Posts Tagged ‘Prostate Cancer’

Cancer screening Part 2: what works?

Sunday, August 11th, 2013

A blog post in The New York Times online recently addressed this issue noting, "Definition of Cancer Should Be Tightened, Scientists Say."

Here's a typical scenario: We've had a screening test for some form of the illness many of us fear the most (actually, I fear Alzheimer Disease at least as much). Then we hear the words, the really scary ones. "You've got cancer." We may not hear the modifiers that come before the C word, or anything else that follows. The National Cancer Institute's (NCI) working group wants to clarify that some conditions are pre-malignant (they're not cancer yet and, in certain cases, may never become carcinomas {another term for cancer}).

I want to return to the JAMA preprint article  I mentioned in my last post; it's titled "Overdiagnosis and Overtreatment in Cancer? An Opportunity for Improvement"

The group focused on cancer screening to include breast, lung, thyroid, colon, cervix, melanoma and prostate exams.  They tracked the incidence of a variety of cancers over the thirty-five-year period from 1975 to 2010 and found three different result patterns have been noted as more and more of us are screened for more and more conditions.

Some cancers have been diagnosed somewhat more frequently, but in many cases are less serious variants, less likely to kill us, so, overall, they are causing fewer deaths. Other malignancies are being found less frequently (due to improved and/or more frequent screening resulting in precancerous stages being treated) and the death rate from them has gone down considerably. And some cancers are being diagnosed much more often, but much of that increment is what the researchers termed "indolent disease," less active or progressive disease and overall their death rate is nearly unchanged or increased much less than the percentage change of their being diagnosed would indicate.

Let's take cancer of the prostate for an example of the first group. The incidence (rate of occurrence) in cases per 100,000 men has gone from 94 to 145.12, a fifty-four percent increase, while the death rate from the disease has gone down 30%.

So we're doing better with treating this form of cancer, seeing a lower mortality rate, but we're discovering considerably more cases that are not causing deaths. As I said in my last post, I've decided not to have any more PSA tests; at my age (72), other things are much more likely to kill me than prostate cancer. I clearly would have made the opposite choice (and did) at age 45 or 55.

Mammograms can save lives; they also can find pre-malignant lesions.

Mammograms can save lives; they also can find pre-malignant lesions.

The other tumor in the first group is breast cancer. Mammography has certainly become more of a routine procedure looking for breast lumps, but while the incidence of breast lesions has gone up 20% in the thirty-five year interval the NCI group looked at, the death rate has fallen by 30%. Much of that is due to what is termed adjuvant therapy, e.g., chemotherapy following surgery.

But another group of women with a positive mammogram have a less serious form of disease called ductal carcinoma in situ. The NCI webpage on this tumor says it is noninvasive, but some (uncertain) percentage of these can progress to an invasive form.

What is DCIS? It's the most common type of non-invasive breast cancer, starts in the milk Ducts, has been termed a Carcinoma and is In Situ which means "in its original place."

The NCI group who published the JAMA article terms it a premalignant condition and would prefer it not be called a carcinoma. Most of these lesions are small (~70% are less than 1 cm in size) and 80% are not found by breast examination, but show up on a mammogram.

Another NCI group, however, reviewed the medical literature on DCIS saying until recently the usual response to its discovery was a mastectomy. More recently there have been two randomized, controlled trials of breast-conserving surgery (lumpectomy) combined with radiation therapy and even more recently a double-blind prospective trial utilizing chemotherapy with the drug tamoxifen given daily for 5 years in addition to lumpectomy and radiation.

A control group had the surgery and radiation plus a placebo. The group that got tamoxifen did considerably better and other clinical trials are in progress.

The second group of tumors included colon cancer and cervical cancer. The statistics are fascinating. For colon cancer the incidence rate has gone down 31% and the death rate 45% and the trend is quite similar for cancer of the cervix (5 and 59% decrements)

We all have a colon, so let me focus on that cancer for a moment with a recent personal vignette.

My father had a large sessile polyp, a projecting growth without a stalk, in the very first part of his colon. It was initially benign, would have been difficult to remove and he was in his late 70s. so it was repeatedly observed and biopsied. Eventually it had a superficial layer that was cancerous. By then he was nearly ninety and the decision was to shave off layers until what was left was benign.

So that gives me a positive family history of colon cancer.

My previous colonoscopy (2006) was totally negative and without that family history my gastroenterologist would have said, "Come back in ten years."

Some colon polyps are relatively easy to remove.

Some colon polyps are relatively easy to remove.

Because of Dad's polyp, my GI doc wanted me back in seven years. And he was right; this time I had three small polyps, all of them benign and all on stalks (The technical term is pedunculated.), making them easy to snip off. I had decided to stay awake and watch and the procedure, while somewhat uncomfortable, was fascinating. I went home reasonably confident that my polyps were benign.

But there are three kinds of those colon polyps, according to the followup letter I received. Type one is of "minimal clinical significance." Type two, which I had, is benign, but potentially precancerous. Early colon cancer screening for first-degree relatives is recommended. It was suggested I speak to parent (both dead), siblings (my only sib died at fifty-seven) and children (my daughter), so they can discuss colon cancer screening with their physician.

I copied the letter to bring to my daughter on a vacation trip we're taking.

Type three is also benign, but there's considerably more chance of it turning into a cancer.

So my next colonoscopy will be in five years this time.

If I had a totally normal colon at age 72, my GI doc had said he'd not suggest any more colonoscopies ever. My routine ten-year-interval next one would have been at age eighty-two and that, he felt, is too old to screen someone whose seventy-two-year-old colon was negative for any polyps.

But with their natural history of being potentially precancerous, the discovery of types two or three leads to a change in schedule and a family search is quite reasonable.

And, I take it, that's why the incidence of colon cancer and the death rate from that malignancy have gone down over that thirty-five-year period. There's presumably been better treatments developed for those who do end up with that form of cancer, but by dong colonoscopies and removing pre-cancerous lesions (i.e., polyps), we're preventing many of them from altering into malignant tumors.

So those are examples of the group of tumors that are being discovered more often, but are causing fewer deaths and of one (colon cancer) that our screening is helping prevent.

I'll write about cancer of the cervix and of thyroid cancer and melanomas next time.




Cancer Screening Part one: Incidentalomas & PSA

Monday, August 5th, 2013

I was reading the New York Times online today and noticed an important article in the Health section. A working group from the National Cancer Institute (NCI) had just published an article in the pre-print edition of JAMA that will likely change a highly significant face of medicine for many of us.

The issue is cancer diagnosis and, in many cases, over-diagnosis. Some pre-malignant conditions, in the viewpoint of this distinguished group, now come with the word cancer attached. That may lead to extensive testing, surgery or chemotherapy (or radiation therapy) and much mental anguish (and potential physical harm) for the patient involved.

Abnormalities, potentially malignant, can be discovered while scanning or even examining for something else. Dr. Peter Libby, chief of cardiovascular medicine at Brigham and Woman's Hospital in Boston, a Harvard medical school teaching facility, wrote a June 8, 2010 piece in The New York Times titled "The 'Incidentaloma' Problem with Medical Scans." A columnist for that paper had a CT scan for other reasons; a kidney mass was detected and a three-hour operation and eventually a six-inch scar ensued, yet the mass was benign. Dr. Libby's review of the medical literature with his area of expertise in mind showed that greater than eight percent of cardiovascular imaging studies revealed incidental findings that led to further medical procedures.

His conclusion was we're doing far too many CT scans.

Another physician wrote an April, 2011 piece in US News and World Report about a woman referred to him as a followup of an ER visit for abdominal pain that turned out to be viral gastritis. She too had a CT scan which showed her liver and intestines were normal, but one of her kidneys had a tiny mass, almost certainly a benign cyst. But the radiologist, while noting this lesion had all the features of something non-cancerous, covered his or her behind by saying, "Cannot rule out malignancy. Clinical correlation required." Translation: it was almost certainly nothing serious, but there was a very small chance that it might be cancer, and now it was the surgeon's job to make sure it wasn't.

But it's not just those advanced radiologic procedures, or MRIs or other tests; It's the mentality involved and that includes physical exams.

Let me give you a personal vignette. In 1969, as a second year clinical fellow in Nephrology, I went to see the Chief of Urology because of an abnormal lab test that involved my kidney function. A few questions later, he determined it was due to a diet I was on for a research project.

"But as long as you're here, Peter," he said, "I'll check your prostate."

It wasn't quite normal, a tad bigger than it should have been. He said, "You'll have a TURP (transurtheral resection of the prostate) by the time you're sixty"

He recommended I monitor my symptoms (I had none at the time) and get repeat examinations at intervals.

Well, I'm seventy-two and haven't had that surgical procedure. But what I did have, for many years, was a yearly digital prostate exam and, after 1994, a PSA (prostate specific antigen) blood test done periodically. At some point not only was the gland enlarged, but it the urologist involved thought it was also slightly asymmetric, so I had multiple biopsies, even though my PSA had consistently been less than 1.0, e.g., way below the level of concern.

All those biopsies showed benign (non-cancerous) tissue.

Now that I'm over seventy I don't ask for a PSA test, wouldn't agree with one if it were suggested and had my last digital exam of the gland several years ago.

But if I had that cancer at age 28 or 40, I would have been in real trouble. I would have been concerned about a malignancy that would likely kill me and would have welcomed any logical treatment for the disease. The NCI webpage on prostate cancer estimates nearly 240,000 new cases will be diagnosed in the United States this year and almost 30,000 men will die from that disease.

But the natural history of the tumor in most older men (>70 years old) is such that they will most likely die from something else (e.g., heart disease).

The NCI's fact sheet on the PSA test is well worth reading. An initial statement is that the higher a man's PSA level is, the more likely he has cancer of the prostate. Then the caveats begin: there are other reasons for the PSA to be elevated (I now have one of those, BPH or benign prostatic hypertrophy, an enlarged prostate). Half of all men over the age of fifty have BPH that is symptomatic with some hesitancy in starting their urine stream and/or a smaller stream.

If I had actually had cancer of the prostate at age sixty, my PSA may have been elevated. Then I would likely have had surgery to remove the tumor if it was localized to the gland and my physicians would then have periodically repeated my PSA testing to monitor if I had a recurrence of the neoplasm (a new and abnormal growth of tissue in some part of the body, especially as a characteristic of cancer).

A PSA level under 4.0 (nanograms/mililiter) was considered to be normal (my last PSA, done three years ago, was 0.7 ng/mL). In the past, if a man had a PSA level above 4.0 his physician  would have likely suggested biopsy to see if he had prostate cancer. But there are men who have that malignancy and yet have a PSA under 4.0 and, as I mentioned above, other, benign conditions can elevate the PSAwhile some medications used for BPH can lead to a lower PSA level. Only a quarter of those guys who have a prostate biopsy because of a PSA that's elevated actually have cancer of the gland.

But now there's considerable question whether PSA testing should be a routine, even though medicare and many private medical insurance plans cover a yearly screening using this test. The consensus seems to be that men should hear the pros and cons of the test before giving consent for it to be performed.

If 1,000 men in the 55 to 69 age range get screened with this test every one to four years, 100-200 will have false-positive results (no cancer, but an elevated PSA) and may have a biopsy recommended and, of course, worry about what's going on with their prostate.

One hundred ten, according to the website, will be diagnosed as having prostate cancer and nearly half of those will have treatment complications (The National Cancer Institute website mentions sexual dysfunction, bowel or bladder control issues and infections.)

Four to five will actually die from prostate cancer, but five of every 1,000 who don't have the screening will die from that cancer.

So the net is 1,000 have been screened to save 0-1 life.

And to further complicate things, the research done to determine what the normal upper limit of PSA is has largely been done in white men only.

So where do we go from here? There are studies being done to look at precursors of PSA, rate of change of PSA. free versus bound PSA etc.

We need  a better method to tell us if a man has a cancer or a benign prostate condition and to determine which prostate cancers are highly malignant fromt hose that are slow growing.

And all that's just one cancer-screening tool.


My prostate and yours: benign and malignant

Wednesday, April 10th, 2013
At my age, I'm not scheduling this.

At my age, I'm not scheduling this.

I just printed an article from the Annals of Internal Medicine that confirms my own leanings toward prostate screening tests. In one of my old posts I told the story of having an abnormal blood test for kidney function and seeking out our senior urologist at Duke. I was a clinical Nephrology fellow at the time and when I was seen, the Chief of Urology asked what kind of diet I was on.

I groaned at that point since I realized I was in the middle of a research project and eating a very high-protein diet. That's why the more accurate of the two blood chemistry tests was entirely normal and the other, clearly influenced by my diet, was high.

He then said, "As long as you're here, Peter, let me check your prostate.

The digital rectal exam (DRE) revealed I had a mildly enlarged gland for my age and the urologist said, "You're going to have a TURP by the time you're sixty.

I knew a TURP was a transurethral resection of the prostate. If you look at the Mayo Clinic website I've provided, you'll see it's a procedure to relieve partial obstruction of the urethra, the tube that runs from the bladder through the penis to allow normal urination. The prostate itself, whose major task is to provide seminal (sperm-carrying) fluid, is a walnut-shaped, one ounce gland, or at least it is in younger men. As men age the prostate commonly enlarges. If it does so in a non-cancerous way, the condition is called BPH, benign prostatic hyperplasia (or hypertrophy as I was taught in medical school; the first term implies more cells; the other a bigger gland without specifying how it got that way).

As the prostate gets bigger and partially blocks the outflow of urine, men have a decreased urine stream, difficulty starting its flow, dribbling after urination or a more frequent need to pee, especially at night.

Urologists do about 150,000 TURPs a year in America, although there are a number of other procedures to treat BPH. And they want to do a DRE and draw blood for a PSA on more of us guys than I would agree with. There are other tests in their repertoire: rectal ultrasound, urine flow study and cystoscopy (inserting an instrument into the urethral to actually look at how narrow the passageway is).

The American Urological Association's (AUA) webpage on the surgical management of the condition says 88% of men who have a TURP will have significant improvement in their symptoms. But there are lots of complications that can occur right after the procedure: infection in 15%, bleeding requiring blood transfusion in 5-10%, impotence in 14%, incontinence in 1%. Ten percent may require a second operation within 5 years.

There also are medical therapies for BPH; I take two different pills a day for my BPH and will turn 72 in two weeks. I haven't needed a TURP yet.

But that's benign disease: how about prostatic cancer?

The ACP says there's debate on screening; what does your physician think?

The ACP says prostate cancer screening should be individualized; what does your physician think?

The recent Annals article I mentioned looked at four sets of prostate cancer screening recommendations, all from national organizations: the American College of Preventive Medicine, the American Cancer Society; the AUA and the U.S. Preventive Services Task Force (USPSTF).

After doing so, the Clinical Guidelines Committee of the American College of Physicians (ACP), a national society of internal medicine physicians, issued two guidance statements. ACP wants all clinicians to tell their male patients who are 50 or older and under age 70 that the positive effects of screening for this malignancy are limited and there are considerable potential negative effects.

That being said, if I were an African American man in that age range I'd be much more likely to ask to be screened. Both the incidence rate and the mortality rate from prostate cancer are higher in black men. And if I had a family history of the disease in a first-degree relative (father, brother or son), I might be first in line for a PSA and possibly a DRE. With one such having had it, my risk doubles and with two close relatives having the disease, my chances go up fourfold. That's especially true if they were diagnosed before they turned 65.

Overall a sixth of all men will eventually be diagnosed with cancer of the prostate. It will lead directly to death in a much lower percentage (2.9% was the figure the ACP quoted from a National Cancer Institute fact sheet). So although 2.3-2.5 million men in this country are living with this malignancy and last year nearly a quarter of a million got the diagnosis of prostate cancer in the U.S., a considerably smaller number were likely to die from the cancer itself.

Why does this make sense?

Well let's start with the second of the ACP's guidance statements: the organization says that men with an average risk of the disease shouldn't be screened until they are 50 and those of us 70 and older also should avoid having a PSA as a cancer screening tool. They go further and say men who are not expected to live more than 10 to 15 more years also should not be screened.

The fact sheet from the Prostate Cancer Foundation says it is the most common non-skin cancer in America with a new case very 2.2 minutes and a death every 17.5 minutes. But it's rare in men under 40 with 1 in 10,000 being diagnosed with the ailment versus 1 in 14 who are aged 60 to 69.

If we look at the totals: 97% of men diagnosed with prostate cancer are 50 or older and nearly two-thirds  are over 65.

The USPSTF came out with an update to their take on screening guidelines in 2012. They agree that the benefits of these tests, primarily the PSA, are less than the potential harm associated: false-positive tests, psychological effects, biopsies that are not necessary and over-diagnosis of cancers that often do not reach any clinical significance in the lifetime of the patient involved.

In other words, elderly men may well have prostate cancer, but they most commonly die from something else. And screening men at age 40, as the AUA suggest, doesn't appear to be based on any major studies.

If you are a man over 50, but less than 70, or black or first-degree relatives (father or brothers) have had the disease, have a sincere talk with your doc about the risks and benefits of screening.

But I don't fit into any of those groups, so I don't plan to get a PSA unless or until I see different data.

Thank you, ACP, for clarifying the subject, especially since you agree with me.



Prostate Cancer Controversies

Friday, September 7th, 2012

A prostate cancer awareness symbol

Prostate cancer is the most common cause of cancer death in older men. A few years ago most of us males over the age of forty (it seldom occurs before that) were periodically screened for the disease using the PSA test (a blood test for a prostate-specific antigen) and had digital rectal exams to check the size and consistency of our prostates whenever we had our yearly appointment for a physical and also had comprehensive lab work done.

Then things changed: the annual medical exam was discarded by most physicians in favor of a targeted examination, which in my case, with my history of high blood pressure, includes a nurse taking my BP and my doc listening to my heart and lungs. Not much else, unless I have a specific complaint. I'm 71 and haven't had a digital exam for five years. I had a PSA done when blood was drawn for other reasons and it was 0.7, well under the level that would have raised any concern about my prostate.

In October, 2011, the Harvard Health Blog provided two points of view on pending new recommendations for prostate-specific antigen (PSA) testing from the U.S. Preventive Services Task Force. A panel of experts after a thorough review of the literature on prostate cancer had concluded, that for men over 50, screening using the PSA test offered a low benefit to risk ratio. A huge controversy broke out with the American Urological Association arguing against the proposed new concept. Other physicians noted that an elevated PSA doesn't always mean cancer and, much more importantly, doesn't  distinguish which cancers of the gland are likely to be fast-growing and life threatening.

Oncologist, Dr. Marc Garnick, editor of Harvard's "Annual Report on Prostate Diseases," noted that the new testing recommendation was not a blanket statement fitting all men: those at higher risk (African-Americans and men with family history of cancer of the prostate) may still be suitable candidates for annual PSA testing. He later published an article in Scientific American mentioning that the use of regular PSA testing had led to over a million men having treatment for prostate cancer since 1985 and many thousands of men having complications of prostate surgery or radiation therapy (impotence, incontinence, rectal bleeding).

Dr. Garnick basically agreed with the task force's conclusions; felt the evidence supporting regular PSA testing was flimsy, but thought that the procedure gave important information after a cancer of the gland has been diagnosed.

Garnick was interviewed by a senior editor of the magazine and the resultant February 8, 2012, piece supplies audio comments from Dr. Garnick which detail some of the issues. One such concerns a man who has had his malignancy removed by a total (radical) prostatectomy. His PSA should plummet down to undetectable levels and, if it doesn't, either not all the cancer was excised or there has been spread beyond the local area (metastases).

I was reading my email a few days ago and noted one from my friend Rick with a link leading to an article from the Fred Hutchinson Cancer Research Center in Seattle titled "Prostate Cancer: 6 things men should know." There were six myths rebutted and I especially noted four conclusions: eating tomato-based foods and products doesn't prevent the malignancy; high testosterone levels don't correlate with risk of this tumor; omega-3s don't lower the risk (actually very high blood levels in one study were associated with higher risk); dietary supplements (selenium and vitamin E) don't prevent the disease.

At age 50 and above, this was on my schedule; at age 71 it's not

Another online publication from the Hutchinson Center gives background information on prostatic cancer. They note the frequency of the disease increases in men over 55, that obese men have a higher risk of developing an aggressive form of the disease, as do smokers. Those who drink red wine (four 4-ounce glasses a week) were noted to have a 60% lower incidence. Older men may receive unnecessary surgery; in this group the malignancy, often small and slow-growing, may not be life-shortening.

The need for screening in the general population of men is an ongoing medical controversy. We'll likely hear much more about PSA testing, but many would concede that a new type of evaluation needs to be developed.

I agree and for now I don't plan to have any more PSAs drawn.




Which study should I believe?

Wednesday, October 26th, 2011

Vitamin E has this chemical structure

I just read the recent (Oct 12, 2011) JAMA article on "Vitamin E and the Risk of Prostate Cancer." It was a long-term, prospective, randomized study of 33,533 men followed in 427 study sites in the US, Canada and Puerto Rico. The investigators were from major academic centers, Duke, the Cleveland Clinic, Brigham and Woman's Hospital (e.g., Harvard) and the National Cancer Institute among them.

This was an impressive study of the effects of Vitamin E and/or selenium versus placebo that began in 2001 with the subjects being "relatively healthy men." Seven years after it began, in September 2008, the independent data and safety monitoring committee decided that the supplements should be stopped as there had been no positive results (reduction in prostate cancer detection) and futility analysis (a statistical tool) said the results were quite likely to be negative (more cases of prostate cancer). I hadn't heard of that term and found a medical website that discussed a number of reasons for ending a study prior to the intended date. I'll paste in the URL if you want to read a one-pager on what is called "interim analysis."

In this study, though the researchers stopped giving supplements and published an article (JAMA.2009;301(1):39–51) on the results to date, which showed a higher (but not statistically significant) number of cases of  prostate cancer in the groups receiving Vitamin E, selenium or both, they also continued following the patient group.

Prostatic cancer under the microscope

The later data, though July 5, 2011, was quite impressive. There was a 17% higher incidence of prostate cancer in the group taking Vitamin E. In most scientific studies a p-value of 0.05  is felt to be significant. That translates to a probability of 5% or less that whatever happened did so by chance. If the data calculates to a p- value of 0.01, there's a 1% chance this was a random occurrence. Here, after ~eleven years the p-value for Vitamin E increasing the chance a man was diagnosed with prostate cancer was 0,008. (I'll paste in a website that explains more of this stuff if you're remotely interested).

Why all the math and statistics?

Well, for starters, a few years back a large study showed the exact opposite, but in a highly selected group: men in Finland who were smokers. Another study, done with physicians as the subjects, showed no effect on the incidence of prostate cancer. A post by a physician harshly criticized the SELECT trial as part of a lengthy defense of supplements, but made sweeping pronouncements without supplying data or references to specific articles.

I read the articles, the blog post and the new study in detail. I know that medical research projects often come to conclusions that, a few years later, are "proven" incorrect. But I think this study was carefully done, had a clear-cut purpose in mind and included a large enough group of subjects that I'm going to believe its conclusions.

Plus I'm certainly not a Finnish smoker.