Monday, August 24, 2009

Prostate cancer - Part 2

This is a follow-up from our August 10th post. If you missed it, start here.

Normally Grant writes about a topic from his 23andMe report, followed by commentary from two healthcare providers, Marc Williams and Janet Williams (who happened to be related by marriage - to each other). For this post we reverse the order.

Perspective from a Certified Genetic Counselor

As someone who works with individuals who are seeking risk assessment for familial cancer, Grant’s result is really frustrating. What in the world does he do with this information?

He can remain nonchalant, nonplussed, implacable: “don’t worry, be happy”. He can go to his doctor and discuss this result. The provider may or may not think this information merits consideration in decisions about screening. Should it merit consideration? He can be screened with an exam and a PSA.

Grant is now in the position of “waiting” for prostate cancer.

PSA Screening + Genomic data = Prostate Biopsy

It doesn’t help that the most publicized story about genomics and prostate cancer (Jerry Gulcher) involves a fellow who is intimately involved with genomic testing. He saved his life by insisting on a prostate biopsy despite a normal PSA. It is difficult to keep any perspective when a story comes out that is so compelling! There is probably much more to his story, but it the short version that gets referenced.

The 23andMe result information that Grant now knows may provoke him to seek screening. However, he has no assurances that screening will be anymore sensitive because he is known to have markers found in men with prostate cancer. As recently demonstrated, PSA levels are not consistently sensitive to the presence of prostate cancer. PSA levels can be normal in individuals with advanced prostate cancer. High PSA levels are not caused solely by prostate cancer. Digital rectal exam can reveal nodules or an enlarged prostate, but either can be a benign finding. The presence of the risk markers cannot predict if a high PSA is more likely to be prostate cancer. The markers do not imply reassurance that a normal PSA level rules out prostate cancer. The high-risk markers are not correlated with aggressiveness of prostate cancer or its ability to metastasize.

The Clinical Decision Conundrum

The nightmare situation that Grant may not have considered is how this information now shapes the decisions he makes from here on out. For Grant, not acknowledging the risk information would be ironic. He is in the business of incorporating genomic information into medical records and medical care. He believes in the future of genomics and personalized medicine. The current reality is that the evidence to use the information gained in genomic testing does not facilitate the ability to take specific action. In addition, the screening we currently use to detect prostate cancer is itself flawed in its ability to adequately identify men with prostate cancer. We use the test because it is all we have at the current time.

Grant is caught between a rock and hard place. He can use his genomic result to direct screening tests with results that are “fuzzy”. The screening tests may indicate risk or suspicion of prostate cancer, but not disease. Prostate cancer can only be diagnosed with biopsy. What is Grant’s threshold for prostate biopsy at this time? How will his provider be able to discuss sound options when there is no evidence to guide a decision (not that that has stopped medicine in the past). I am angry that he now has information that indicates an association with increased risk for cancer, but with no way to apply the information in a way that can prevent or alter the development of prostate cancer. What decisions will Grant make differently because he and his provider now know that he is at increased risk?

Job Security

Finally, I am concerned about those who do not have Grant’s laissez-faire attitude about increased risk and cancer. Perception of risk and communicating risk with some perspective is tricky business. I think 23andMe has worked hard to provide ways to visualize and explain the quantity of risk. The complexity of risk and personal reaction to risk - really an “incorporation” of risk into one’s concept of self - is not explored. The upshot is that it may mean job security for me and other genetic counselors.

Grant's Comments

This is great. I’m getting free genetic counseling to help interpret my 23andMe report. Not having a medical professional guide a patient through genetic test results is a common criticism of direct-to-consumer (DTC) testing services. I’m lucky. With Janet, I have that issue covered.

Here Comes My Excuses

At this point, I haven’t approached any clinician with my 23andMe information. This includes not talking with a doctor about my prostate cancer risk. Janet has certainly given me a lot to think about. In contemplating my reaction (or lack thereof), I think it comes down to the fact that, from the information I have now (my current and possibly changing genetic risk, my lack of family history, and my age), I don’t have any alarm bells going off in my head.

I have learned a lot about PSA screening – and how it is not always useful – both from Janet and from my own research on the Web. One of the arguments against DTC testing is that its clinical utility has not been proven. I find this very ironic in light of a critical point Janet made in her post. “The current reality is that the evidence to use the information gained in genomic testing does not facilitate the ability to take specific action. In addition, the screening we currently use to detect prostate cancer is itself flawed in its ability to adequately identify men with prostate cancer. We use the test because it is all we have at the current time.”

Warning. Editorial comment to follow. Sometimes the anti-DTC voices do not use the same standard for personal genomics that they do for currently accepted medical practices which also have limited proven utility. In other words, we should not ban DTC testing because of its early stage and many questions concerning its clinical value, just as we will not stop using other sanctioned but vulnerable clinical tests. Interestingly though, results of a survey on awareness of personal genomic testing that I refer to in a following paragraph show some evidence of limited clinical utility. (End of editorial comment.)

A Link Between Prostate and Colorectal Cancer

I learned from the 23andMe website that “three SNPs in the same area of the genome have recently been found to be independently associated with prostate cancer risk. This region is called 8q24, because it lies within band 24 on the long arm (named the "q" arm) of chromosome 8. The three SNPs are not close to known genes (although there are others located farther away).” I then discovered this week from the website that both prostate and colorectal cancer have suspected risk-causing SNPs in the 8q24 region. 23andMe tells me about a published study on this subject titled “A common genetic risk factor for colorectal and prostate cancer.”

Although not ready for primetime, 23andMe does include data targeted at my risk for colorectal cancer. This information is listed under their Research Report section in the ‘Elevated Risk’ category. As stated by 23andMe, “Research Reports give you information from research that has not yet gained enough scientific consensus to be included in our Clinical Reports.”

click to enlarge image

The Issue of Risk

One of Janet's main concerns with DTC personal genomic services is the communication with and understanding of risk by the consumer. She states that “the complexity of risk and personal reaction to risk - really an “incorporation” of risk into one’s concept of self - is not explored.” An excellent discussion of this topic can be found on the UK’s PHG Foundation website. They have an article titled "Understanding DTC genetic risk prediction services" that points out that "because the calculated risk is updated every time a new association is discovered, the prediction for an individual can change from being above average risk to below average risk overnight. This is particularly problematic where it might result in opposing recommendations". The article concludes by saying "companies offering genome-wide risk prediction services should ensure that their customers understand that, whilst the measurement of the DNA sequence itself (the assay) will remain constant, the interpretation of the result (the test) is likely to change as the science develops".

Let me quote Janet one last time. She writes "the presence of the risk markers cannot predict if a high PSA is more likely to be prostate cancer. The markers do not imply reassurance that a normal PSA level rules out prostate cancer. The high-risk markers are not correlated with aggressiveness of prostate cancer or its ability to metastasize". I found these three sentences made the most impact on me.

Wow. We sure have a lot more research to do.

Awareness of Personal Genomic Tests

Also from the PHG Foundation website is an article on a study surveying both consumer and healthcare provider knowledge of personal genomics during the year 2008. On the consumer side, of 5,399 respondents, 22% were aware of personal genomic (or direct-to-consumer) tests, 0.3% had used these tests, and two-thirds of these users had shared the test results with a healthcare provider. That would be 2 out of every 1000 patients - certainly not enough for doctors to complain about yet.

I found the medical professional survey results really surprising. The 1,880 physician respondents (mostly family physicians, internists, pediatricians, and obstetrician/gynecologists), only 42% were aware of personal genomic tests. Among those aware, 42% had at least one patient who asked questions in the past year about having such a test, and 15% had at least one patient who brought the results of a personal genomic test to them for discussion in the past year. The biggest discovery according to the study was, “among the latter group, which is composed primarily of internists and family physicians, 75% indicated that the personal genomic test results changed some aspect of the patient’s care, such as screening tests offered, medications or dosages prescribed, lifestyle changes recommended, frequency of follow-up appointments, or diagnoses made.” (Emphasis added of course.)

Getting back to me

Janet is right. It would be a bit embarrassing if I couldn’t make wise decisions related to how I use my 23andMe report since I work in the clinical genomics industry. Should I schedule a prostate cancer screening? The pressure is on.

Read the next post - I Want A New Drug - One That Matches My Genotype


  1. I have a question for Janet Williams:

    If, as you suggest, the difficulties related to accurate risk assessment are as complicated as you have intimated,what would you suggest that Grant should do? Also, may I ask what your personal opinion is of direct to consumer testing options?

  2. A RESPONSE FROM JANET (just posted by Grant)-

    I don't have a specific recommendation for Grant for several reasons. First, I am not a physician and do not order tests, interpret PSAs or manage patients for general health screening such as prostate cancer screening. I outlined for Grant the types of decisions he will need to make, i.e. initiating prostate cancer screening now rather in when he turns 50. I really can't interpret a course of action for Grant, with or without his 23andMe result, because that is not in my scope of practice.

    As for direct-to-consumer, DTC, testing, I am not entirely against such opportunities, but I am cautious and concerned about the use and impact of information before we know we know even fndamentals about the applicability for an individual who is different (e.g. no cancer) than the research group (e.g. has prostate cancer). I am also concerned because test results are complicated and context for the result explanation makes all the difference in the world. Consumers who participate in DTC may not know what they don't know. Yes that happens all the time, but that doesn't make it a good model for health education and health management.

  3. Ms. Williams,

    Thank you for your response to my questions. I have personally never had to see a genetic counselor for risk assessment, but I am considering doing so in light of some medical information I recently received.

    To be honest, my primary concern related to DTC testing is simply that I am not sure private information is kept confidential by companies such as 23andMe. I read Dr. Williams' post on the disclosure documents from 23andMe, which didn't make me feel any less concerned.

    Who governs these private suppliers? And does anyone other than the company benefit from their research?

    This line of thought brings a number of questions up to the surface for me.

  4. I've been looking at the last posts, and it's interesting, because if you really step back from what everyone is talking about, nobody really has much idea at all about what the data produced by DTC actually means, do they? It's back to Marc's original answer to the questions I posed at the very beginning, which is that the community of experts really hasn't emerged or solidified at all yet, and consequently there can be no independent consensus on what anything means on the ground where the patients are. And in the case of prostate cancer, if you combine that uncertainty with the unreliability of PSA testing as an exclusive marker, the Gulcher case, etc., it looks to me like you're left with a lot of biopsies and a bunch of oddly shaped question marks floating around in the air with nowhere to land.

    And yet, per Grant's statement at the end of his post, 75% of doctors who participated in the one study who got genomic or genetic data changed something in their patient’s program of care because of the information. That sounds kind of dodgy to me, given the fact that the meaning of the basic data hasn't really been validated according to any generally recognized consensus. Janet is very honest about saying that she really doesn't know, even from her highly expert perspective, what that information means for patients in any general way. I can see the utility and importance of her role in working with individuals and their specific challenges, but she's refreshingly candid, as was Marc, about the fact that nobody really knows what the hell is going on beyond that. It really all needs to stay in the oven just a bit longer, doesn't it?

  5. A RESPONSE FROM JANET (posted by Grant)

    I think that you are right to be concerned. There is no regulation that governs this testing process or results information. The privacy protections in place for your health data in medical records is clearly outlined in federal legislation. The testing process, the results and implications that are generated in DTC testing are not subject to the privacy laws enacted with HIPAA regulations. The research partners that have contracted with 23andMe are not specifically listed in the agreement signed when a person has genomic testing through 23andMe. You have no choice to participate or which researchers can have access to your DNA information. If you wish to have 23andMe testing then you also agree to participate in research (this is how I understand the agreement. Marc may be able to address that with more clarity.)

    I imagine that the researchers who have contracted with 23andMe hope to profit from the genomic data supplied as a result of the interaction. This does not necessarily mean that the research partners will have direct contact with you or have identification information that directly ties your name to your DNA result. Most of us do have concerns that de-identified information is still a series of steps or a code away from being linked with identifiers.

  6. ya it usually happened because there are no proper system of scanning and diagnostic center. the cancer become more common due to the elimination of the boundaries so we must set some boundaries and follow that if we desire to safe the community...