March, 2013

Sighs and Symptoms

By Michael J. Katin, MD

In the politically-correct 20teens, it has become troublesome to advocate aggressive courses of treatment with substantial morbidity and even mortality. Gone are the times in which the desire of the patient was to do everything possible to wipe out the disease regardless of the desperate measures required. The goal is now to maximize quality of life rather than control of cancer, and it is a wonderful occurrence when both can be accomplished.

The irony is that this philosophy seem to apply only to cancer treatment but not to pretty much everything in our lives. Our economy would be booming if oil, gas, and coal were optimally exploited, but potential real and speculative long-term effects on our physical health and well-being are now being emphasized rather than our short-term financial health. Children will be much happier if allowed to indulge in Big Macs, Cheetos, and Mountain Dew and these joys are being taken away because of concern about the effects of their being obese in the future. Ironically, one habit that cuts down on weight gain is cigarette smoking, but that benefit seems to be considered irrelevant. Once again, the short-term pleasure achieved by smokers is thought not to be worth the long-term effects.

Despite all this, oncologists are now expected to come up with treatments for cancer that cause minimal disruption in the short term rather than maximally reducing the risk of recurrence in the long term. Since we are being held to a different standard, quality of life assessments are now being considered just as important as treatment outcomes. An entire industry is evolving dedicated to studying effects of treatment rather than to maximizing the effectiveness of treatment.

This then leads to the question of treatment for prostate cancer. Prostate cancer is the second-leading killer of men in the United States ( 29,720 estimated in 2013 ) and is responsible for more than 258,000 deaths worldwide (2008 data ). Prostate cancer can be detected early with screening, and there is an ongoing controversy as to whether this is really worth it in the long run. Those without prostate cancer claim that a large number of men will die from other causes before dying of prostate cancer, which is like saying it's ok to drive without a seat belt since you will probably die from something other than an automobile accident. Regardless, there is more discussion regarding the type of treatment and, in fact, whether treatment should be given at all, than research on increasing the cure rate.

If we can't make the rules, we might as well play by the rules. All of which brings us to the landmark publication by Resnick et al. from the New England Journal of Medicine from January 31, 2013. A colleague (not an oncologist) expressed that this paper proved that "radiation therapy is as good as radical prostatectomy and has fewer side effects" and concluded that the debate was now over as to which treatment was better. I appreciated that he had reached this conclusion, even though it doesn't follow from the article. No doubt he was not the only person coming to this conclusion and maybe I should just be happy about it, as a radiation oncologist, but in the spirit of accuracy it is necessary to make a few points.

This was a truly ambitious work and I do not mean to downplay the effort that went into this, but it shows the problems with analyzing results over years from multiple different origins. Twelve authors participated in this, produced by the Center for Surgical Quality and Outcomes Research from Vanderbilt University. Six SEER (Surveillance, Epidemiology, and End Results) sites contributed 11,137 eligible cases of men treated for prostate cancer. Of these, only 5,672 were sampled, with over-sampling of men under age 60 and Hispanic and black men in some of the registries. This number decreased to 3,533 when it included only men who had filled out a survey and 6 months, 12 months, or both after diagnosis. This was then decreased to 1,655 men who had been diagnosed between the ages of 55 and 74, had completed either a 2-year or 5-year survey, and who had been treated with prostatectomy or radiation therapy with or without hormonal manipulation. Of these, 1,164 men had been treated with prostatectomy and 491 with radiation therapy. The initial enrollment had been performed between October 1, 1994, and October 31, 1995, and men were then contacted at 1, 2, 5, and 15 years after diagnosis to fill out a survey on clinical outcomes and health-related quality of life specific for this condition. Unfortunately, by 15 years 569 of these 1,655 had died! This therefore left a grand total of 1,086 of the original 11,137 patients, or 9.1 per cent, to be analyzed at 15 years.

This probably should not be taken to be the last word on long-term effects of surgery or radiation therapy considering the fact that a small number of patients remained at the end and that, in fact, these had already gone through a selection process, not to mention that they came from six SEER groups rather than the entire country. This also presupposes that they very accurately answered the quality of life questionnaires, recognizing that people can be more or less emphatic about reporting symptoms. The results are both good and bad in terms of our expectations. My colleague was correct in saying that the paper reported similar sequellae in the long run and generally better ones in the short term, thus implying that radiation therapy may be just as good with less morbidity, but it first needs to be recognized that techniques for both surgery and radiation therapy have changed markedly since the mid-1990s and, although interesting for historical value, the findings might not be pertinent to today's treatment methods. This publication reported that in the short term, radiation therapy had the advantage in terms of producing fewer problems with incontinence and impotence but more problems with rectal urgency. Interestingly, these differences all seemed to vanish by 15 years after treatment. Was this due to the nature of the men who were able to survive prostate cancer as well as every other illness to be alive at 15 years?

This also, of course, assumes that men who are not treated with prostate cancer have no incidence of incontinence, impotence, or rectal urgency. In fact, in the publication by Johansson et al. regarding long-term quality of life after radical prostatectomy or watchful waiting, from the Scandinavian Prostate Cancer Group-4 randomized trial, published in Lancet Oncology in 2011, erectile dysfunction was reported in 80% of men in the watchful-waiting group and 46% in a control group, and urinary leakage was reported in 11% of men in the watchful-waiting group and 3% of men in a control group, compared to 84% and 41%, respectively in the radical prostatectomy group. The median followup was 12.2 years (7-17 years). Unfortunately, life itself is not without side-effects.

What can be done to better assess symptoms in cancer treatment if we are to try to come up with the treatment with the least impact? Even watchful waiting doesn't seem to do that well. Be reassured that there are investigators working on this. A report published in Cancer January 15, 2013, by Cleeland and 13 other authors, describes that ASCPRO (Assessing the Symptoms of Cancer Using Patient-Reported Outcomes) is hard at work at this. ASCPRO was established in 2006, with the goal of reviewing the use of symptom measures to facilitate the implementation of symptom assessment in clinical trial and clinical research outcomes. This goal was supported by a directive from the FDA (Food and Drug Administration ) to use PRO (patient-reported outcomes) for the purpose of improving HRQOL (Health-Related Quality of Life) assessments. ASCPRO then commissioned a MTF (Multisymptom Task Force) to address these methods, with the summary of their efforts described in the Cancer article. OMG!!!!

In the meantime, we'll continue to do our best to treat patients with personal attention to try to make their experience as minimally traumatic as possible, recognizing that eventually only treatments with no ill effects whatever (i.e., no treatments) will be allowed. A French revolutionary once said," On ne saurait faire une omelette sans casser des oeufs." In contrast, we must assure that no eggs will be harmed in the making of our treatment plans.

Would humankind be better served if all efforts were dedicated to wiping out every last cancer cell rather than being concerned on the effects on the individual?