What do Rudolph Guliani, Robert Diniro, Dennis Hopper, James Brown, Arnold Palmer, Joe Torre, Dan Fogelberg, Colin Powell, John Kerry, Johnny Ramone, Francois Mitterand, Robert Frost, and Frank Zappa have in common?
They have lived with, or died from, prostate cancer.
Every 19 minutes, an American man dies from prostate cancer, and it is the second leading cause of cancer death among men, and it is the most common cancer in men, yet it remains the bastard stepchild of cancer awareness. Add to “in the shadows” publicity, a call from many organizations for men not to even bother being tested for indicators of prostate cancer.
Certainly, prostate cancer organizations are not nearly as mobilized as, say, breast cancer campaigns, but that may all change soon. Prostate cancer is an elusive chameleonic cancer that can, on one hand, be so slow-growing as to be considered nearly benign; or it can spread rapidly, often to the bones, triggering a deadly fight with a much more persistent and pervasive disease.
African American males inexplicably have a mortality rate more than 2.5 times that of Caucasians; new cases among the African American population are diagnosed at a rate of 220/100,000 in contrast to 138.6/100,000 for Caucasian males. Roughly, one in six men will be diagnosed with prostate cancer in their lifetime, and one in six of those will die from it.
Diagnosis of prostate cancer can be tricky due to the technologies available. Generally, a spike in a man’s Prostate Specific Antigen (PSA) is a red flag, as are lumps or other irregularities detected by a digital rectal exam. The latter, often a source of jokes and anxiety, is extremely valuable for prostate cancer detection, while the former, the PSA test, is at the heart of a storm of controversy. Only in the past two years have DNA genetic testing methods provided some insight as to predicting the biological nature of prostate cancer. We’ll return to that critical topic in a moment.
The good news is best summarized in a commonly-heard adage regarding prostate cancer: most men will die with prostate cancer rather than from prostate cancer. Indeed, some prostate cancers are so slow growing that most men run out of years before any danger is presented by the disease. But not all prostate cancers are created equal, and for prostate cancers deemed aggressive, treatment is strongly urged, and that’s where life gets complicated.
It is known that prostate cancer growth is often dependent upon male sex hormones called androgens, one of which is testosterone. This is why men diagnosed with prostate cancer are cautioned not to succumb to the popular wave of “Low T” testing prevalent on television and radio ads these days. Plying upon men with decreasing sex drive, and increasing midsections, and lowered energy, testosterone therapy (often resulting from the Low T testing process) will accelerate the progression of prostate cancer.
The good news is that early detection results in an extremely high cure rate for prostate cancer. Stage I cancers boast survival rates in the mid-to-high 90-percent range. The bad news is that many of the popular available treatments have at least some drawbacks.
To understand why, one has to understand that the prostate is to the human body what Caroline Island is to geography — remote, difficult to access, and surrounded by challenges. Sitting just below the bladder, the donut-shaped prostate encircles the urethra — that’s the first problem, though that specific limitation is more an inconvenience for surgeons. The real problem with dealing with the prostate is that nerves for sexual function and bowel continence are close by, and are largely invisible to current imaging and visualization techniques. Damage to those nerves can precipitate a host of issues — all bad.
The Diagnosis Jungle
Among many professionals and health agencies, there is a very heated debate with diametrically-opposed viewpoints, largely around the aforementioned PSA testing.
PSA testing is still an indicator of problems that may include prostate cancer. Many men, particularly over 50, who are at greater risk for prostate cancer, include it in their yearly physicals. It is a simple blood test that indicates the levels of PSA in the blood. So, why in the hell would you NOT want to know your PSA level, especially realizing some prostate cancers are fast growing and lethal? It seems to make both common and scientific sense.
The answers are complex and driven by statistics.
The chief complaint is attributed to the imperfect nature of PSA tests. There are many things that can drive PSA values high; infection, benign enlargement, and injury among them. Because PSA tests are only an indicator, many urologists will recommend a biopsy — the only current method for determining the presence of, and the relative likelihood that the cancer is fast growing.
Critics of PSA testing point to the high number of false positives, many of which result in “unnecessary” biopsies. They also discuss the potential for “over treatment” and the side effects resulting from those treatments. Many proactive men with positive biopsies will opt for treatment: “Get the damned stuff out of my system — NOW!”
But if the cancer is of the slow-growing type, the chances of dying from it are very small. However, fast-growing cancers that metastasize, spread prostate cancer cells to the bones, and that is a very problematic eventuality. Fast-growing and metastasizing prostate cancer is a killer.
Agencies, such as the U.S. Preventative Task Force, a non-governmental panel of independent experts in prevention and evidence-based medicine, recommend that doctors cease PSA testing to screen men with no symptoms of prostate cancer. That same task force stated that the standard treatments sometimes have outcomes worse than the disease. Indeed, the panel considered only conventional treatments such as robotic surgery, radiation, cryosurgery — and not some alternative treatments not yet available in the United States.
On the other hand, many practicing urologists, and I have several as friends and healthcare providers, all say the same thing: “I get my PSA measured and so should you.”
In fact, estimates indicate that, without PSA testing, perhaps 17,000 men would proceed to the deadly metastatic cancer stage that could have been potentially detected had they been tested. My personal urologist reacted to the recommendation against PSA testing by saying, “Yes, if people follow that advice, the first thing we’ll see is a huge increase in bone cancers.”
Critics argue that there is no clinical data to support that conclusion.
Even the American Urological Association has released new recommendations in terms of not recommending PSA testing for men under the age of 55 with no symptoms. Indeed the American Cancer Society recommends that men hold off starting PSA testing until age 50.
But, while we have focused on false positives, there are also false negatives.
A friend of mine went in for his annual physical, and his PSA was totally within normal ranges, but a digital rectal exam determined lumps in his prostate. He underwent a biopsy, a fast-growing malignancy was found, and the recommendation was for robotic surgery to remove the prostate, which had swollen to massive proportions — yet, as mentioned, his PSA was normal. It should, therefore, be noted that normal PSA readings don’t rule out the presence of cancer — clearly, we are in need of better diagnostic tools.
I spoke to one of the world’s leading urologists for this article, and he cautioned that the most important prostate cancer decisions should not be those derived from scientific papers documenting studies with large numbers of patients, rather, the patient should examine their own feelings, their own health, their own ability to accommodate risk, and then do their research — speak to patients (they are all around you), talk to doctors, emphasizing more than one — and make an informed decision.
So, if the experts can’t agree, what are we, as laypeople, supposed to do?
A close friend of mine, at the time, 55 years old, told me he never had PSA done because his general practitioner recommended against it. Now, four years later, he called me to say he had one in his routine physical a few months ago, and his PSA was 22. Although the rules aren’t hard and fast, PSA levels of 4.0 ng/ml and under are considered normal. A digital rectal exam was performed and no lumps were detected. Thinking an infection was a possibility; his GP put him on antibiotics for a few weeks (Cipro, the “Anthrax Medicine,” was prescribed). After the regimen of antibiotics was completed, his PSA had not dropped and, in fact, it had risen to 24.5. I asked my local urologist about that number, and he said, “In all my years, I’ve never seen a number that high without lumps being detected by a digital rectal exam.”
My friend proceeded to the biopsy, and cancer was detected in half of the 12 core samples taken.
What were those PSA levels a year ago? We won’t know, because he wasn’t tested.
But many urologists are more concerned about a series of PSA measurements over time rather than a single number. Some urologists liken “serial PSA” measurements to x-rays or mammograms from the perspective that it’s about change in values over time, rather than that one measurement.
Torn between testing or not? A few quotes:
“I think they (the critics of PSA testing) overestimate the importance of the side effects over that of being cured. People who are incurable at the time of their diagnosis feel that way even more strongly. From my standpoint, you should concentrate on getting the cancer out of your body and then deal with the side effects. If you don’t catch the cancer early when you can still cure it, the rest of it doesn’t matter.” — Richard Howe, retired president of Pennzoil
“Obviously, there is a divergence of opinion about the need for early detection of prostate cancer. To me, I don’t understand why there is any controversy.
“When I started my fellowship in 1978, all we saw was prostate cancer in people with metastatic disease (meaning the cancer has spread). That has changed dramatically since PSA came on the market.
“Not everyone with prostate cancer needs to be diagnosed, not everyone with a diagnosis needs to be treated. Not everyone dies with disease. But all that has to be placed in the perspective of the simple fact that prostate cancer is the second-leading cause of male cancer deaths. You can’t ignore that fact.” — Richard J. Babaian, Professor of Urology at M.D. Anderson Cancer Center
Indeed, William Catalona, Professor of Urology at Northwestern University in Chicago, developed the PSA test. Catalona and others would like to begin testing in men at age 40 and lower the threshold for risk from a PSA level of 4 to 2.5. They believe they would be able to diagnose aggressive cancers at even earlier stages and provide treatment that has a greater chance of a cure.
Catalona’s data show 90 percent of men 50 and older have PSA levels below 4. About 8 percent have a PSA level between 2.5 and 4. Of these men, PSA levels will rise above 4 in 50 percent within four years.
Because the prostate is so close to the intestine, during a digital rectal exam, physicians, using a finger, feel right through the wall of the intestine and can determine if the prostate has an abnormal texture or lumps. Most urologists have performed countless thousands of these exams and are quite skilled at detecting anomalies.
The biopsy process is uncomfortable in some cases, but usually not overly painful, particularly when a mild oral painkiller is used along with some local anesthesia or what is referred to as a prostate block. A special instrument is inserted up the rectum and guided with ultrasonic images. A biopsy needle is propelled through the wall of the intestine into the prostate, a sample is collected, removed, labeled and then the next needle is inserted. The process is repeated, usually, for 12 samples.
These samples are sent to a pathology lab, and examined by experts who then classify the samples as positive or negative; the amount of the core deemed to be cancerous, and then the pathologist assigns a number called the Gleason Index to the sample. The Gleason Index indicates whether the cancer is slow-or fast-growing. The Gleason Index, the cancer stage, the number of positive cores (samples), as well as the percentage of cancer in each sample, and a few other factors, are all critical tools for recommending treatment.
Current treatments include:
- active surveillance
- radiation therapy
- hormone therapy
Before we get into a discussion of the various ups and downs of these treatments, know that you can speak with 10 urologists and get 10 opinions. Probably the toughest part of prostate cancer is deciding upon a treatment.
And then we have the Stark Law.
Briefly, it is the practice of a physician referring a patient to a medical facility in which the physician has a financial interest, be it ownership, investment, or a structured compensation arrangement. Critics argue that this practice is an inherent conflict of interest, because the physician benefits from the physician’s own referral.
Does it happen? Most of the physicians I’ve asked about say “yes, of course,” but the obfuscation of such relationships has become more — sophisticated.
As an example, let’s say a company manufacturing a radiological instrument used for a specific type of treatment buys a number of urology practices to farm those practices for referrals. Is that a conflict? How could you tell if a patient was being urged to consider that company’s technology above all others?
If you or anyone you know is facing prostate cancer, thorough research is a must — ask questions, and get several opinions. Remember, to a hammer, everything looks like a nail, and if you speak to a urologist specializing in robotic surgery, for example, he or she will actively promote robotic surgery. A radiological oncologist will favor some form of radiation therapy.
For cancers at a lower Gleason number (usually 6), an early stage, and a lower PSA, so-called watchful waiting is recommended for those with steely nerves. Those three elements statistically indicate a very slow-growing cancer that may never accelerate. Unless a subsequent PSA spike, detectable lumps, and/or a biopsy indicate further action is required, routine checkups are the normal pathway.
In the United States, surgical removal of the prostate is perhaps the most common treatment. Most often, the physician is aided by a da Vinci robotic surgical system. Using high-definition monitors, and robotically-assisted tools, the physician makes small, precise cuts and removes the prostate. While often very effective in terms of long-term success, the tricky part of this process is that the aforementioned threadlike nerves are easily damaged, and men can suffer minor or major incontinence and/or impotence.
This approach takes two fundamentally different forms: External Beam Therapy (EBT) and Brachytherapy.
Probably the most complex, confounding, and often contradictory debates among medical professionals surrounds the two basic forms of EBT. There is no way I can delve into these treatments without oversimplifying, and likely doing a disservice to them. As a disclaimer, if you are investigating these technologies, please, please, please obtain several opinions.
In general, there are two different approaches to EBT: photons and protons. One is electromagnetic radiation while the other consists of subatomic particles. The very general debate surrounding these techniques is that the type of photons used in photon therapy, x-rays, release their energy before arriving at the prostate, while proponents of proton beams state that protons release their energy inside the prostate. Why is “where” the energy released important? It goes back to all of the tissues that the beam must traverse before hitting the target areas of the prostate. There is always a concern when healthy tissue is exposed to radiation, and a fear that other issues may eventuate down the road, years later. The longer-term concern is that the radiation exposure would lead to bladder or rectal cancers.
Proton Beam Therapy has come under recent fire from insurers who see big price tags for the procedure, but little evidence that the technology performs better than other forms of EBT. http://www.wsj.com/articles/big-bets-on-proton-therapy-face-uncertain-future-1432667393
Of course, if you read the background pages of each technology, there are exhaustive discussions about radiation levels and precision targeting. Regardless of approach, the idea is to wipe out the cancer cells with a beam of radiation.
In a procedure somewhat similar in approach to a prostate biopsy, tiny radioactive “seeds” are implanted by the physicians near the areas where the biopsy indicated cancer. These seeds have a short half-life, so after a while, they cease to emit radiation, but when they are first implanted by the physician, patients are warned not to hold children on their laps for a few days. Again, as this treatment involves ionizing radiation, meaning radiation that can fundamentally trigger the release of electrons from atoms, there is always a concern about the radiation harming nearby tissue, such as the bladder or intestine.
More popular a few years ago than now, cryotherapy involved the insertion of tiny probes near the cancer cells that could be cooled to such a temperature that they could kill off the cells by freezing them. The procedure is conducted in much the same manner as a biopsy. Again, the close proximity of nerves that can also be frozen is a concern. There are some opinions stating that whole-gland cryotherapy has an extremely high (nearly 100 percent) chance of causing impotence.
Also known as androgen deprivation therapy (ADT), androgens are necessary for not only normal prostate growth, but also contribute to the growth of cancer cells. In general, this approach is used for prostate cancer that metastasized or as a form of treatment for a recurrence as indicated by a rising PSA after primary treatment. It is not normally considered a long-term strategy, and carries with it the stigma of another name associated with it: chemical castration.
A number of vaccines have been approved to combat advanced prostate cancer, but most have limited effect and may only extend survival by months in these patients. More promising approaches include virus-based, checkpoint inhibitors, immune modulators, and adoptive cell therapies. Many of these are in various stages of clinical trials and, thus, have limited data associated with them.
Generally used after hormone therapy fails in advanced prostate cancer, some chemotherapy approaches have indicated up to a nearly two-year extension of patient lives. Again, many clinical trials are in play for evolving chemotherapy drugs.
Called High Intensity Focused Ultrasound, (HIFU), this technique has been widely used outside of the United States, but has yet to gain FDA approval in the U.S. In this approach, the physician, using the results of a biopsy as a guide, places a probe in the rectum of an anesthetized patient, and a computer maps the dimensions of the prostate in a three-dimensional model. This is the most time-consuming part of the procedure. When the mapping has been completed, the probe emits converging beams of ultrasonic energy that ablate tiny areas of the prostate as dictated by the computer. Specific zones can be targeted, or the entire gland. Studies outside of the United States indicate success rates similar to surgery, but there are vocal critics of the procedure, as is often the case with new and disruptive technologies. It is described as a non-invasive, painless procedure that delivers ultrasound energy to the cancerous tissue where it is converted to heat.
One of the main strengths of the procedure is the claim that there are fewer side effects — meaning less incontinence or impotence, and there is no fear of the side effects associated with ionizing radiation therapies, as ultrasonic energy is non-ionizing. The rationale behind such claims is that the ultrasonic energy does not propagate beyond the targeted areas. Many U.S.-based physicians are trained in HIFU, and conduct the procedure outside the country, such as in Canada, Mexico, the Bahamas, Caymans and a few other locations. My personal urologist when I lived in Atlanta (and squash-playing buddy) was one of those physicians. Harvard-trained, he is a huge HIFU proponent, and routinely treats patients in Canada, his home country. Another friend of mine had to have a complex bladder construction procedure as a result of bladder cancer. His physician, a pioneer of the reconstruction procedure, was also an enthusiastic supporter of the procedure. But clinical trials are still underway in the U.S., and while there is hope the procedure will be approved here soon, most insurance companies will not cover the procedure, so financial ability comes into play.
What to Do?
Which therapy is “best”? The simplistic answer is whatever the patient decides.
But the Prostate Jungle is more dangerous and difficult to navigate than the deepest part of the Congo. Perhaps it’s a function of my age, or perhaps increasing awareness is leading to more testing and diagnosis, but I learn of someone I know with prostate cancer every other month.
I’m not going to try to persuade those dealing with a prostate cancer diagnosis to seek out a specific treatment. I’m not even going to try to convince you to get your PSA checked. There are too many researchers and doctors out there who have devoted their lives to dealing with this disease who can raise compelling arguments in any direction.
Do not use this column to make any sort of decision if you are facing one. Talk. Ask.
All I’ve tried to do is to raise your awareness level. I think if any of my readers feels that they now have a stronger understanding of the disease, the diagnosis and the treatments, then I’ve done my job.
Randy Hice is a leading authority in the field of laboratory informatics and currently works for a global healthcare company. He may be reached at editor@ScientificComputing.com.