Prostate cancer in younger and older men

Content provided by the Faculty of the Harvard Medical School

Prostate cancer in younger and older men

Most malignancies become progressively more common as people age. For prostate cancer, the trend is particularly striking. The estimates of the U.S. Preventive Services Task Force demonstrate the effect of age on a man's risk:

Until PSA testing became widespread in the early 1990s, most prostate cancers in younger men were detected because of symptoms or abnormal findings on a doctor's digital rectal exam. In contrast, many of the prostate cancers in older men were diagnosed as incidental findings in the course of surgery for benign prostatic hyperplasia (BPH) or during autopsies, after a man had died of other causes. As a result, younger men often had more advanced disease at the time of their diagnosis than older men, so younger men seemed to respond less well to therapy. That led to the widespread belief that prostate cancer tends to be very aggressive in young men while it's often quite indolent in older gents.

PSA testing has produced a dramatic change in the detection of prostate cancer. In the United States, the number of diagnosed cases soared by 30% a year between 1989 and 1992 before settling down to the current level of about 220,000 new cases a year. It is also being diagnosed at an earlier stage and at a younger age. Before the PSA came into wide use, fewer than 1% of cases were detected in men younger than 50, but in some studies, up to 4% of cases occur in that age group.

These changes are dramatic, but doctors don't yet know if they will add up to improvements in the length, or quality, of a man's life. Clinical trials are needed to answer this critical question, and three major studies are already in progress. But even as scientists await the results, they have begun to re-evaluate the idea that prostate cancer is more likely to be lethal for younger than older men. Four American studies provide interesting insights.

Young men

Prostate cancer is being diagnosed more often in young men. The American Urological Association (AUA) and the American Cancer Society (ACS) recommend that doctors discuss the pros and cons of the PSA test and offer it to men annually starting at the age of 50. But they also suggest that doctors start the discussions at age 40 (AUA) or 45 (ACS) for men at higher than average risk, including African Americans and those with strong family histories of the disease. Another trend that is leading to increased diagnosis in young men is the use of age-adjusted PSA ranges. Most doctors use 0–4.0 ng/mL (nanograms per milliliter) as the "normal" range of PSA values for men of all ages, but some centers have lowered the bar to 0–2.5 ng/mL for men younger than 50. Finally, with increased awareness of the disease, many men are requesting, and getting, the PSA test long before they come "of age."

Most men who are diagnosed at a young age choose surgical treatment. But even though nearly all patients come through the surgery, many become impotent and some develop incontinence or other complications. It wouldn't make much sense to risk all that if the disease were too aggressive to respond to surgery — two studies say that is not the case.

The first investigation was performed in six military medical centers in all parts of the United States. It compared 79 men diagnosed with prostate cancer at the age of 50 or younger with 398 men diagnosed between 51 and 69. All the patients underwent radical prostatectomies between 1988 and 1997. The two groups did not differ in their racial composition or in the clinical stage of their disease. However, the older men did have higher PSA levels at the time of their diagnosis, and they were more likely to have disease that had spread beyond the prostate at the time of surgery (52% versus 35%).

The researchers tracked the patients for 1–10 years following surgery. In all, 7.6% of the younger men had a recurrence of their cancers; 26.9% of the older men developed recurrent disease. Because the younger men were diagnosed later in the study period, they had a shorter average follow-up (2.8 versus 4.5 years). Still, there were fewer recurrences per year in the men under 50 than in the 51–69 bracket. That's no surprise, since the younger men tended to have earlier disease at the time of surgery. But the scientists repeated the analysis with adjustments for race, PSA, clinical disease stage, and pathological findings, only to find that the younger men still had better disease-free survival rates.

The study did not analyze surgical complications or quality of life. And since the follow-up was relatively brief, it did not evaluate longevity. It also did not compare surgery with radiotherapy or other treatments, nor did it investigate the value of early diagnosis by comparing men who had PSA screening with those who did not. But despite these limitations, the study argues against the traditional view that prostate cancer is more aggressive in younger men.

The second, larger study, from Johns Hopkins Hospital, compared 341 men who were diagnosed with prostate cancer before the age of 50 with 2,556 older men. As in the earlier research, the younger men tended to have earlier disease at the time of diagnosis and surgery. And, as in the first study, the younger men tended to have better disease-free survival rates than the older men. Unlike the earlier research, the Johns Hopkins study did not adjust the survival rates for the severity of disease at the time of diagnosis (a weakness), but it did extend the follow-up period (a strength).

The third study evaluated 1,753 men treated with radical prostatectomies at five medical centers between 1988 and 2002. The scientists compared men younger than 50 at the time of surgery with those aged 51–60, 61–70, and older than 70. Because the diagnosis in younger men has become more common in recent years, the average follow-up period was shorter (19 months) in the below-50 group than in the 51–60 (30 months), 61–70 (33 months), and over 70 group (51 months). The short follow-up in younger men and the lack of data on mortality are limitations of the study. Still, when the scientists evaluated PSA evidence of recurrent cancer, they found that the younger men had more favorable outcomes than the older men.

The fourth study, published in 2005, evaluated 790 men who had radical prostatectomies performed by a single surgeon between 2000 and the end of 2003. The extremely short follow-up makes it impossible to evaluate the things men care about most — the risks of recurrent cancer and death from cancer. But the surgical and pathological findings in the 66 men who were younger than 50 were entirely similar to the findings in the older patients.

Older men

A man's risk of developing prostate cancer rises steadily with each passing year, but his risk of dying from the disease does not. Does that mean the disease is less aggressive in older men or that older men are more fragile, so they die of something else before prostate cancer becomes lethal?

Researchers studied 120 men between 70 and 88 who were diagnosed at a Veterans Affairs hospital from 1994 to 1997. For the purpose of comparison, the men were divided into three age groups: 70–74 (75 cases), 75–79 (28 cases), and 80 and over (17 cases). The men over 80 had more advanced disease at the time of diagnosis; they had higher PSA levels, and their tumors had higher Gleason scores, which indicate a more malignant appearance. As compared with the youngest men in the study, the oldest were also less likely to choose surgical treatment and more likely to elect watchful waiting (observation without active treatment).

The men were tracked for 34–69 months. Although the risk of death was highest in the men over 80 (29%), none of them died from prostate cancer.

Based on this study, prostate cancer does not appear to be less aggressive in older men, but because older men are likely to have other, more lethal, problems, they more often die with prostate cancer than from it.

As time goes by

Like most malignancies, prostate cancer becomes more common with advancing age. Unlike most malignancies, however, it has a highly variable course. In most cases it is a slow-growing, rather indolent disease, but sometimes it's aggressive and lethal. In all, about 30% of American men will develop prostate cancer, but just 16% will have clinical symptoms of the disease and only 3% will die from it.

Doctors don't know if PSA testing and early diagnosis will improve the lot of men who develop clinical symptoms or reduce the prostate cancer death rate. Some worry that treatment may even do more harm than good for men with indolent disease. More research is needed to resolve these questions. But the studies suggest that the disease itself is not necessarily more aggressive in younger men. In fact, in the PSA era, older men are more likely to have advanced disease at the time of diagnosis — but they are also more likely to die from causes other than prostate cancer.

PSA testing for healthy men is controversial at any age, but it's most likely to help men younger than 70–75 and men who don't have other diseases that limit their life expectancy to 10 years or less. That's because prostate cancer usually grows slowly: It typically takes 10–11 years before it is large enough to be diagnosed. The average life expectancy of a 75-year-old American man is 9.8 years; even if PSA testing detected disease at that age, it's unlikely that the disease would grow fast enough to be fatal. Even so, more than 20% of the Medicare population is still getting PSA tests at age 85.

Age need not deter younger men from having a PSA test, but it should deter men above 75. When it comes to detecting occult prostate cancer in older men, at least, ignorance is bliss.

Last updated:	September 05, 2008