Choosing the Best Prostate Cancer Treatment for You

Surgery, Radiation, Active Surveillance, or Seed Implant?

Since there are three different risk categories of newly-diagnosed prostate cancer—low, intermediate and high—optimal treatment varies. In general, our approach is to recommend active surveillance to low-risk patients, seed implants to men with intermediate-risk disease, and a seed implant plus additional therapy to men in the high risk category. These decisions came about based on research that compared outcomes between the different treatments.

Surgery or Beam Radiation?

However, many experts disagree. Traditionally, only two types of therapeutic options, surgery or beam radiation, are presented by surgeons and radiation therapists, the doctors who generally manage men with prostate cancer. Active surveillance or radioactive seeds, also known as brachytherapy, are often left out of the discussion.

For years, the focus has been on the debate between surgery and radiation, the question being, “Is one option better?” And by “better”, we mean: which treatment has the highest cure rates and the lowest impact on urinary and sexual function?

It has long been suspected that surgery and radiation have similar outcomes, but quality scientific comparisons to determine if one is slightly better than the other have been lacking. Therefore, patients and doctors alike have relied on emotional and personal reasoning over informed, rational decision making.

However, men seeking answers are now blessed with a momentous new development—the publication of a head-to-head, randomized clinical trial comparing surgery, radiation, and active surveillance.

Randomized trials are special because they answer a specific question prospectively, enforcing the elimination of biases, a pervasive problem with retrospective trials (more than ninety-nine percent of trials comparing surgery and radiation are retrospective).

The reason there are so few prospective trials is that researchers have to find patients who are willing to have their treatment randomly selected.  In the trial discussed below, the men had to figuratively “draw straws” to determine who would undergo surgery, radiation or surveillance in a process called “randomization.” 

Numerous retrospective studies already exist, attempting to compare the outcomes of radiation and surgery. They are polluted, however, by many confounding factors, one example being the unequal age of the patients. Typically, younger men are allocated to surgery and older men are treated with radiation.

Comparisons like these are unfair because it is well-known that younger men have better results no matter what type of treatment is administered. Until now, since the only “scientific data” has been retrospective data derived from unequal groups, doctors have been free to pick whatever retrospective study supports their personal bias to defend the position that one treatment is superior the other.

What About Active Surveillance?

So why hasn’t there been any prospective data comparing surgery, radiation, and active surveillance? First, such trials are very expensive. Hundreds of men need to be monitored for over ten years. Second, it is difficult to find men who are willing to draw straws for treatment selection. Third, since trials take so long to mature, designing such a trial requires visionary brilliance to ensure that the question being answered by the trial will still be relevant 15 years into the future.

As difficult as randomized, prospective trials are to fund and perform, they are desperately needed. The absence of randomized trials almost always leads to controversy and indecision. Without definitive information, treatment selection ends up being driven mostly by financial considerations—the treatment that pays the best becomes the most popular. So the recent publication of several randomized studies directly comparing the treatment outcomes for surgery, radiation, and active surveillance is indeed historic. These are landmark events enabling us to finally know the true bottom line.

In September 2016, the New England Journal of Medicine published an article entitled “10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer”. In this trial, 1650 men were randomly assigned to active surveillance, surgery, or radiation, and followed for ten years. The type of men who participated in the trial were typical of the average man who is diagnosed with early stage disease via PSA screening. Their median age was 62. The median PSA was 4.8.

Three-fourths of the men had nothing palpable on their digital prostate examination and one-fourth had a palpable abnormality. Slightly more than three-fourths of the men were Gleason score six. One fifth of the men were Gleason score 7 and one out of forty men had a high Gleason score, of 8 to 10.

After agreeing to participate in the study, men were allocated to either immediate surgery, immediate radiation or active surveillance. Those who were assigned to surveillance had their disease monitored regularly so that treatment could be initiated as necessary.

Over the subsequent 10-year period of observation, approximately half of the men on surveillance underwent delayed treatment with surgery or radiation. Interestingly, most of the men in the surveillance who opted for treatment did so for emotional rather than rational reasons. In other words, they decided to have treatment even though in most cases there was no evidence that their disease was progressing. 

All three treatment groups were monitored for prostate cancer-related mortality. After ten years, there were 17 deaths related to prostate cancer spread evenly across the three groups—a 1 percent rate in each group—whereas 169 deaths occurred from other causes besides prostate cancer. Nine of the 17 deaths occurred in patients who had a baseline Gleason score of 7 or higher. Mortality was reported in 8 men with Gleason 6 but since this trial was designed many years ago, diagnosis relied upon random biopsy rather than imaging with multi-parametric MRI. Multiple studies have clearly shown that random biopsy misses higher-grade disease much more frequently than multi-parametric MRI.

The most important take away from this trial was that among all three groups, there was no difference in mortality rates over 10 years.

The Take Away of the Study

So according to this new and very reliable data, ten-year mortality rates remain statistically the same whether a patient chooses surgery, radiation or active surveillance. What about quality of life? A companion article to the one outlined above was also published in the New England Journal on the same date, reporting quality-of-life outcomes for each of the three treatments related to sexual and urinary function. Regarding sexual function, two-thirds of the men in the study were potent before receiving therapy. After one year, the percentages of men who retained potency, i.e., had erections “firm enough for intercourse” were as follows:

One year after embarking on the study the men were also queried about the presence or absence of urinary leakage requiring the use of pads. One percent of the men reported the use of pads before the start of the study. Problems due to excess night time urination were the same in all three groups and remained so after treatment. After one year, the percentage of those who used pads were:

  • Active surveillance = 4 percent
  • External beam radiation = 4 percent
  • Radical prostatectomy = 26 percent

Combining the results of the above two trials, we can now answer the question of which treatment has the highest cure rates with the least amount of side effects? Surgery, radiation, and active surveillance all have the same survival outcome, but active surveillance comes out with the least amount of side effects

One drawback to note regarding the active surveillance arm in the above trial was that cancer progression, i.e. incidence of metastasis was less prevalent in the men who had surgery or radiation compared to the men who were on surveillance—13 versus 16 versus 33 men respectively. Therefore, if we ignore quality of life altogether and define “cure rates” as “freedom from cancer progression,” rather than “survival”, the surveillance group is slightly worse off than the surgery or radiation groups, without any difference between surgery and radiation.

However, as noted above, one problem with interpreting trials that were designed 15 to 20 years ago is that they rely on potentially outdated technology. Cure rates for surgery and radiation have changed very little, if any, over the last 15 years.  

However, the monitoring technology for men on active surveillance has been greatly improved by the advent of accurate imaging with multi-parametric MRI. Modern imaging greatly reduces the risk of missing unsuspected high-grade disease, a common problem associated with monitoring that relies on surveillance with random biopsies. These days, multi-parametric MRI technology can ensure accurate categorization to reduce the risk of eventual cancer progression for men desiring to pursue active surveillance.

Radioactive Seed Implants

Another substantial technological breakthrough has been the realization that radioactive seed implantation results in higher cure rates than standard beam radiation. In another recently published landmark study comparing the outcomes of radiation alone versus radiation plus a seed implant, the cure rates with seed implantation was shown to be substantially higher. All of the men in this trial had unfavorable types of intermediate-risk or high-risk prostate cancer.

Five years after treatment, the cure rate for radiation alone was 84 percent whereas the cure rate for radiation and seeds was 96 percent. After nine years the advantage for seeds was even more stark. Without seeds the cure rate was only 70 percent while 95 percent of the men receiving the combination of radiation plus seeds remained cured.

Clearly seed implants substantially boost to cure rates. There is one addition new trial that examines how seed implants fare all by themselves, without any beam radiation whatsoever. This trial studied 558 men randomized between radiation plus seeds versus seeds alone. The average Gleason score was 7 and PSA was generally less than 10. Five years after treatment, the cure rate was identical in both groups 85 and 86 percent respectively.

Long term side effects, however, were less with seeds alone, 7 percent versus 12 percent in the men receiving the combination. This trial shows that radiation added to seeds is unnecessary and more toxic than seed radiation given by itself.

Interpreting Data

What should you as a patient take away from this data?  Considering the 3 categories of prostate cancer, for those who fit the profile, active surveillance is overall the best initial step for men with low-risk disease. It has the least side effects and the same mortality outcome as those who choose surgery or radiation. Now that we have an accurate way to scan these men for high-grade disease with multi-parametric MRI, active surveillance becomes an even more attractive option.

Men with intermediate and high risk prostate cancer should be treated with a seed implant. The need for supplemental beam radiation should be seriously questioned. Now with credible data to support these less invasive approaches, both the uncertainty and consternation surrounding treatment selection can be greatly alleviated.

Sources:

American Cancer Society. Survival Rates for Prostate Cancer

Cooperberg MR. Long-term active surveillance for prostate cancer: answers and questions. J Clin Oncol. 2015;33(3):238-40.

Hamdy FC, Donovan JL, Lane JA, et al. 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. N Engl J Med. 2016.

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