Category Archives: RCC Basics

Genetic Differences in Kidney Cancer? So What or What’s UP?

A few years back, I attended a kidney cancer conference with a highly eminent kidney cancer doctor.  He opened his talk by saying he was no longer treating kidney cancer!  The room was stunned, patients already wondering where to go for the next appointment when he finished his statement. “From now on, I will be treating cancers of the kidney.”

Not a small distinction, and a great way to confuse the patient and the newly diagnosed, but is critical.

Just because some growth lands in the kidney, that growth is not the same person to person, and even not from kidney to kidney in one person. In the link below, CURE magazine, May 5, 2017,  interviews Dr. Marston Linehan who expands upon the history and future of this work, which I have used as the basis for this report.  This research started in the 1980s, when doctors and researchers noted that some families were at greater risk l to develop some growths and tumor, some of which ‘landed’ in the kidney.  The early work defined that disease, Von Hippel Lindau hereditary cancer syndrome as to its genesis–an inherited mutational tendency in the VHL gene.

This research started in the 1980s, when doctors and researchers noted that some families were at greater risk l to develop some growths and tumor, some of which ‘landed’ in the kidney.  The early work defined that disease, Von Hippel Lindau hereditary cancer syndrome as to its genesis–an inherited mutational tendency in the VHL gene.  Given that clue, patients with kidney cancer but from this inherited tendency, most often had mutations in that same gene.  These were ‘sporadic’, out of the blue mutations, but that opened the door to treatment improvements.  About 90% of patients with the more common clear cell kidney cancer have a mutation in the VHL gene–but not due to any inherited tendency.  Much work has been done for these patients and less for those with the rarer cancers of the kidney.

AND…there are more inherited kidney cancers which also enlightened research.  One is PRCC, Papillary Renal Cell Carcinoma, defined in the 1990s.  The gene that drove this kidney cancer was MET, wh0se mutations make those patients “highly likely to develop bilateral, multifocal, Type I papillary kidney cancer,” per Dr. Marston Linehan of the National Cancer Institute.

Research is being done for these people, as well as those who are affected by the similar disease which is NOT inherited. There disease also comes from sporadic mutations, these from the same MET gene.  This work is critical, as the generally available treatments are not as effective with the rare RCCs.

Still another and challenging rare kidney cancer is HLRCC, or hereditary leiomyomatosis with renal cell carcinoma. Linehan says it is not uncommon, and can make the patient vulnerable to develop leiomyomas–particular kinds of growths–and an aggressive form of Type 2 papillary kidney cancer.  Quite different genes make this happen, which can be referred to as Krebs cyle enzyme mutation cancers.  Obviously, still quite different that the garden-variety clear cell RCC (ccRCC) and requiring quite a different approach as to treatment.

Though there are currently studies underway to find more appropriate therapies for these rarer forms of RCC, some with combinations of agents that have been developed earlier in the decade, and with agents that were not originally envisioned to be used with kidney cancer–oops, cancers of the kidney.

If you don’t really know the pathology of your tumor and its genetic drive, you don’t have a complete diagnosis.  And if you relatively young for kidney cancer, the 46 and under group, this is time to discuss it with your kidney cancer cancer of the kidney specialist.

PS According to Linehan, there are at least 13 different types of inherited kidney cancers, and at least 16 known genes that can cause cancer in the kidneys…lots to learn and to discuss with your doctors!





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Filed under genomics, Genomics & Genes, Newly Diagnosed, Rarer RCC Cancers, RCC Basics, Uncategorized

“Predicting Short Survival” article: A Self-fulfilling Prophecy for the Newly Diagnosed

I thought I had seen enough articles which concentrated on the stats of how poorly kidney cancer patients did, but then, this one came along from Norway.  “A Three-Variable Model Predicts Short Survival in Patients with Newly Diagnosed Metastatic Renal Cell Carcinoma”, just published in 2017, it is shocking and may create barriers to proper care for patients.  The title might have been more accurately titled something like, “How We Fail to Find Kidney Cancer, Therefore Dooming Many to an Unnecessarily Efficient Death”.

Maybe it especially bothers me, in that I have come to expect more of the several Scandinavian health system as I understood them. Also, that I am 1/4 Norwegian, it seems a personal affront.  To lay the ground work, I shall remind you that kidney cancer is often found in the ‘6th” decade of life, or in the 50s, 60s and 70s, most often.  (Any earlier, and there might be a genetic problem, by the way.)  But it is also slow-growing, often can do so without many overt symptoms, but there are often hints.  Of course, if you do not look for those symptoms and search out those causes, you get that slow-growing cancer to establish itself quite thoroughly!  You know the rest of the story, no doubt.

The facts are as follows.  Norway is generally sparsely populated, having about 5.2 million people, with an aging populations, with about 11% over age 70 at present.  There were about 814 cases of kidney cancer in 2014, and more to more, per the stats.  The background statement of the above study notes that it is “important to have realistic perspectives, especially if the expected prognosis is very unfavorable”.  Already I am wondering how expectations by the doctors affect the care they are about to give the newly diagnosed.

In one small area of Norway, Norland data was collected about all newly diagnosed patients, with the stated concern that in trying to select the “best treatment option for an individual, the poor prognosis groups is the most challenging one because aggressive approaches may result in serious side effects in these often frail patients.”  Thus, the researchers wanted to find out how those patients treated within the national guidelines failed.

A central measure of their expectations–no doubt built on the previous years’ patient responses–was the definition of “short survival”, i.e., after the initial diagnosis.  Short survival was for 3.5 months or less…yet the concern from above is in regard to the ‘serious side effects’ in these patients.  Dying within 3.5 months of diagnosis in a modern health care system seems a pretty serious side effect as well!  In this small area there were 48 patients identified in this recent study, 10 of whom died within 3,5 months.  Those 38 patients who lived four months or longer were deemed to have had long survival.  Obviously those patient who were doing badly at the time of diagnosis seemed to die  more quickly.  This seems at odds with the American experience, with much long general overall survival, but it is hard to get those stats, as the US measurements are in terms of YEARS of survival.  A metastatic kidney cancer patient is a Stage IV patient, with the 5 YEAR survival at 8%, per the American Cancer Society–whose stats are necessarily behind the times.  They modify that to note that low-risk patients have a 41% survival rate, intermediate risk patients have a 18% survival rate, and the high-risk patients have the 8% survival rate at five years.

Why such a difference?  The disease is similarly divided 2 to 1, male to female, and there is a near-similar mix of subtypes, such as clear cell, papillary and chromophobe.  The median age at time of diagnosis is 68, slightly higher than in the US. However, in the US, only about 30% of patients are found to be metastatic at time of diagnosis, but in this small study, 70% were found to be with metastatic disease upon diagnosis or within 3 month of that time.  Most important is to note that only 65% of patients in this study were given a nephrectomy, either full or partial.  And post diagnosis, only about 56% of those patients received any systemic treatment.

That seems enough to tell me that these patients were treated very differently that most US patients in terms of surgery, but other statistics were striking. Though the 60-69 age group represented 58% of the patients, only 3.3% were found under 60 years of age.  Was nobody looking for cancer in this group? Imaging for other diseases often reveals kidney cancer, so the 3.3% seemed off the statistical mark.

Only 30% were found to be in ECOG Performance status 0-1, with 70% already struggling with the effects of their disease. Another measure indicates that only 18% had good performance status.  This causes me to wonder how long those patients struggled as well to get a necessary imaging study to verify the presence of a kidney tumor.  (Only 65% of those got the darn things removed!)

Over 55% of all these patients had low hemoglobin, one of the simplest measures found in every blood test.  A pretty good clue that something very fundamental was amiss with these patients. In the group who died within the ‘short survival’ period of  three months, 50% of them had SKIN metastases.  Again, a very visible symptom, and hard to ignore when found with the low hemoglobin.

So how did they do in terms of median Overall Survival?  That was only 13.2 months, and with a 2 year survival rate of 40%.

Perhaps late to be diagnosed, with far fewer nephrectomies than in the US, and with far fewer systemic therapies applied post the time of diagnosis–no wonder the outcomes are so poor! Does this influence the doctor as he diagnoses a patient with low hemoglobin and some odd skin manifestations.  Does he recommend a nephrectomy–and how long does it take to get into such a surgery?  Does the likelihood of a poor outcome prevent the doctor from taking a more aggressive approach, not to recommend any systemic treatment for 43% of those patients? Does he just assume the patient will succumb very quickly to the disease!  Does that create the poorer outcomes in these patients?

A self-fulfilling prophecy is oddly reassuring to the party who makes the prediction, as he unwittingly works to make that prophecy come true.  Poor expectations for survival may well lead to that very outcome.  Wish it were otherwise.





Filed under Guidelines, Newly Diagnosed, Surgery

Kidney Tumors & Diagnosis? Size Matters–Big Surprise

Kidney cancer is generally a very silent disease. It is sneaky, hides out for years, and is often assumed to be something else.  In my case, my doctor essentially decided I was just a menopausal women with the ever-popular “stress” as a an extra.  The stress of carrying about a 10 cm tumor and wasting away  was probably part of it.

That slow diagnosis, often delayed for years is far too typical.  Only the greater use of CT scans has been significant in finding kidney cancer at an early stage. And just what is early or small? Looking for a cracked rib, or the dislocated shoulder has often revealed kidney cancer, and in the case of the shoulder, lung mets.  And then the hunt is on!  By the time this diagnosis is made, nearly 30-40% of kidney cancer is already metastatic.

The ‘classic triad’ of symptoms, are 1) blood in the urine, 2) flank pain, and 3) palpable mass in the abdomen. There are doctors who will consider kidney cancer only when the patient has these three symptoms, but that happens in fewer than 10% of patients.  The cancer has to be pretty far along to be found this way.  Meeting a pair of new doctors who were aware of my kidney cancer, they were obviously bewildered to hear that I had had none of the these symptoms.  “But those are the usual symptoms,” one said.  Maybe ‘classical’, but not ‘usual’.  Unfortunately that expectation is a barrier to good diagnosis.

Beyond the diagnosis and the staging of the disease is the pretty obvious question of what to do next. (Staging: another of those words used one way in English, and quite another in medicine No wonder we are confused.)  Getting treatment is derived from that ‘staging’.  To be told your cancer is at Stage I seems the only  bright spot of a cancer diagnosis,  but not so reassuring with kidney cancer.  The  “SMALL” Stage I kidney tumor is one which is confined to the kidney (good news) and is 7 centimeters or less.  Maybe Europeans react with the required, “Yipes!”, but few Americans would until they know that this is almost 3 inches in size!

Ain’t so small in my world, or in my kidney!, or anywhere else. In my previously-naive patient world, I thought a ‘small’ tumor was the size of a pea, or maybe a peanut.  In any case, these so-called small tumor are Stage I, of four Stages.  Don’t even ask about Stage V.  Calling a near-three inch tumor small reflects the history of many very large tumors being found in the early days.  Even in 1997 there was discussion about whether a 5cm (2 inch) tumor should be the ‘small’, and in the 1987 system, it had to be 2.5cm to be small, ie, about one inch a T1 stage.  I do not understand why this basic staging was so dramatically changed, but it may well be that there were so few truly small tumors found in this early CT era.

In any case, we now have a system which lumps all tumors 7 cm or smaller into TI category, re-divided into T1a if under 4cm, and T1b, up to 7cms.  This minimizes the sense of risk that comes with these larger Stage I tumors, despite clear evidence of much greater risk at about as they grow.  That shift to a more aggressive tumor, capable of having metastatic potential, seems to start just over 1 inch, about 2.8cm.  There is a measurable increase in risk of about 62% at this size, so waiting around for a mass to be palpable (ie, it can be felt) puts us all at risk.  And of course, that metastatic potential has likely started even earlier, prepping the body to accept new cancer in new locations.

Thus, the absolute need to monitor patients who have had large ‘small’ tumors far more carefully and for a longer time.  The reality is that even truly small tumors have the ability to start the metastatic process.  Tiny and invisible even to a CT, they can grow unnoticed for several years.  There is no magic ‘five years/safe at home’ for kidney cancer patients, sad to say.

So, if your doctor tells you not to worry, that he got it all, that it was small, that there is no need for further monitoring, you might just find another doctor who keeps up with the kidney cancer literature.  If you got this far with this post, you may be ahead of your doctor.

Re the above risk stats, see


Filed under Guidelines, Newly Diagnosed, Patient Engagement, Patient Resources, RCC Basics, Uncategorized, Your Role

Classifying Kidney Cancer by Its Biology; Good Looks Won’t Do It Anymore

Looks don’t matter in kidney cancer as much as they used to, as more information comes to us about the molecular or biological nature of the diseases which fall under the “kidney cancer” umbrella.  Can those important biological differences be seen in the pathology laboratory? Must we rely on next generation sequencing to determine which of the subtypes we might have?

Recent work by Dr. James Brugarolas and colleagues is reassuring.  Even as they found  new subtypes of clear cell renal cell carcinoma, they have also determined that these differences can be seen the pathology lab.

Why is this important?  So-called similar tumors may behave in quite different and more aggressive ways, so this is vital to understand the threat of recurrence from a very small tumor.  The affects monitoring and eventually will be helpful in drug selection.

An interview at the 13th International Kidney Cancer Symposium   October 2014

Cut and paste the above youtube address into your browser to be able to hear the lecture, while following along below.  The questions are in bold face.

Dr. James Brugarolas Discusses Biologically Classifying Kidney Cancer

“What we have learned with the development of next generation sequencing (NGS) is that no two tumors are the same. Every tumor has different mutations. Mutations are the drivers of tumor biology. With the advances of next generation sequencing, we have been able to identify and group different subtypes of kidney cancer, according to their mutation status.

Specifically, my laboratory discovered that the BAP1 gene is inactivated in 15% of clear-cell renal cell carcinomas. We found that BAP1 mutations are associated with high nuclear grade. That let us to hypothesize that patients who had BAP1 deficient tumors are going to have more aggressive tumors.

Furthermore, we found that mutations in BAP1 tended to anti-correlate with mutations in the second gene discovered by the Sanger Institute, by Michael Estrada and Andrew Futreal, the polybromo1 gene, PBRM1.

That led us to a classification that about 50% of the patients with clear-cell renal cell carcinoma will have PBRM1 deficient tumors and 15% of patients will have BAP1 deficient tumors. A small percentage of patients will have tumors that are deficient for both genes.

In a very productive collaboration we have had with Mayo Clinic, with Rick Joseph and Alex Parker, we’ve been able to determine that these different subtypes are associated with very different outcomes in patients. Patients that have tumors which are competent (not deficient) for both BAP1 and PBRM1 have excellent survival, whereas the cancer specific survival (CSS) is very poor in patients that have tumors that are deficient for both BAP1 and PBRM1. BAP1 deficient tumors have a somewhat intermediate survival phenotype, and the PBRM1 deficient tumors are similar to tumors that are competent for both BAP1 and PBRM1.

So we think for the first time, we’ve able to identify subtypes of clear-cell renal cell carcinoma that are likely to inform therapy in the future.

There is a gap between the discovery of the gene, to the determination of the clinical implications and subsequently to the therapeutic developments. That is because the therapeutic developments are going to emerge from the biologic understanding which we don’t have yet.

   How can improved classification of kidney cancer subtypes improve clinical trial design?

 That’s actually a very good question. So, what has traditionally happened is that a trial may be performed and one may find a group of patients–sometimes small, sometimes larger–that appear to do well with that agent. But if the group of patients is small, the trial is considered to be negative and the drug is abandoned. And I would say the problem is not that the drug did not have activity, it is that we were not able to identify the group of patients who appeared to benefit from that agent.

So the classification that we have developed and the identification of these different subtypes will pave the way to be able to do correlations. So then, when a clinical trial is executed when it is able to characterize better those subsets of patients that may benefit from the agent. For instance, as I was alluding to before, the BAP1 gene is inactivated in 15% of the tumors. It is possible that one of the drugs which has been tried in kidney cancer could have activity against that tumor. But there could never be a trial in that is positive that is being active in a small percentage of the patients, in 15% of the patients.

By identifying meaningful biological subtypes, we hope to deconvolute kidney cancer. It probably makes sense in trials going forward to do prespecified analysis of these genes that we now define as different biological subtypes–to be able to get at the question whether a particular treatment is having greater affect in one biological subtype versus the other. It is possible that it may not be that not all the PBRM1 deficient tumors that benefit, that are inhibited by a particular agent, there are other mutations. But it’s the beginning that which will lead us to identify those biomarkers and patients who are most resistant to a particular treatment.

 What is the significance of improved disease classification for kidney cancer patients?

 That is also an excellent question. These are discoveries that we and others have made over the last two or three years. The implications clinically have begun to be unraveled. It’s going to take significant effort and investment in research for us to go forward. We need to understand how loss of these genes, how mutations in BAP1 and PBRM1, are affecting processes inside the cancer cell, leading to kidney cancer development.

And in particular, we need to understand how BAP1, which is associated with most aggressive type of kidney cancer, is inducing that process. How is it that loss of the BAP1 gene makes the tumor be so aggressive? It’s only once we are able to elucidate the signaling pathways, that we will be able to identify targets for therapeutic invention.

On the other hand, we already know that for patients with localized disease, their prognosis is influenced biology of the tumor. I was alluding to this before, those patients who have removal of a tumor, localized to the kidney who deficient for BAP1 and PBRM1, they have a very high likelihood of recurrence in a short period of time. Those patients whose tumors are wild type for PBRM1 and BAP1 can do very well. (Wild type here means that the two genes are competent, or not deficient.)

Importantly, from the important view of translating these findings to the clinic, we have been able to develop assays, immunohistochemistry assays which are routinely performed in tumor samples at most institutions. (This is done in pathology labs).That allows us to very quickly determine whether we are dealing with the wild type tumor, BAP1 tumor, PBRM1 deficient tumor, or one that is deficient for both.

(Transcribed from the above YouTube video by Peggy Zuckerman. Any mistakes are mine alone, but hope this is helpful in understanding this approach to using gene sequencing in kidney cancer.

May 16, 2015)






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Filed under Genomics & Genes, Lectures from Experts, Medical Conferences, Rarer RCC Cancers, RCC Basics

Clear Cell RCC: Not as Clear as It Used to Be!

We struggle to understand what to do about our kidney cancer, but first must  exactly WHICH kidney cancer we have. Frankly, even the doctors are never too sure, and outcomes for patients with the “same” cancer varied widely.  No ready explanation was available, in those bad old days.

Treatment decisions were easy, but not effective for most, when every kidney cancer patient was treated the same.  Patients had surgery and were sent home. Those with smaller tumors, under about 2 inches, had little or no follow up.  Those with larger tumors might be monitored more frequently. Mets might emerge, and maybe more surgery would follow, but no meds were available until 1992 when high dose interleukin was approved.

Patients who presented with metastatic disease were not even offered surgery, being told that there no value to removing the primary!  An ongoing “controversy” was whether there was value in a nephrectomy when mets were found.  Too bad, so sad. (If your doctor is telling you that last bit, you need a new doctor. Now.)

Then came the recognition that there were different kidney cancers, variants and subtypes, all based on the look under the microscope.  Conventional kidney cancer became known at clear cell, and a mix of new subtypes were named.  We now hear of clear cell, papillary type I and type II, chromophobe and more.  Sarcomatoid RCC can arise from any of these types, confusing things and reflecting a more aggressive course for the patient.  Most are sporadic, out of the blue, but others have an inherited component.  Again, making things trickier yet!

Ironically, the trials in the late 80s of high dose interleukin which led to the first FDA-approved treatment, included all the above types. The relatively low response rate in this trial may have been due to the rarer RCC types, unlikely to respond.  This minimized the use of HD IL2, perhaps to the detriment of many patients. The targeted therapy studies often excluded the rarer types, hoping to boost response in a more limited group.  Few trials really test agents appropriate for the non-clear cell types, so the guessing game for them is really the norm.

With that background, there was still wide variation in the outcomes for clear cell RCC patients.  Some patients with small tumors, found at an early stage, can have very poor response to treatment.  Many such patients have long-term survival, easily over 10 years, while others who “seem” similar, succumb to their disease quickly.

Why is this the case?  Short term survival vs long term survival, aggressive appearance of mets vs slow-growing, good response to treatment vs minimal response?  Why would the same disease be so different?

Easy answer.  It is not the same disease.  Clear cell RCC, that so-called conventional type, maybe 75% of all the kidney cancers, is not really one disease. Clear cell may be subdivided into four separate types, each with its own survival pattern–and all due to its early genetic drivers. Researchers have been able to sort out the genes, compare the mutations, deficient or over-expressed, and find them in tumors of patients who were treated and followed over many years.

Just as there is no magic bullet, no one medicine that fixes everything, there also seems to be no one poison bullet.  It is not just one thing that goes wrong, one nasty gene breaking the DNA rules, but a combination.  And there will be more combinations.  This is like the typical disaster stories, where it is not just one thing that goes wrong, but a series of events and changes.  Each one of the series might not create a problem, but in combination and with the right timing, there is a perfect storm–the very aggressive tumor.

Without getting too technical, clear cell RCCs can have a mix of genes that mutate.  Recent studies have shown that two genes in particular, BAP1 and PBRM1 can either be sufficient (or competent or positive) or they can be deficient in their expression.  There are four possible combinations, positive for both genes BAP1 + and PBRM1+, negative for both genes BAP1- and PBRM-, and combinations with the BAP1+ and PBRM-, and the reverse, BAP- and PBRM+.

Why does this matter for the study patients? All of them had localized disease at the time they were diagnosed and all were clear cell patients of similar age.  BAP1 was mutated/inactivated/deficient in about 15% of these patients, and that mutation was associated with high nuclear grade, or a more aggressive type of tumor.

About 50% of clear cell patients had the PBRM1- tumors. Others had a mix of one gene positive and the other negative. Mutations of BAP1- and PBRM1- were rarely found together, but that combination predicted poor survival, in one study of just 2.1 years.   Having just the BAP1- had an overall survival of 4.6 years median, while the deficiency of PBRM1 (-) had an overall survival of 10.6 years.

This shows that clear cell RCC is really not one disease type, but four.  Most importantly for patients is the knowledge that these varying mutations may respond to different medications.  Also, these mutational differences can be seen in immunohistochemical or pathology tests, which can give greater guidance to treating physicians.

Coming soon is another lectures by Dr. Brugarolas, so watch this space.

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Filed under Genomics & Genes, Lectures from Experts, RCC Basics

Younger Patients & Kidney Cancer: Your Genes or Your Luck?

Once you reach a ‘certain’ age, you are horrified, but not surprised to get a cancer diagnosis, or hear about it in a loved one.  That same cancer in a young person is even more horrifying, we instinctively know.

Most kidney cancers (and there are more types than we previously knew) are found in people in their 60s and 70s.  Bad enough, but a cancer called by the same name and found in a younger person is often a very different cancer, with a very different prognosis.

Some new research recognizes that special attention should be paid to those RCCs found in patients 46 years of age and younger.  Why is this?

The quick answer is that this may represent a more aggressive kidney cancer and/or be of a familial or hereditary nature.  That important distinction has researchers strongly recommending that young patients be referred for genetic testing.  This can explain those special risks and create more appropriate treatment plans, and alert other family members as to special monitoring. Critically it may change the approach to any removal of the kidney and/or tumor.

Typically a small renal mass might be monitored or removed by either surgery or some laser ablation.  If removed, the tumor can be assessed by a pathologist–a look under the microscope.Without a prior biopsy, the ablated tumor will not be examined, and no genetic testing can be done.

BIG HOWEVER HERE: even with a good pathology report, that may tell only what that tumor looks like–not what pushed it to grow, i.e., the genetic drivers. And those genes don’t go away with the tumor, so the risk remains that more tumors will grow, maybe in the second kidney, or in the partially removed kidney.  Plus the rest that can happen with cancer…

An 75 year old whose small renal mass is removed will likely function well with one kidney.  That same tumor  in a 35 year old creates another challenge.  If that tumor is driven by familial genes–not just by sheer bad luck–more tumors on the other kidney may be in the works.  A partial nephrectomy   must be considered. The risk of more tumors emerging in that kidney AND the other kidney is high.  The younger patient needs decades of good kidney functioning, but those decades carry the risk of the emergence of more mets.

What else should trigger a genetic testing?

Quick answer: anything that doesn’t look like the senior  citizen with a single tumor in one kidney.  More officially below:

Early onset of kidney cancer is 46 years or less.

Bilateral (two-sided) or Multifocal (many locations) kidney tumors

Family history of kidney cancer, 1 or more close relative, 2 or more in more distant relatives

Kidney cancer with either a mix of other tumor types roughly related to kidney cancer or with lung cysts or pneumothorax (air leaking out of lung into chest cavity)

Personal or family history of kidney cancer syndromes.

The above list is from Yale  School of Medicine, Professor Brian Shuch, who work includes dealing with heredity forms of kidney cancer.

More small renal masses found at an earlier age in more patients, as our imaging techniques improve and more CTs scans are done. Not all will be hereditary, and many will be sporadic or out-of-the-blue kidney cancers.  Those are likely due to the sheer chance. Things go wrong as trillions of cells divide and make DNA mistakes along the way. Years of environmental damage may overwhelm the body’s ability to correct those DNA mistakes–i.e., the immune system gets overwhelmed, tricked, tired, etc.

Kidney cancer found at an early age or with the bilateral/multifocal tumors simply must be tested as to it genetic origins.  This gives information critical to protect the rest of the kidney(s) and to participate in treatment that is more helpful.  Finding an effective treatment will still be a challenge, but proper treatment requires knowing exactly which kidney cancer you have.  From there, a real plan can be developed.

Just as I remind all readers to work with an experienced RCC oncologist–not just a surgeon and/or urologist (sorry guys, we need a team)–those who fall into this early and hereditary renal cell carcinoma category must also work with super specialists.

The person to contact at NIH is genetic counselor Lindsay Middelton at (301) 402-7911. She is with the National Cancer Institute’s Urologic Oncology Branch.  An introductory link is below to the NCI and two other rare kidney cancer organizations.

Birt-Hogg-Dubé syndrome:

Other syndromes causing kidney cancer:




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Filed under Ablation & Radiation, Basics, Genomics & Genes, Making a Plan, Newly Diagnosed, Rarer RCC Cancers, Surgery, Uncategorized

Oligometastases?! Patients Changing the Rules

Kidney cancer is the focus here, but I can’t resist writing about the empowered and determined lung cancer patients who changed the rules–the NCCN guidelines–in treating their  cancer.  With this, there is  support for treatment for their newly established metastases which was previously lacking.  Translation for the patient was, “It’s come back, so just go home. End of story.”

What does this mean for kidney cancer patients, or for others?  For that matter what does “oligometastases” mean anyway?

” Oligometastases are defined as 1–5 distant metastases that can be treated by local therapy to achieve long-term survival or cure.”

Earlier, some doctors felt that there was no reason to treat a patient who was initially diagnosed with metastatic disease.  If the cancer had already metastasized, nothing that could be done, not even the removal of the primary tumor.  Oddly enough, patients often got no treatment and the self-fulfilling prophecy worked again.

We kidney cancer patients know better. (My 10cm tumor and the lungs full of mets would have NOT been treated by many doctors.)  Removal of the primary tumor can have real benefit, even when there is no treatment for the metastases.

Similarly, the emergence of mets post-surgery was also seen as a “game over” by many doctors.  The “got it all” surgery that was welcome news was suddenly a forgotten phrase. How many sad visits a year or two after of misplaced confidence? Kidney cancer will come back far too often, suddenly emerging near the old tumor or in some of the favored spots.  With kidney cancer, that is the lungs, bones, adrenal gland and the brain.

These new mets, generally in the area of the primary, are those oligomets.  Hard enough to say, and harder yet to be told that the docs will do nothing–because the guidelines say it is not worth it.  That was the situation for non-small cell lung cancer patients with new mets.

But these cancer patients were NOT having that kind of non-help!

They gathered all the data, showed the value of going after these mets and convinced the NCCN to make significant changes in their guidelines.  Now doctors and the insurance people cannot deny these treatments on the basis of these guidelines.

Patients helping patients, patients helping doctors, patients helping create better guidelines, patients living longer…might be a trend we can emulate.


Keep in mind that most doctors and insurance companies want to use treatment guidelines based on some acceptable medical standards.  One guideline comes from the National Comprehensive Cancer Network.  This establishes the working rules for what kind of treatment or monitoring is thought appropriate for any stage of cancer.  For example, the treatment for a Stage I tumor is quite different from that of a Stage IV tumor.  There are guidelines for shifting to new medications, and for monitoring of primary tumors or mets after surgery.

Since kidney cancer most often metastasizes to the lung, I monitor some of their sites, and was thrilled to see this.  Power to the patients, people!


Filed under Guidelines, Patient Activism, Patient Resources

Recurrence? Is There an App for That–or a Medicine?

Being diagnosed with kidney cancer is a stunner.  Facing surgery and endless, oft unanswered questions changes your life.  Patients with small tumors, easily removed, are often told not to worry about it coming back.  Of course, there is ALWAYS the possibility that even small “I got it all tumors” can recur.  Sadly, the current guidelines fail to catch about 30% of recurrences, using the 2013, 2014 guidelines.  These guidelines were from an earlier era, where there were fewer small tumors found, so there was data lacking on long-term follow-up.

We patients ask? “Why not just take the meds that the patients with metastatic disease do?  Wouldn’t that prevent it from coming back?  If it works to fight the mets, why wouldn’t it prevent new ones from getting a foothold? “

Why not use the meds that they use now against metastatic disease? Why wouldn’t that work?  Have they tested that idea?

In February of 2015, a study was released which comparing patient response to 1) sunitinib (Sutent),2) sorafenib (Nexavar), or 3) placebo (no real medicine).  This  three-arm study included 1,943 patients who had locally advanced clear cell and non-clear cell histology RCCs. They were thought to be at high-risk for recurrence of their cancer, and might benefit from “adjuvant” therapy.  The researchers hoped that they would see a 25% improvement in time to recurrence of disease with the meds vs no meds.. That would means that the typical 5.8 years median Disease Free Survival (DFS) would go to 7.7 years.

Sadly, there was no benefit to taking the active drugs compared to the placebo.  More sad is that the patients had side effects associated with the drug, referred to as “adverse events”. In fact, many dropped out of the active agent arms into the placebo arm, certainly knowing that the med they were taking were anti-cancer meds.  Those “adverse events”, severe fatigue, hypertension or hand-foot reactions, were observed in those taking the active agents and rarely in the placebo patients.

The median time on the drugs was 8 months.  That means half the patients  were on drugs more than 8 months and half were on the drugs less than 8 months.  Even those patients starting with lower doses of the drugs fared worse than the placebo group.

Despite taking the medications and enduring the side effects, the recurrence was about the same.   With medication or without, these patients, as groups, did the same.  Those taking the meds had Disease Free Survival of 5.6 or 5.7 years, similar to those not taking any real meds.  There was no real added benefit to these patients.  Certainly the quality of the life was affected by the side effects, and the constant reminder of the spectre of more cancer.

What can patients learn from this study?

The fear of recurrence is real. After all, the expected time until the disease progressed (love using that term for cancer!), was about 5 1/2 years.  These patients were carefully monitored with CTs on a regular basis, which caught their recurrences as soon as possible. Had they not been in this trial, it is reasonable to expect that many would not have received those scans and not know of the recurrence as it happened.

The reality is that the typical patient may or may not continue to be monitored. Even those who passed the 5 1/2 year mark without recurrence may not realize that RCC can come back.  Again, 30% of recurrences in small, non-metastatic disease are not caught.  One can assume that the higher risk group in this trial would also be at risk for that level of recurrence.

Take-home message: At present, nothing has been shown to prevent recurrence of this locally advanced disease. Even the non-metastatic small tumors that have sent out invisible “wanna-be mets”, and no one can yet guess who is at the most risk.

The best approach is to monitor yourself and your general health and to demand CT scans, especially in the lungs, where metastatic RCC is most likely to start.  That does NOT mean an x-ray, as those mets would have to be about 1/4″ in order to be seen.  My own lung mets were under that size when first found, but there were hundreds of them, and they grew quickly.  Not visible on an x-ray, but growing every day.

Despite the disappointing study above, the ASSURE study, more clinical trials are recruiting patients for similar studies using drugs that have already been shown to be less active than those in the ASSURE study.  I would be cautious in getting into such a trial, and would spend my energies seeing that my monitoring is extended at least until 10 years past my surgery–even with those “got it all” primary tumors.








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Filed under Clinical Trials, FDA Meds & Trials, Guidelines, Medications, Targeted Therapies, Uncategorized, Your Role

“Got It All!” or “Gotcha!” The Guessing Game…

No one wants to look for extra trouble after having been diagnosed with kidney cancer, even if the tumor is small.  Horrified already by the cancer, it is more horrifying to realize that there are no guarantees, even when told by a reassuring surgeon that he “got it all”.  The reality is that even small masses can have sent out cells to other sites, in the rest of the kidney, should it have remained, or to distant sites.  (In cancer, ‘distant’ is never as distant as it should be, as that means there is cancer in some area away from the primary tumor.  Could be lungs, bones or brain, sorry to say.) So now what do you do?  And what can you do?

With the more sensitive imaging techniques, x ray, ultrasound, CT scans, and MRIs, more smaller tumors are being found.  The hope is that finding and removing them will be completely curative, and there are plenty of papers to say that is the case.  But is it really true?  Unfortunately, finding tumors sooner also means that they may need to be “followed” or monitored longer than has been done in the past.

Consider the situation where a tumor about 2 inches in size is found, and scheduled to be monitored for five years.  Though with no symptoms, the patient gets that “last” scan, only to find a newly visible met. Not visible at the year four scan, it may have been slowly growing , unseen for 2-3 years  There may be further monitoring, and perhaps a surgery to remove it or one of the newer drugs is given, in hopes of downsizing or stabilizing the met. Happily the five year plan worked to catch this one.

Had that same tumor been found two years earlier, maybe just 1 inch in size, and monitored for five years, no further met would have been found.  The monitoring may well stop at five years, while the slow-growing met continues to grow, still not visible to the scan. It may only be symptoms at year 7 or 8 which brings the patient back to the doctor, and this time with larger and perhaps more mets, not visible at the year five.

Older monitoring schedules were based on the low and grim expectations for kidney cancer patients. There was little thought to tracking patients for more than five years. After five years there weren’t that many patients!

With earlier detection, and more treatment options, now is the time to review monitoring to capture recurrent disease, which we patient call, “It came back.”

We do look to the five year mark, thrilled to have made it, especially so if we have been cancer-free. Not quite like graduation, but more like the beginning of summer vacation.  But we (and our doctors) must be reminded to keep checking back in with the school principal/CT scan. We need to be sure no leftover bunch of cancer cells have become a measurable metastasis.

Let’s talk about size, as it really matters.  So does the attitude–aggressive or indolent–of the cells of  even the tiniest tumors.  Some may well have sent out their own colonists, looking for areas to set up housekeeping.  Clear cell RCC most often goes to the lungs, so lungs deserve close attention. X-rays can only see a pea-sized met, about 1 centimeter in size, so a CT scan, with and without contrast is best to find new mets.

What are the chances of finding mets, either sooner or later, with a small renal mass?  Lots of stats and some terminology here, so take notes as needed. Better yet,  grab your own post-surgery report, or the imaging reports so you know where you stand.

Measuring Small Renal Masses

Primary kidney tumors are measured on a T (for primary Tumor) scale that runs from TX–no primary tumor found, to T4, which is any tumor 10cm or larger(There are 2.54cm to the inch, so that is 10cm/2.54cm=3.9 inches.  Think four inches, and remember that it can be shaped like a potato, not a ball or a pancake. They can be measured  at a different spots in different scans. That is why measurements can vary from report to report.

T1 tumors are divided into T1a and T1b, and are limited to the kidney.  T1a tumors can be up to 4cm in size, using the largest dimension. Officially this is the small renal mass. Volume counts in the real world, but a 4cm x  2cm will be described as the same size as a 4cm x 4cm tumor.

Tumors which are named at T1b size are still limited to the tumor, but can be up to 7cm in the longest dimension, so about 2 3/4 inches long. The officially small renal masses   No longer described as small, it SOUNDS small by the name.  Assuming that there is no other evidence of cancer outside these masses, this is Stage I cancer. Given the grade of the biopsied tumor, it may be considered to be low or high grade, which is a measure of the aggressive nature of the tumor.

Tumors in the T2 range are also divided into T2a and T2b.  These are still limited to the kidney, with the division at the 7cm mark. T2a tumors are over 7 centimeters (think 3+ inches), and up to  10 centimeters, nearly 4 inches









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Filed under Guidelines, RCC Basics

My Radiologist or New Best Friend

In our kidney cancer world, it is unusual even to know the name of the radiologist, and most patients rely on his report, as given to the doctor. Many kidney cancers are “incidental findings” on CTs given with another diagnosis anticipated, broken rib, for example. Thus, it is the radiologist who recognizes the cancer long before either the doctor or patient. It may be a metastases that is found, with the primary tumor not yet imaged, or vice versa. If the tumor is relatively small, and no mets are seen in that initial scan, most patients are assumed to have localized disease. Often there are sudden plans for surgery, but not necessarily to search for other distant mets. The patient may be told, “I got it all.”

Of course, that is the best news, and the only news we want to hear.  But we are wrong, as what we NEED to know, even before the surgery, is whether or not there has been a spread of the cancer.  Treating kidney cancer is already a guessing game, and without knowing the whole game and all its rules, the patient is too often the loser. (Look for a longer, somewhat geeky post on small primary tumors and their potential to metastasize, both quickly and years later.  Ain’t a pretty picture.)

Any good radiologist will know that even small primary tumors can have already produced distant mets. That radiologist likely knows  that additional imaging should be done in such cases. The GP or even the urologist without RCC experience may NOT know that.

Too often small, overlooked mets in the lungs or on a bone can go unnoticed for months or years. Only the radiologist can provide a complete understanding of the extent of the cancer, and only with imaging outside the area of the “incidental finding”. He is the first line of defense, and often the first real expert in determining the extent of the disease. Thanks to those unsung heroes!


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Filed under Ablation & Radiation, RCC Basics