Advanced Kidney Cancer -A Glimpse into Future

Dear All,

With all the advances of Early Detection and Treatment for Urological Cancers, there are several cases that progress into advanced stages or even detected in their late stages. Prolongation of life with some quality, irrespective of costs involved, are the way of present day thinking. Recently with advances in Medical Oncology based on understanding of the disease process better, many drugs have appeared making them available for front line to even 4th line as in Kidney Cancers.

I am providing the Excerpt of a talk given by Toni Choueiri at SUO 2020 on ‘Advanced Kidney cancer – A Glimpse into Future’. He has given an overview of the various drugs now being utilized along with those still under trials showing benefits to some extent. This explosion of knowledge is fast becoming a necessity when considering management of Advanced Kidney Cancer.

This excerpt addresses all the relevant aspects that we have to know in this complex subject.

With warm regards,


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  • Venugopal P
    Venugopal P
    10 Dec 2020 10:00:32 AM

    Dear All,

    To add more information to the previous post on ‘Advanced Kidney Cancer’, I am providing an article on ‘Genomic profiling in Renal Cell Carcinoma’ by Nazli Dizman, Sumanta K Pal* et al (2020) which will add to our understanding of RCC.

    The two when read together will vastly improve our knowledge.

    Science waits for no one. It is fluidic and keeps progressing, at times much to our annoyance. But with the exploding knowledge, it has become imperative that we develop a sound knowledge of all happening in the field.

    With warm regards,



  • Dr. Roy Chally
    Dr. Roy Chally
    10 Dec 2020 08:36:10 PM

         There is an ongoing explosion in knowledge. Urology is now a broad speciality with well established sub specialities, urooncology, paediatric urology and andrology. Endourology is still 70% of work in urology in a hospital. A urologist should be knowledgeable and fully competent in endourology. One cannot expect a urologist to be proficient in the sub specialities in urology after his training for M. Ch / dip NB.  We should be clear about this in training a urologist. 

        Coming to the molecular advances in renal cancer,  the direction of research now is to seek ways to treat advanced disease with better understanding the genome of the host and of the cancer and the epigenetic factors. The genomic structure changes with treatment with need to discover new drugs. I do not think that this approach will take us to solve the problem. 
        Cancer is a foreign tissue in the body. Our immune system is not able to destroy the foreign cancerous cells when it surfaces. We are slowly understanding the reasons for this phenomenon. It is reasonable to presume that there should be a signature or marker in our body fluids or in our genome or epigenetic of the occurrence of early cancer.  If we are able to detect such early small volume cancer we should see medication to cure cancer at the early stage when the cancer genome is not very complicated. Will the surgeons role in treating cancer may become secondary? 

  • Amrith Raj Rao
    Amrith Raj Rao
    15 Dec 2020 12:11:56 AM

    Dear Prof, 

    One of the most exciting areas in Uro-oncology is the treatment of RCC, especially metastatic. Before one can grasp the "latest guideline", a trial shows superiority of a new drug, makes the guideline obsolete. Indeed, one of the medical oncologist quipped that one day Surgery will no longer be necessary for RCC! 

    For example - CARMENA trial about cytoreductive nephrectomy (with all its flaws) was to do with Sunitinib. With a availability of more potent immunotherapy, the trial has become "obsolete" and newer trials have began/ongoing. 

    Just to give an example - please read this case report

    Yes, of course, you will always say "One Swallow does'nt make a summer" :-) 

  • Venugopal P
    Venugopal P
    15 Dec 2020 09:17:24 AM

    Dear All,

    I had requested Makarand to write a commentary for the post ‘Advanced Kidney Cancer -A Glimpse into Future’ which has been addressed by Roy and Amrith as well. Amrith had given a link concerning an article which he recommended for our reading. I am posting the PDF link for the same.

    Below you will find the write up of Makarand and hopefully all will benefit from it.



    Thanks for asking me to review the article on Genomics in Nature's reviews as well as synopsis of Tony Chourie's talk at SUO 2020. 

    To make it simpler for the readers / audience of Uro Academy, where do we stand on this issue of advanced RCC and as a practicing urologist and  what one should know , I am making following points.

    In the past, we did not have much in our armoury  in terms of effective therapy when we had a patient of metastatic and locally advanced RCC . Majority of us heavily relied on ( and still most of us  do as of today ...)  radical /cytoreductive nephrectomy ( CRN)  and used  drugs such as IF -alpha , IL_2  ( Immunotherapy era)  till about 7-8 years ago  and now we are using drugs such as Sunitinib , Sorafenib , Pazopanib , Axitinib (  Targeted Therapy era  , TKIS and mTOR inhibitors) .  Immune Checkpoint inhibitors have ( IO) now shown some exciting  results especially Pembro  and now we are moving towards the combination of  Immune check inhibitors and targeted therapy ( Combination therapy era) . I have witnessed even pre immunotherapy era when we used drugs such as Medroxyprogesterone acetate almost 30 years ago as the only hope in mRCC.

    Immunotherapy era - (IF-alpha ) and IL-2 were the only drugs used in those days . The SWOG trial and the paper by Robert Flinnigan (NCI trial )  and it's meta analysis had shown the  efficacy of IF-alpha along with CRN  as against CRN alone  ( 7 months survival benefit )  and  those days it was a common practice.  However in terms of efficacy, IL-2 had the best response, almost 20% cure rate in mRCC, but had a lot of side effects and  high morbidity /mortality and had to be given in ICU settings.

    Then came the drugs such as VEGFR inhibitors such as Sunitinib , Sorafenib  and later Pazopanib and Axitinib and a few more . We also had monoclonal antibodies like Bevasuzimob and mTOR inhibitors (Targeted therapy Era) . I must admit, these drugs were better than IF- alpha and we started seeing good measurable responses both clinically as well as radiologically. One thing the readers must note is that the majority of the drugs was effective for clear cell RCC and not for other subtypes of RCC, though some of these drugs did show some efficacy in papillary and other non clear cell histology.

    Which one of these drugs should one use in clinical practice? was a confusing yet common  phenomenon amongst  the practicing urologists when these drugs in targeted therapy era appeared.  In terms of Efficacy  Sunitinib is slightly better , while in terms of side effect profile Pazopanib /Axitinib are better . Costs are not that prohibitive, many companies like Novartis provide Pazo free if a patient completes one year of treatment and I have many patients surviving beyond that. In general the trend was to perform cytoreductive nephrectomy followed by TKIs   and only TKIs in very high volume biopsy proven mccRCC.  European Society of Medical Oncology ESMO -2020 and EUA 2020 give guidelines about which drugs should be used based on IMDC risk stratification, it is useful.

    The next phase came when medical oncologists started pushing for TKIs as frontline treatment, suggesting that it has almost equal or even better survival as against the combination of CRN and TKIs. The CARMENA trial was all about using Sunitinib alone in mRCC and almost suggesting that CRN is perhaps not needed. This created a huge controversy. I have given a few talks on What do we do  after the CARMENA trial ?  If one analyses the CARMENA trial, you will see many flaws. First of all it was a non inferiority trial, secondly it was done over 70 + institutions across Europe and many centers did recruit maybe 2-3 patients max. There were cross over’s in both arms (Sunitinib Vs Sunitinib + CRN) and selection criteria were not strictly followed.  Therefore friends, just don't go overboard and remember CRN still has a role to play.

    The balanced approach I think will be:  In a case of mccRCC assess the risk stratification, start with TKIs  ( Axitinib or Pazo or Sunitinib)   , see the treatment response after 6-8 weeks / two cycles. If the response is good, you may continue with the therapy and perform CRN at appropriate time. If there is a disease progression, then perhaps no therapy would work - neither TKIs nor CRN, the aim should be palliation. There is a trial which is going on which will soon tell the timing of CRN.

    Now that we have drugs like Pembro which have shown good efficacy, we are talking about a combination of TKIs and IO. My favourite lately has been the combo of Pembro and Axitinib , having said that Pembro is very, very expensive .

    The presentation of Tony Chourie at SUO 2020 , is all about these  upcoming new combination therapies and the trials . Yes we have some exciting future, but it's a long way to go till they come out with meaningful clinical results, else we will be ' fooled' by the trials like CARMENA.  Newer drugs like HIF inhibitors are also exciting.

    At the end, the majority of these drugs and trials have revolved around ccRCC. There are some promising drugs for papillary RCC too. The article on Genomics from Nature's reviews takes you through the entire journey of understanding these different subtypes of RCC , its generics and based on that the possible effective therapy in years to come , but again a long way to go .

    Last but not the least , please keep yourself up breast  with these drugs in mRCC , it's simple to use it , you may not have to depend on a medical oncologist all the time for their use unlike chemotherapy ( A brave statement  at the end of 2020 !!!) 



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