Prostate cancer is firmly perched atop the leaderboard for male cancers, being more than twice as common as No. 2 lung cancer, and more than three times as common as No. 3 colon cancer.
That‘s why, if you are of a certain age and have a prostate, or know someone who does, the subject of “prostate cancer” has probably come up. But there’s good news. Although prostate cancer is king, it’s not the dark viceroy that is lung cancer, which causes twice as many deaths as prostate cancer.
This discrepancy in lethality is explained by the fact that prostate cancer is often a less aggressive, smoldering kind of cancer. It can dawdle along for years without causing any symptoms until the “host” dies of something else — most commonly, a heart attack or stroke (cardiovascular disease) or a different, more aggressive form of cancer.
Autopsy studies have found microscopic pockets of cancer in about a quarter of men in their 30s. By the time we reach our 60s, that number is more than 50%, and continues to increase with age. The question isn’t, “Will I develop prostate cancer?” because most men will, on a microscopic level at least, if they live long enough. The questions is, “Will I get the kind of prostate cancer that will shorten my life; and if so, can treatment extend my life, or will it just needlessly complicate it?”
Does all prostate cancer need to be treated?
Recently the New England Journal of Medicine (NEJM) published 15-year follow-up data for the ProtecT trial, which enrolled 2,600 men who had been diagnosed with prostate cancer that was mostly low grade and appeared to be confined to the prostate. These men were then randomized to one of three options:
- Surgical removal of the prostate.
- Radiation to the prostate.
- “Active monitoring,” which also has been termed “active surveillance.”
In the ProtecT trial, active monitoring meant following prostate specific antigen (PSA) levels. If a sharp, 50% rise in PSA occurred, options were to:
- Continue watching PSA levels.
- Get imaging studies like CT or MRI to see how much trouble might be brewing.
- Start treatment.
Over 15 years of follow-up, the study found:
- Very few men — around 3% — died from prostate cancer. Getting surgery or radiation treatment didn’t seem to offer any statistical benefit over active surveillance.
- 19% of the men (ages 50 to 69 at the start of the study) had died from something else.
- By the end of the trial, 60% of men in the active monitoring group had elected to get treatment with surgery or radiation.
- Advanced, widespread prostate cancer — typically into the bones — occurred in ~9% of the active monitoring group, and ~5% of the treated men.
What can we conclude from this study?
Prostate cancer is common but it is not a common killer. Most men will die from something else first.
It is psychologically challenging and anxiety-provoking to be diagnosed with cancer and then decide to just watch it. Sure, fine, the tests showed it was low-grade, and the doc said it probably won’t ever bother you. But at some point, 60% of the active surveillance group decided they were done actively surveilling and opted instead for actively treating with surgery or radiation anyway. They wanted it out, gone.
The staging system used in this study — which gathered data from 1999 to 2009 — was imperfect. A strong majority of men were thought to have low-risk cancer based on PSA levels, tissue biopsies (graded with what’s called a Gleason score), and ultrasound and CT imaging. In other words, staging showed the cancer cells did not have an aggressive, malevolent appearance, and the cancer looked to be confined to the prostate.
Unfortunately, for a small percentage of men, that wasn’t true. The prostate cancer recurred even though the entire prostate had been either surgically removed or “killed” with radiation. That’s because, on some microscopic level that could not be detected with the staging system used in this study, the cancer had already left the prostate at the time of treatment. We doused the fire but left some embers.
Our ability to accurately diagnose prostate cancer continues to improve
The NEJMstudy was accompanied by an editorial written by Oliver Sartor, M.D., a prostate cancer expert who was not involved with the study. Dr. Sartor politely noted that although the findings were useful, “… the management of localized prostate cancer has undergone a wholesale change since 1999 when the ProtecT trial was started.” This is a common problem for all long-term studies: By the time a study ends and the data is collected, analyzed and published, the science has advanced.
As Dr. Sartor catalogues, we’re getting more sophisticated when it comes to figuring out how aggressive and widespread any particular case of prostate cancer might be.
Whereas the Gleason score is determined by a pathologist viewing cancer cells under a microscope, newer technologies are going even deeper, looking at the genetics of malignant cells. Does the cancer have the kind of mutations that put it into the high-risk, aggressive category?
Rather than ultrasound, MRI imaging is increasingly being used to provide a much more detailed view of the prostate gland — and surrounding lymph nodes and organs — allowing for biopsy of the most suspicious areas. Better targeting means better biopsies, since we know the biopsy needle is inserted into the most aggressive-looking portions of the cancer.
The sharp eye of MRI imaging is also spearheading research into what are termed “focal therapies.” Rather than radiating or surgically removing the entire prostate, the cancerous portion of the prostate can be destroyed by freezing it — a therapy called cryoablation — heating it with either a laser or high-frequency ultrasound, or by using electric pulses to riddle cancer cells with tiny but lethal holes, a technique called irreversible electroporation.
Like the MRI, a relatively new imaging test called the prostate-specific membrane antigen (PSMA) positron emission tomographic (PET) scan will help “see” prostate cancer on a more microscopic scale. For years, men with biopsies showing high-grade, high-risk prostate cancer would have a CT scan, or a test called a bone scan, to see if the cancer had spread. Unfortunately, neither of these tests can see microscopic amounts of cancer, so high-risk patients would undergo prostate surgery or radiation with the goal of cure, only to find out months or years later that the treatment came too late. The cancer had spread.
In a PSMA PET-CT, a molecule that binds to PSMA (a protein found in large amounts on prostate cancer cells) is injected along with a radioactive tracer. This causes microscopic areas of cancer to “light up” on the PET scan. Early trials show PSMA PET-CT to be 27% more accurate than conventional CT and bone scans
The risks of the most common forms of prostate cancer treatment (surgery and radiation)
Many medical decisions are a value proposition: What will it cost in terms of risks and side effects and what will I get in return, such as a better or longer life. A companion article in the NEJM looked at the “cost” side of the equation for men who were 7 to 12 years into the ProtecT trial.
The cost part of prostate cancer treatment includes, most prominently, the risk of the “droops and dribbles” — erectile dysfunction (ED) and urine leakage (“incontinence”).
With urinary leakage — enough to require the use of pads — those who had surgical removal of the prostate had the highest rates seven years into the study at 18%, compared to 3% of those treated with radiation and 9% of those with active surveillance. At 12 years, 24% of study participants who had surgery had urinary incontinence, compared to 8% of the radiation group and 11% of those in the active monitoring group.
Seven years into the study, 18% of the surgery group reported erections sufficient for intercourse, compared to about 30% for the radiation and active monitoring group. At 12 years out, all three groups had declined to low levels of potency, presumably due to a “sand through the hourglass” phenomenon.
Surgery did have one upside: Removing the prostate improved one of the most pesky symptoms of an enlarged prostate — having to get up at night to pee. Roughly 35% of surgery patients noted having to urinate at least twice at night, compared to about 50% for the other two groups.
Radiation had one troublesome downside: stool leakage. Because the prostate gland sits right next to the rectum, there is a risk of collateral damage. However, the more refined radiation has become, the less of that there is. Twelve years out, 12% of men treated with radiation had problems with stool leakage, compared to 6% for the other two groups.
Despite the variability in these side effects of treatment, all three groups had similar quality-of-life scores.
Bottom line: In older men, prostate cancer is most often a slow-growing, smoldering process — where treatment might complicate one’s life rather than prolong or improve it. Hopefully, increasingly sophisticated testing will help all of us — patients and physicians alike — decide who will benefit from aggressive prostate cancer screening and treatment, and who should just let things be. After all, the treatment shouldn’t be worse than the disease.
