Genitourinary Cancer – 15 – Kidney

(All the articles published in past are available at www.shyamhemoncclinic.com/blog/)

Genitourinary Cancer PART – 15

Question: Thank you Chiragbhai for important points related to kidney cancer: 1. Early stage cancers have excellent results with only surgery. No role for postoperative radiotherapy or chemotherapy. 2. In early stages, partial kidney removal is also an option, rather than the old surgery of removing whole kidney. 3. Advance stages, even with tumors extending to vena cava or atrium can be resected nowadays. 4. New equipments like use of laparoscope or robot does not improve cure rates. And must be done by very experienced surgeon only, otherwise cure rate may even be lower. This is IMPORTANT, since the new techniques cost several times more, without most people realizing the lack of survival benefit. 5. Very small incidentally detected tumors, in elderly or frail patients, can even be observed without surgery.

Now, what about cancers which are detected in stage 4 or relapse after initial surgery?

Answer: This is the area with marked scientific advances in last about one decade. Previously systemic therapy in kidney cancer was limited to only chemotherapy with very little benefit. Second option was immunotherapy i.e. interferon alpha, again with limited benefit, and difficult to tolerate. One old option with excellent long term responses has been high dose IL-2 injection. However, this is a very difficult treatment to deliver, due to toxicity. Hence very few centers worldwide offered this therapy, even in past when there were few options. One of the center was where I trained in New York, Albert Einstein College of Medicine. And I remember how toxic and difficult it was. It continues to be an option for fit, young patients due to the benefit of very long term responses, however in only about 10-20% patients. And there is no way to know who is likely to benefit.

It is IMPORTANT however to remember that most patients even in stage 4 should be offered removal of affected kidney, as it has been shown to improve survival in randomized trial. Also, some patients with limited metastases, such as only to lungs, especially in small numbers, can be treated with surgery, and systemic therapy can be avoided. Some of these patients will have very long term control. Resection of lung metastases can be done by new methods like LASER resection as well.

Que: Oh! Then what about new medicines?

Ans: New medicines have several advantages. And of course some disadvantages too!

These are all non chemotherapy agents, with overall better safety profile. Many of these are oral, in tablet forms, hence very convenient. And some of them do provide long lasting control, without the toxicity of high dose IL-2.

Main disadvantage is cost, ranging from about Rs 10,000 per month to Rs 2 lac per month. To be given for several months to years until progression. As in most stage 4, metastatic cancers, these are not curative.  One agent may continue to work for several months to over a year, generally followed by progression of disease, requiring switch to next agent. Side effects are less compared to chemotherapy, but not very low. Small subset of patients may have serious side effects (including life threatening) or major intolerance, necessitating change to different drug. Many side effects are unique compared to chemotherapy, and oncologists are still learning how to identify early, and manage.

Que: What are the main new medicines?

Ans: They can be broadly divided in following categories:

1. Tyrosine kinase inhibitors: such as Sunitinib (first such approved agent), pazopanib, sorafenib, axitinib, and latest in the list is cabozantinib. All these are oral. In general, these agents are used most commonly.
2. mTOR inhibitors: everolimus, temsirolimus.
3. VEGF inhibitors: Bevacizumab (generally combined with Interferon alpha).
4. Immunotherapy: nivolumab (a check point inhibitor), ipilimumab. These two are preferably used in combination, however nivolumab is frequently used alone, more so in India, due to cost mainly. These agents provide long term control in a small subset of patients. Same as IL-2, there is no way to find who are likely to benefit. Several other check point inhibitors are approved for other cancers, and soon they are likely to be available for kidney cancer too.

Making a choice among these agents is not easy. There are some guidelines to suggest, with fairly large overlap. Some scoring systems, like MSKCC model, give three risk levels. Low risk patients are preferably given tyrosine kinase inhibitors, with first two preferred. Intermediate or high risk are preferably started with 4^th option i.e. immunotherapy or Cabozantinib. Above is true for most common histology i.e. Clear cell.

For non clear cell histology, preferred option is sunitinib, everolimus or others, but overall with less results compared to that for clear cell histology. Non clear cell is more resistant in general.

December 14th 2018. Dr. Chirag A. Shah; M.D. Oncology/Hematology (USA), 079 26754001. Diplomate American Board of Oncology and Hematology. Ahmedabad. drchiragashah@gmail.com