Selecting the Best Therapy for Newly-Diagnosed Prostate Cancer

Active Surveillance, Surgery, or Radiation? What the Studies Say

People Walking on the Street

Due to the absence of well-designed comparative studies, treatment selection for prostate cancer has been highly controversial. However, in October 2016, two landmark articles published in the New England Journal of Medicine reporting 10-year results from 1,643 bold volunteers who allowed themselves to be randomly allocated (akin to “drawing straws”) to treatment with either surgery, radiation or active surveillance.

The first study compared 10-year survival outcomes, while the second, companion study, used questionnaires to compare the quality-of-life outcome. First, we will discuss the survival question. Then we will discuss the quality of life implications.

The Importance of Study Design

Finding volunteers to participate in a randomly allocated therapy, rather than choosing treatment themselves, is hard to accomplish. It’s no surprise that this is the only study ever published of this type. Nevertheless, randomization is essential to ensure that patients in each of the three groups are equally healthy and have an equivalent type of prostate cancer. Without an assurance of parity between the groups, the study results would be untrustworthy. 

Comparing Yourself to the Study

The main value of a randomized study is that newly-diagnosed cancer patients can get accurate information about how the three most common treatment approaches compare. However, to make accurate comparisons, a patient’s profile must be similar to the patients who participated in the study. So, let’s review the profile of the study participants. Their ages ranged from 50 to 69, with the average age being 62. The average PSA was 4.6. In one-fourth of the men, the doctor could feel a nodule on the prostate with his finger. Nine out of ten of the men had PSA levels less than ten (although there were a few patients with PSA levels between 10 and 20). Three-fourths of the men had Gleason 3 + 3 = 6., one-fifth had Gleason 7, and one out of fifty of the men had Gleason scores of 8 to 10.

Monitoring With Active Surveillance

Monitoring anything called “cancer” sits poorly with patients and doctors alike. It is a fairly new idea and the methodology is still evolving. The monitoring method in this study relied almost exclusively on PSA. The use of follow-up biopsies or imaging with multiparametric MRI was not recommended which is unusual by today’s standards. Over the 10 years of the study, almost half of the men in the surveillance group had surgery or radiation which is not unusual. The basic philosophy behind active surveillance is to watch men closely, and if the cancer grows, apply curative treatment before the cancer spreads.

The Impact of Treatment on Survival

The primary design of the study was to answer one question—survival.When men first hear that they have cancer, most are consumed with thoughts about how to avoid early mortality. If survival is the priority, this study clearly reports that treatment approach makes no difference. In all three groups, the result was the same. Only 1 percent of the men (a total of 17 men) died from prostate cancer within the first 10 years. This figure is even lower if we consider what the outcome would have been if the men with Gleason 7 and / or a palpable nodule were excluded from the study. In the first 10 years, there were only six deaths in men with Gleason 6 and a normal rectal exam (the six men were equally distributed across the three groups). The impact of treatment on mortality, at least during the first 10 years, appears irrelevant. 

What About Metastases?

But what about after 10 years? This is not a super high priority question in men who are pushing 70; men in their 80s are more likely to die from unrelated causes. But it’s certainly a relevant question for men who are in their 50s. The study does report a slightly higher risk of developing metastases for the group of men who were on surveillance compared to immediate surgery or radiation. Specifically, only 29 men, 13 who had surgery and 16 who had radiation, were living with metastases after 10 years; whereas 33 men on surveillance had metastases. This calculates out to a 3 percent higher risk of metastases with surveillance compared to immediate surgery or radiation. Not a very big difference, but certainly consequential if you are one of the unlucky men in the 3 percent.

The Impact of Metastases on Survival

Since at least 50 percent of men who develop metastases will eventually die from prostate cancer, it appears, according to this study, that men who are treated with active surveillance will have a slightly higher mortality rate (perhaps 1 to 2 percent higher) that will occur from 10 to 20 years after diagnosis, compared to the men who undergo immediate surgery or radiation. However, this fact should be taken with a major grain of salt, considering that the surveillance techniques used were inadequate by modern standards. As noted above, the men were only watched with PSA. They had no regular scanning with multiparametric MRI, nor were any screening random biopsies performed on a scheduled basis. These patients were left pretty much to fend for themselves. Considering this astonishing level of neglect, an increased metastases rate of only 3 percent actually seems rather low.

Surveillance Technology Has Dramatically Improved

There is another compelling reason to believe that the higher metastasis rate reported in this study overestimates the danger of doing active surveillance. The profile of the men who were admitted into this study is not typical of the type of men who are normally recommended for active surveillance. Over a fourth of the men in this study had a Gleason scores of 7 or above, a palpable nodule detected on digital rectal examination of their prostate, or both. This is a much more aggressive type of cancer profile than what is usually advised for monitoring.

Technological Improvements With Surgery or Radiation?

Before we leave our discussion of survival and move on to the discussion of quality of life, I have one further observation to offer. I criticized the study’s methodology by relying on PSA monitoring alone as inadequate. But what about the techniques for surgery or radiation? Would we expect a higher cure rate using 2016 technology compared to what the men in this study received? The short answer is no. Although studies of robotic surgery report faster healing, the cure rates and the rates of sexual and urinary recovery have not improved. With regards to the external beam radiation, cure rates and side effects with modern IMRT are in the same range.

Quality of Life Matters if Survival Is the Same

The pursuit of active surveillance only makes sense when interpreted through a quality of life perspective. The only reason to forgo curative treatment is the well-founded concern that normal sexual and urinary function will be seriously impaired. If treatment had no side effects, everyone could have treatment; men could move on with their lives and forget about monitoring beyond a periodic PSA check. However, let’s address the most common treatment-related problems, the risk of impotence and incontinence.

Questionnaires Before and After Treatment

In the companion study evaluating quality of life, all participants were questioned about their sexual function and urinary control prior to treatment, 6 and 12 months after treatment, and annually thereafter. In this comparison, surgery was easily identified as the worst option from a quality of life standpoint. Prior to treatment, only 1 percent of men had urinary incontinence and needed absorbent pads. But that increased to 46 percent 6 months after surgery and slowly improved to 17 percent 6 years later. Six years after radiation on the other hand, only 4 percent of the men required a pad. Eight percent of the men on surveillance required a pad (remember that close to 50 percent men on active surveillance underwent delayed surgery or radiation).

The Impact of Treatment on Sexual Function

I think the most concise way to communicate the study findings on sexual function/impact is to provide you with a direct quote from the study:

“At baseline, 67 percent of men reported erections firm enough for intercourse but by 6 months that fell to 52 percent in the active-monitoring group, to 22 percent in the radiation group and to 12 percent in the surgery group. Erectile function remained worse in the surgery group at all time points, and although there was some recovery to 21 percent at 3 years, this rate declined again to 17 percent at 6 years. The rate at 6 years for the radiation group was 27 percent. The rate in the active monitoring group was 41 percent at 3 years and 30 percent at year 6.” 

While there will be an inevitable decline in sexual function over time in these relatively elderly men, results still show that surgery has a far bigger negative impact than either radiation or active surveillance. As pointed out in the study, a third of the men in this age group are already impotent prior to treatment. Since previously impotent men cannot be made more impotent with radiation, and other serious side effects were rare, there seems to be little motivation to avoid radiation in the subgroup of men who have preexisting impotence.

Conclusions from These Two Landmark Studies

First, survival rates with active surveillance are equal to immediate surgery or radiation out to 10 years. To ensure safety and survival rates beyond 10 years, men contemplating active surveillance should rule out the presence of any Gleason grade disease of 7 or above with a multiparametric MRI at baseline followed by annual scans. Second, survival rates with radiation are equivalent to surgery but with far fewer urinary and sexual side effects. Apart from its sexual side effects, radiation is remarkably well-tolerated. If treatment is deemed necessary, radiation is a much better way to treat prostate cancer than with surgery.

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