeons are experienced in doing partial nephrectomies. With a new piece of robotic equipment, it is possible to perform extremely professional partial nephrectomies. Experts are also using these machines because they make a definitive difference in the precision, control and maneuverability needed during this type of surgery. The instrument also enables the surgeon to take advantage of a 3-D viewing feature.

Natural Orifice Translumenal Endoscopic Surgery (NOTES)

This may, in the future, be an option for those facing kidney surgery, but it is still very new. It is a minimally invasive technique that combines laparoscopic and endoscopic techniques. Instead of making incisions in the body, the instruments for peritoneal cavity surgery are inserted through the body’s natural openings. NOTES has been performed on animals, and in a few cases, on humans. To date there is little information on NOTES and kidney surgery.

Surgical Alternatives

Ablation

Different kinds of ablation may be chosen as a secondary treatment if new kidney tumors grow after a nephrectomy or partial nephrectomy. Currently they are not used too often as the first line of attack.

Radio Frequency and Cryoablation

Radio Frequency Ablation is a technique that uses extreme heat to kill kidney cancer tumors while they are still in the kidney. Cryoablation uses cold. A few years ago, reports were published giving Cryoablation the edge over Radio Frequency Ablation due to fewer instances of recurrence in the margins of the kidney area that was treated. Recent improvements in RFA equipment may have evened out this difference.

Ultrasound Ablation

Ultrasound Ablation is a new technique that allows for a quick, highly targeted treatment. The ultrasound can pass through healthy tissue without damaging it; then high intensity ultrasound heats the targeted tissue, killing it. Proponents of Ultrasound Ablation says it works better than other heat ( thermal) ablations because this process is quicker and more focused. There is not as much information on this technique as there is on Cryoablation and Radio Frequency ablation at the current time.

Microwave Ablation

Microwave Ablation is a new technique that has been used on a few occasions to treat tumors. It utilizes a very high heat and supposedly works very quickly. A thin microwave antenna is guided to the tumor using imaging techniques. This procedure can be used in open, laparoscopic or percutaneous surgery

Other Treatments

United Kingdom and United States Health Care

The health care systems of the U.K. and U.S.A are considerably different. Drugs and other therapeutics may be obtained in the U.S.A once they have been cleared by the Food and Drugs Administration (US FDA). This government sponsored body ensures that all drugs are fit for human consumption. Based on an individuals health insurance policy, drugs approved of by the US FDA may be prescribed by a medical practioner. In the U.K., once drugs have been through the clinical trials process and shown to by effective and safe for human use, they must be approved by the National Institute for Health and Clinical Excellence (NICE), a health economics group that accounts for cost effectiveness. Drugs that are approved can then be obtained freely on the National Health Service (NHS), alternatively private healthcare options are available to UK citizens and non NICE-approved drugs may be obtained privately.

Targeted Therapies

Targeted therapies include:

• Interferon for kidney cancer
• Interleukin 2 for kidney cancer
• Sunitinib for kidney cancer
• Other biological therapies

Interferon for kidney cancer

Interferon is a form of  immunotherapy and it works in several ways:

• it can directly help to stop the cancer cells growing;
• it may also boost the immune system to attack the cancer;
• It may restrict the blood supply to the cancer cells.

You are most likely to have interferon for metastatic kidney cancer.  If you have more than one area of cancer spread in the same organ, it is unlikely to be possible to remove the cancer surgically and your doctor may consider treating you with interferon.  It can help to stabilise or shrink the cancer, rather than make it disappear altogether.  Interferon treatment has been shown to help patients with advanced kidney cancer, particularly when the cancer has spread to the lung.  People who benefited most from this treatment were in good general health, with few cancer symptoms.

Researchers are using interferon as part of a clinical trial after surgery to remove early stage kidney cancer.  The aim is to lower the risk of the cancer coming back in the future. This trial is still recruiting, see here for more information.

The type of interferon used for kidney cancer is called interferon-2a (Roferon-A).  You usually have it 3 times a week, as a small injection just under the skin.

Interleukin 2 for kidney cancer

Interleukin is also called IL-2 or aldesleukin.  It is produced naturally in the body as part of our immune system.  It usually works to stimulate white blood cells (lymphocytes) to fight infection.  IL-2 can now be made in laboratories and is most often used for advanced kidney cancer.

IL-2 is used on its own or in combination with other treatments.  A trial is comparing interferon on its own with a combination of interferon, IL-2 and a chemotherapy drug called 5FU for advanced kidney cancer.  IL-2 is also being tried as a treatment after surgery for early kidney cancer.  The aim of this treatment is to try to lower the chance of the cancer coming back.  Doctors call this adjuvant treatment. For more information on this specific trial, including how to participate, see here.

Sunitinib for kidney cancer

Sunitinib, is also called Sutent.  It comes as a capsule, which you swallow.  It is a type of drug called a tyrosine kinase inhibitor or TKI for short.  It blocks tyrosine kinase in cancer cells.  Tyrosine kinase is a chemical messenger (an enzyme) that sends messages to tell cells to divide and grow.

Research trials in the UK have shown that sunitinib can stop or slow the growth of advanced kidney cancer, see here for more details.

The National Institute for Health and Clinical Excellence (NICE) have issued guidance that sunitinib should be available as a treatment option for people with advanced kidney cancer, if they would be suitable for immunotherapy, and are reasonably fit (for example, well enough to do light house work).

Other biological therapies

Other biological treatments are being used for kidney cancer.  Bevacizumab (Avastin), sorafenib (Nexavar) and temsirolimus (Torisel) have been shown to stop or slow the growth of advanced kidney cancer but the National Institute for Health and Clinical Excellence (NICE) have given guidance that they are currently too expensive for the amount of benefit they give.  So they are not widely available on the NHS in the UK.  You may have them as part of your private health care plan in the UK and they have been approved by the US FDA.

Other treatments are in early research and we have only briefly mentioned them here because they are still very much at the investigation stage and so are not available outside clinical trials. To search for active clinical trials in the area of Kidney Cancer, please see here.

Other biological treatments being developed include

• Vaccines
• New immunotherapy drugs
• Drugs to stop tumours making blood vessels

Vaccines

Vaccines can be made from tumour cells or dendritic cells.  Tumour cell vaccines are made from each individual patient’s kidney cancer cells, removed during surgery.  Dendritic cells are a type of white blood cell.  They are removed from the blood and mixed with kidney cancer cells in a laboratory.  Then, they are injected back into the patient as a vaccine.

New immunotherapy drugs

Immunotherapy drugs are similar to interferon and IL-2.  New drugs include GM-CSF (a growth factor that tells the body to grow white blood cells) and IL-12 (another ‘chemical messenger’ of the body’s immune system).

Drugs to stop tumours making blood vessels

Treatments that stop tumours making blood vessels are called anti-angiogenics.  One drug used to do this is thalidomide.  Thalidomide has been tested in combination with interferon and IL2 for advanced kidney cancer.

Such treatments would have to be given through clinical trials to determine its effectiveness before it could be submitted for FDA approval.

Chemotherapy

Chemotherapy does not normally work on sporadic Renal Cell Carcinoma (RCC or kidney cancer). RCC appears to be extremely resistant to Chemotherapy. There are several Clinical Trials being conducted with Chemotherapy options for kidney cancer, alone or in combination with other therapies, but these trial are not geared towards those affected by BHD.

Radiation

Kidney cancer in general is resistant to radiation. There is therefore no reason to think that radiation would be effective on the multifocal bilateral kidney tumors typical of the Birt-Hogg-Dubé syndrome.

Nonmyleoablative Allogeneic Stem Cell Transplant

This type of stem cell transplant as treatment for Renal Cell Carcinoma has been primarily limited to conventional Clear Cell kidney cancer patients in the past, with sibling or unrelated stem cell donors. There is to our knowledge no research on stem cell transplants for kidney cancer patients with hereditary syndromes.

Adjuvant Therapy

Adjuvant Therapy is treatment that is given after surgery or some kind of prior treatment has left the person with no evidence of disease (NED). Due to the multifocal (multiple tumors or growths) and bilateral (both kidneys affected) nature of Birt-Hogg-Dubé syndrome, and to the fact that the kidney tumors will continue to grow, adjuvant therapy has not been an option for those affected by BHD. There is currently no vaccine and no medication that can be given after the first surgery that can stop the tumor growth in the kidneys. However, researchers are working on options

Kidney Transplant & Dialysis

Theoretically, it should be possible for people with the Birt-Hogg-Dubé syndrome to have a kidney transplant. People with another hereditary syndrome, Von Hippel Lindau, have had successful kidney transplants when the cancer in their kidneys became too advanced. We have no records of kidney transplants in BHD families.

Historically, there is a very long kidney transplant waiting list in many parts of the world. People with cancer may not get a high priority on the waiting lists. Transplants using organs from compatible family members or friends are easier to arrange.

The goal of early detection of kidney tumors and managed care is to avoid dialysis. We have few records of people with the Birt-Hogg-Dubé syndrome who are on dialysis. (Bures et al, Chest 2004 ) If the tumors are discovered early enough, and if the kidney growth can be managed by experts who can help the affected person avoid full nephrectomies, the chance of preventing the need for dialysis are greatly enhanced.

Treatment Methods for Kidney Failure
Kidney Failure
The Kidney Transplant/Dialysis Association, Inc.

Have you had these treatments and can you offer any advice on them, or would you like to know more? Why not post your advice or questions on our forum?

Sources

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  Jorge R Toro, Ming-Hui Wei , Gladys Glenn , Michael Weinreich , Ousmane Toure , Cathy Vocke , Maria L Turner , Maria Merino , Peter Pinto , Seth Steinberg , Laura Schmidt and W Marston
  Linehan
• Evaluation and management of renal tumors in the Birt-Hogg-Dubé syndrome.
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• Microwave Ablation: Principles and Applications Caroline J. Simon, MD, Damian E. Dupuy, MD and William W. Mayo-Smith, MDDOI: 10.1148/rg.25si055501 RadioGraphics 2005;25:S69-S83
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• High-Intensity Focused Ultrasound Ablation: Will Image-guided Therapy Replace Conventional Surgery?
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• Temsirolimus, Interferon Alfa, or Both for Advanced Renal-Cell Carcinoma
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• Medscape (you need to register to view the article)