Two different views on a study showing that immediate treatment improves survival in PCa patients
For some men with localized prostate cancer, active surveillance has emerged in recent years as a viable management option. Defined as rigorous monitoring with the option of initiating potentially curative therapy should disease progress, this approach generally has been considered for patients with early, indolent disease (T1c or T2a tumors, a Gleason score of no more than 6, and a PSA level not greater than 10 ng/mL).
For patients older than 70 years, these criteria have sometimes been more relaxed. Clinicians often have told men under surveillance that their risk of death is virtually the same as it would be if they were treated immediately with surgery or radiation, with its potential complications, such as erectile dysfunction and urinary incontinence.
Then, in late 2006, researchers at the Fox Chase Cancer Center and the University of Pennsylvania, both in Philadelphia, published the results of a large observational study showing that men aged 65-80 who received prompt radical prostatectomy or radiation for localized prostate cancer had a 31% lower risk of dying than did surveillance pa-tients during 12 years of follow-up. The findings were published in the Journal of the American Medical Association (2006;296:2683-2693).
In an interview with Renal & Urology News, Yu-Ning Wong, MD, lead author of the study and a medical oncologist at Fox Chase, pointed out that these results do not mean that surveillance is always a bad idea. “Many men with comorbidities such as significant lung, cardiovascular or kidney disease should undergo active surveillance,” she said, “as should some men who are concerned, justifiably, about the side effects of active treatment.”
Dr. Wong said her study does suggest that prostate cancer management should be decided on a case-by-case basis, and that factors such as advancing age should not be used to rule out aggressive treatment. “It's a complicated decision, and until recently there was an absence of data showing that active treatment helps these patients,” she explained. “But patients are living longer and healthier these days, which enhances the potential benefit of active treatment.”
Other research, including a study at New York-Presbyterian/Weill Cornell Medical Center, has added fuel to the treatment-is-better fire. Published in the March 2007 Journal of Urology, this study found that patients with aggressive, non-metastatic prostate cancer (Gleason score 8-10) who received prostatectomy or radiation could expect to live twice as long—14 vs. 7 years—as patients under surveillance.
In light of these developments, we asked two well-known prostate cancer experts, Peter Scardino, MD, chairman of the department of surgery at Memorial Sloan-Kettering CancerCenter in New York, and Chris Parker, MD, senior lecturer and honorary consultant in clinical oncology at RoyalMarsdenHospital in Surrey, England, this question: “When, if ever, is active surveillance the right choice for patients with prostate cancer?” Their answers are below.
Dr. Scardino: Active surveillance (AS) is often a good choice. The right approach, in my view, is to be aggressive diagnostically but conservative therapeutically. When it comes to determining appropriate treatment, we must judge the seriousness of the cancer and its potential for metastasizing and eventually causing death, against the patient's age, overall health, and potential longevity. I have some patients in their 50s who are on AS. If, with biopsy and MRI, I can validate that their disease is contained and their PSA is stable, I feel comfortable watching them carefully. Maybe half of them will need treatment in five to seven years, and half of them will go 10-15 years before they need treatment.
But we must be cautious about being too conservative. Especially now, when many men are living into their 80s and 90s, it's possible to make a mistake by being less aggressive. We can never say with certainty that patients won't lose anything by waiting. We estimate that if a man waits before undergoing treatment, his chances of being cured drop 1% per year. Thus, if a man has a 95% chance of being cured today, in 10 years he will have an 85% chance of being cured. The alternative to cure may not be death; it may just mean the patient will need a second course of treatment. But you do take more of a chance by waiting.
Thanks to regular PSA screening, we're diagnosing more prostate cancers these days. Many of these are very small; some are so early that it's reasonable to look on them not as actual cancers but as histological in-dicators that early malignant changes are going on. What we have then is a problem with language; we call these areas ‘cancers,' and it scares people to death. As a result, many men want aggressive treatment when the benefits would actually be extremely small.
Radical surgery and radiation are great forms of treatment if a patient has prostate cancer that's posing a threat to his health. But for tiny, early cancer, you are trading your worry about a lesion that may never become a problem for the immediate complications of surgery or radiation. It's important to remember that even the best, most modern techniques of brachytherapy cause about 50% of men to become impotent over five years; radiation can also cause radiation proctitis, strictures, and long-term bowel problems. People also underestimate the morbidity factor of surgery.
Of course, when it comes to deciding on treatment, the patient's wishes must be taken into serious consideration. Some men to whom I strongly recommend treatment are not willing to undergo it. In that case, I keep them informed if the cancer is becoming more serious. On the other hand, if a patient insists on being treated, and if he fully understands the risks and benefits of treatment, it often makes sense to go ahead. We live in a society in which most people like to solve their problems; many doctors and patients think this way. There are also legal and financial reasons to treat aggressively. There is always the threat of lawsuits; if you put a patient on AS and his cancer metastasizes, you may be sued. Also, if you do radiation and surgery and bill insurance for it, you'll get paid. If you do AS, your compensation will be considerably lower. Of course, the patient must make the final decision, but I always tell patients not to base treatment decisions on how the options are framed by the first doctor they see. I think every patient should first seek another opinion from a doctor who will not benefit in any way from whatever treatment he selects. Over the next five to 10 years we will see a number of new technologies that will allow us to knock out a small amount of prostate tissue. This is focal therapy, and it will enable men with small, early cancers, who are uncomfortable with the idea of waiting, to be treated only at the area of abnormality. Currently, some doctors are treating half the lobe of the prostate with cryotherapy, although it's probably not an ideal tool because it affects the nerves on that side of the prostate. But new technologies are coming—such as high-intensity fo-cused ultrasound (HIFU), and photodynamic therapy. The technology I'm most excited about is MRI-guided HIFU. The FDA has already ap-proved a trial at Brigham & Women's Hospital in Boston that's using focused ultrasound for uterine fibroids. In the future, this will be used to treat breast, prostate, and other cancers.
Dr. Parker: I would turn the question around and ask, “Given the lack of evidence from randomized trials in localized, screen-detected low- and intermediate-risk prostate cancer, when, if ever, is immediate treatment an appropriate strategy?”
Most men with screen-detected prostate cancer do not need treatment. It's important to note that the JAMA study has a number of very important limitations. First, it was not randomized, so it's possible that any differences in outcome between the treatment groups relate to an imbalance in unknown but important prognostic factors. Second, the difference in overall mortality between the two groups was very small because a majority of deaths were from causes other than prostate cancer.
Active surveillance is for men for whom it is uncertain whether or not aggressive treatment is necessary. The aim is to target treatment to those who need it, and avoid treatment in those who do not. So, when it comes to patient selection for AS, we should identify men for whom delayed treatment, if it does become necessary, would be as effective as immediate treatment. We are not trying to identify only those men for whom treatment will never be needed. Men who will never need treatment don't need active surveillance.
It's important to point out that the morbidity of radical treatment for prostate cancer is well known. In my view, patients should weigh the known morbidity of treatment against the unknown potential for improved survival. If treatment had no morbidity, then treating all patients would make sense. At present, the morbidity of all radical treatment options remains significant, and active surveillance is therefore an attractive alternative. Ten years ago there was enough data to say that active surveillance makes sense as an approach to low-risk prostate cancer. Now we have data from AS, with 10-year follow-up, demonstrating that the results are satisfactory.
Ultimately, the choice between AS and immediate treatment is a value judgment. The advantage of AS is that most men will avoid the morbidity of treatment. The possible advantage of immediate treatment is that the patient might have better long-term survival. But this is not known. I have estimated that a 14-year treatment delay would probably increase prostate-cancer mortality just 7.5%. We'll have better data when the START (Standard Treatment Against Restricted Treatment) trial is completed—it is currently comparing these two approaches.
Of course, when it comes to determining treatment, the patient's values are of paramount importance. Only the patient knows how important it is to him to avoid impotence or incontinence. And only the patient can trade off the risk of side effects against the potential for improved survival. The doctor's role is to provide the best available information so that the pa-tient can make his judgment. If treatment had a 50% risk of impotence and a 2% improvement in 15-year overall survival, most men would choose not to have it.