Metastatic Disease: The Landscape

• When the cancer has recurred or spread to distant organs, there is a real chance for long term survival or even cure with the best treatment and this is true even though the prognosis and the odds are poor, as is median survival. (I highly recommend reading The Median Isn't the Message here on CancerGuide to better understand why poor median survival does not preclude the possibility of long term survival or even cure).
  
  
• Renal cell carcinoma, while not truly rare, is also not common and the treatment differs from that of most cancers. Therefore the average oncologist may not have much experience with the disease and its treatment. In my opinion many patients are not offered the best treatment. This means it's important to find experts in the disease and also to do your own research.
  
  
• Many patients are told that renal cell cancer is a slow growing disease, but in truth the word which best characterizes its rate of growth is "variable". While, without effective treatment, the disease usually progresses rapidly, patients occasionally enjoy long periods of stability, even several years, without any treatment at all. Some patients even have their tumors shrink or disappear entirely without treatment.
  
  
• While much is made of so-called "spontaneous remission" in the popular literature on exceptional recoveries from cancer, the truth is that spontaneous remission is exceedingly rare in most types of cancer. Renal cell cancer is one of the few exceptions, and here spontaneous remissions are well documented and are always a reason for hope. These remissions can be complete and long lasting, but are often partial and temporary. Estimates of how often spontaneous remissions occur vary and range from the order of a few percent of cases to a few tenths of a percent of cases. This relatively high rate of spontaneous remission was one early clue that RCC might be one of the cancers most susceptible to immunotherapy.
  
  
• Clinical trials are an important part of this landscape. Because the best treatments are so very far from ideal, many patients who go to major medical centers or recognized experts will be offered clinical trials, and anyone who investigates options on their own will soon be looking at clinical trials. Clinical trials can be a great way to get cutting edge new treatment but they also very greatly in their promise, and are not automatically better than the best standard treatments, especially for first line treatment. For more on how and where to approach investigating clinical trials for advanced RCC, see Clinical Trials for Advanced Kidney Cancer, Promise and Peril

Treatment Overview

• It has long been recognized that surgery for a solitary metastasis can lead to many years of remission and even an occasional cure. In fact, data has gradually accumulated over many years that extends these findings to cases where there is more than just a single metastasis, if all of the tumors can be completely removed. If such surgery would be reasonable for you, this could well be your most likely route to a remission. For two detailed reviews of the emerging data, see Surgery for Metastatic RCC.
  
  
• RCC is one of the few cancers which has been found to be susceptible to immunotherapy. Immunotherapy is therapy which manipulates your natural immune system so it recognizes and destroys cancer cells. Immune stimulating drugs such as Interleukin-2 and Alpha Interferon are the mainstay of current pharmaceutical treatment and immunotherapy. In particular, Interleukin-2 based therapy sometimes yields very long term remissions and apparent cures.
  
  
• Clear cell kidney cancers typically contain a very dense network of new blood vessels that feed the tumor, and furthermore clear cell RCC cells have known genetic defect (non-functioning VHL gene) which specifically drives blood vessel growth. A new approach in cancer therapy called "antiangiogenic therapy" targets tumor blood vessels. While no antiangiogenic therapy for RCC is yet standard this approach is being intensively explored and there are many clinical trials testing antiangiogenic drugs. One antiangiogenic drug, Thalidomide, is in common use as a second line therapy as well as in some more exciting combination trials. A new antiangiogenic drug, Avastin, is about to be approved for colon cancer, and has shown some promise in RCC, where it is being tested further. Other antiangiogenic drugs are in clinical trials.
  
  
• Renal cell cancer is notoriously resistant to cytotoxic chemotherapy drugs. These classic "chemo" drugs interfere with dividing cells in a relatively non-specific way. Given the extensive and very poor record of these drugs, I believe most RCC patients should avoid cytotoxic chemotherapy as sole therapy.
  
  
• Things are different for some of the rarer subtypes of RCC so it's important to know what kind of RCC you have. In particular, long lasting responses to cytotoxic chemotherapy are sometimes possible in sarcomatoid RCC (unlike most types of RCC). Papillary RCC appears to be relatively unresponsive to immunotherapy, again unlike the common clear cell variety. For details, see my article on subtypes of RCC.

Decision Making

Finally, some thoughts on maximizing your chances in the strange and austere landscape that is metastatic kidney cancer... what follows will help you understand how I've evaluated treatment options, and may clarify your thinking or inspire to your own path.

• I think the best strategy is to use the treatment at each point which offers the best current odds given your situation. There are some possible exceptions.
  
  
• When choosing treatments, I prefer to rely on evidence that it helps actual people with RCC rather than results from animal or test tube experiments or results in other cancers. Certainly actual evidence is much better than mere theories.
  
  
• I believe the best proven treatments at this time are Interleukin-2, preferably at high dose, and Surgery. These treatments offer a small but real chance of a long term remission or even cure.
  
  
• It takes years to show the kind of long-term durability these treatments can produce. The odds with these treatments are not satisfactory, but the long term survivals are a precious gem not to be thrown away lightly. The length of time required to get long term results makes it hard to know when a new and promising treatment might actually improve the long-term odds. Unfortunately, very few novel treatments turn out to actually be an advance. Therefore, you should consider novel treatments for first line therapy only if there is strong early evidence to suggest that the new treatment will turn out to be better than the standard first line therapies. This would include a substantially better response percentage in prior studies with those responses holding so far (the longer the follow-up the better).
  
  
• If surgery or IL-2 have been tried without success, then one should be much more open to treatments with only early and uncertain signs of success. Early and uncertain signs of efficacy are much better than no evidence of efficacy.
  
  
• Because this disease itself is such risky business, the risks of the disease virtually always exceed the risk of treatment regardless of what the risks of treatment actually are. Clinical trial consent forms, some doctors, and for those here in the states, perhaps even American culture itself, all tend to focus on the risks. If you want to live, you had better focus on the potential benefits. Keep your eyes on the prize.