Given that a priority of the medical profession is to alleviate pain, it is incumbent upon its practitioners to avoid using emotionally-laden terminology that causes just which it wishes to avoid, i.e., pain. The terms “cancer,” “malignancy,” and “tumor” and are firmly entrenched in our common socio-political vocabulary. Bringing one of these terms to consciousness has the effect of conjuring up a lethal adversary for which screening, early detection, and opposition with specific treatment is mandated.
However it has been increasingly clear for the past several years that most patients who are presently diagnosed with one of the above terms in relation to their prostate are at risk of treatment for which the cost in side-effects far outweighs any benefit of aggressive treatment.
The incidence of prostate cancer is presently four to five times its mortality. Sixteen percent of men will be diagnosed with CaP but only three percent will succumb to it. As both non-invasive (PCA3, TMPRSS-ERG) and invasive diagnostic advances (increasing number of biopsies per case followed by “triple” immunohistochemical stains) magnify our ability to detect abnormalities in an aging population, we will only increase the fear which leads patients and their physicians to make poor choices.
It is time to reconcile the discrepancy of the term that pathologists assign to a microscopic finding to the historical and practical significance of that term. The most common significant finding made by contemporary pathologists on prostate biopsies cannot be adequately described by “tumor” (Greek: swelling), “cancer” (from the crab-like extension), or “malignant” (threatening to life or tending to metastasize). I propose the terms “prostatic tubular neogenesis” (creation of new epithelial tubes or acini) and “potentially malignant” to better describe the microscopic findings that we have in the past labeled “adenocarcinoma” “cancer” “tumor” and “malignant.”
The pathologist discovering an abnormality perhaps only fractions of millimeters in length and present on a small fraction of prostate cores may indeed have uncovered evidence representing the tip of a much larger, more aggressive process. While even the smallest abnormal finding on biopsy may be an indicator of a much larger and possible life threatening process, it is more often an incidental findng that is best surveilled or ignored rather than aggressively extirpated. Although attempts to identify “clinically insignificant” prostate cancers have been attempted, the sampling error inherent in the biopsy procedure has precluded practical application. While small lesions lacking histological aggressiveness may indeed be “potentially insignificant” the indolent nature of their status cannot be proven until after a prostatectomy. A diagnosis of “adenocarcinoma” or “cancer” once issued on a pathology report and communicated by the urologist or patient and his family is never “insignificant.”
Criteria are evolving that allow for the active surveillance of the common microscopic neoplastic findings we identify. As these histological criteria (presently the number or fraction of involved cores, the length of the focus, the present of Gleason pattern 4 or 5) and increasingly molecular criteria (TMPRSS-ERG, hCAP-D3, AZGP1) evolve, we will better define which of our findings are potentially life threatening and which are indolent. Other factors such as patient’s comorbity, age, family history, genotype, and psychological biases will undoubtedly assist in the decision as to what course of action, if any, is in the patient best interest.
I suggest that the terms “cancer,” “adenocarcinoma,” “malignancy,” and “tumor” be avoided by on pathology reports unless there exists clear evidence of Gleason pattern 4, more than two cores are involved, or if total lesion length is more than 3mm. The term “tubular neogenesis” followed by an explanation, can better serve the discussion between physician and patient that must follow. As our understanding evolves, criteria for identifying life-threatening prostatic alterations on needle core biopsies in conjuction with serological or urine-based molecular assays, or new non-invasing imaging techniques will allow the more aggressive terms to be used without fear of inducing unnecessary medical intervention.
It is my hope that such a change in terminology may better serve our patients by fostering the educational discussions they must have with their doctors as they decide upon a course of action acceptable to both patient and clinician. We must continue to investigate the histologic and molecular prognostic variables that will be useful in separating out the minority of life-threatening prostatic neoplasms from the majority of indolent ones. In the meantime, let us see that our diagnoses are placed in context so that we are not accomplices in advising therapies that are worse than the disease. Primum non nocere.
Sunday, February 10, 2008
Not HOW but WHETHER to be treated at all
The inflection point has been reached. For the vast majority of men with a recent diagnosis of prostate cancer the most important question is not what treatment is needed, but whether any treatment at all is required. Active surveillance is the logical choice for most men (and the families that love them) to make.
Thursday, February 7, 2008
NY Times Article: We dont know squat
February 5, 2008, 11:07 am
No Answers for Men With Prostate Cancer
Last year, 218,000 men were diagnosed with prostate cancer, but nobody can tell them what type of treatment is most likely to save their life.
Those are the findings of a troubling new report from the Agency for Healthcare Research and Quality, which analyzed hundreds of studies in an effort to advise men about the best treatments for prostate cancer. The report compared the effectiveness and risks of eight prostate cancer treatments, ranging from prostate removal to radioactive implants to no treatment at all. None of the studies provided definitive answers. Surprisingly, no treatment emerged as superior to doing nothing at all.
“When it comes to prostate cancer, we have much to learn about which treatments work best,'’ said agency director Carolyn M. Clancy. “Patients should be informed about the benefits and harms of treatment options.”
But the study, published online in the Annals of Internal Medicine, gives men very little guidance. Prostate cancer is typically a slow-growing cancer, and many men can live with it for years, often dying of another cause. But some men have aggressive prostate cancers, and last year 27,050 men died from the disease. The lifetime risk of being diagnosed with prostate cancer has nearly doubled to 20 percent since the late 1980s, due mostly to expanded use of the prostate-specific antigen, or P.S.A., blood test. But the risk of dying of prostate cancer remains about 3 percent. “Considerable overdetection and overtreatment may exist,'’ an agency press release stated.
The agency review is based on analysis of 592 published articles of various treatment strategies. The studies looked at treatments that use rapid freezing and thawing (cryotherapy); minimally invasive surgery (laparoscopic or robotic-assisted radical prostatectomy); testicle removal or hormone therapy (androgen deprivation therapy); and high-intensity ultrasound or radiation therapy. The study also evaluated research on “watchful waiting,'’ which means monitoring the cancer and initiating treatment only if it appears the disease is progressing.
No one treatment emerged as the best option for prolonging life. And it was impossible to determine whether one treatment had fewer or less severe side effects.
Many of the treatments now in widespread use have never been evaluated in randomized controlled trials. In the research that is available, the characteristics of the men studied varied widely. And investigators used different definitions and methods, making reliable comparisons across studies impossible.
“Investigators’ definitions of adverse events and criteria to define event severity varied widely,'’ the report notes. “We could not derive precise estimates of specific adverse events for each treatment.'’
The report findings highlighted by the agency include:
All active treatments cause health problems, primarily urinary incontinence, bowel problems and erectile dysfunction. The chances of bowel problems or sexual dysfunction are similar for surgery and external radiation. Leaking of urine is at least six times more likely among surgery patients than those treated by external radiation. Urinary leakage that occurs daily or more often was more common in men undergoing radical prostatectomy (35 percent) than external-beam radiation therapy (12 percent) or androgen deprivation (11 percent). Those were the findings of the 2003 Prostate Cancer Outcomes Study, a large, nationally representative survey of men with early prostate cancer. External-beam radiation therapy and androgen deprivation were each associated with a higher frequency of bowel urgency (3 percent) compared with radical prostatectomy (1 percent), according to the 2003 report. Inability to attain an erection was higher in men undergoing active intervention, especially androgen deprivation (86 percent) or radical prostatectomy (58 percent) than in men receiving watchful waiting (33 percent), according to the 2003 report. One study showed that men who choose surgery over watchful waiting are less likely to die or have their cancer spread, but another study found no difference in survival between surgery and watchful waiting. The benefit, if any, appears to be limited to men under 65. However, few patients in the study had cancer detected through P.S.A. tests. As a result, it’s not clear if the results are applicable to the majority of men diagnosed with the disease. Adding hormone therapy prior to prostate removal does not improve survival or decrease recurrence rates, but it does increase the chance of adverse events. Combining radiation with hormone therapy may decrease mortality. But compared with radiation treatment alone, the combination increases the chances of impotence and abnormal breast development. The most obvious trend identified in the complicated report is how little quality research exists for prostate cancer, despite the fact that it is the most diagnosed cancer in the country.
Studies comparing brachytherapy, radical prostatectomy, external-beam radiation therapy or cryotherapy were discontinued because of poor recruitment. Two ongoing trials, one in the United States and one in Britain, are evaluating surgery and radiation treatments compared with watchful waiting in men with early cancer. Other studies in progress or development include cryotherapy versus external-beam radiation and a trial evaluating radical prostatectomy versus watchful waiting.
“Successful completion of these studies is needed to provide accurate assessment of the comparative effectiveness and harms of therapies for localized prostate cancers,” the study authors said.
No Answers for Men With Prostate Cancer
Last year, 218,000 men were diagnosed with prostate cancer, but nobody can tell them what type of treatment is most likely to save their life.
Those are the findings of a troubling new report from the Agency for Healthcare Research and Quality, which analyzed hundreds of studies in an effort to advise men about the best treatments for prostate cancer. The report compared the effectiveness and risks of eight prostate cancer treatments, ranging from prostate removal to radioactive implants to no treatment at all. None of the studies provided definitive answers. Surprisingly, no treatment emerged as superior to doing nothing at all.
“When it comes to prostate cancer, we have much to learn about which treatments work best,'’ said agency director Carolyn M. Clancy. “Patients should be informed about the benefits and harms of treatment options.”
But the study, published online in the Annals of Internal Medicine, gives men very little guidance. Prostate cancer is typically a slow-growing cancer, and many men can live with it for years, often dying of another cause. But some men have aggressive prostate cancers, and last year 27,050 men died from the disease. The lifetime risk of being diagnosed with prostate cancer has nearly doubled to 20 percent since the late 1980s, due mostly to expanded use of the prostate-specific antigen, or P.S.A., blood test. But the risk of dying of prostate cancer remains about 3 percent. “Considerable overdetection and overtreatment may exist,'’ an agency press release stated.
The agency review is based on analysis of 592 published articles of various treatment strategies. The studies looked at treatments that use rapid freezing and thawing (cryotherapy); minimally invasive surgery (laparoscopic or robotic-assisted radical prostatectomy); testicle removal or hormone therapy (androgen deprivation therapy); and high-intensity ultrasound or radiation therapy. The study also evaluated research on “watchful waiting,'’ which means monitoring the cancer and initiating treatment only if it appears the disease is progressing.
No one treatment emerged as the best option for prolonging life. And it was impossible to determine whether one treatment had fewer or less severe side effects.
Many of the treatments now in widespread use have never been evaluated in randomized controlled trials. In the research that is available, the characteristics of the men studied varied widely. And investigators used different definitions and methods, making reliable comparisons across studies impossible.
“Investigators’ definitions of adverse events and criteria to define event severity varied widely,'’ the report notes. “We could not derive precise estimates of specific adverse events for each treatment.'’
The report findings highlighted by the agency include:
All active treatments cause health problems, primarily urinary incontinence, bowel problems and erectile dysfunction. The chances of bowel problems or sexual dysfunction are similar for surgery and external radiation. Leaking of urine is at least six times more likely among surgery patients than those treated by external radiation. Urinary leakage that occurs daily or more often was more common in men undergoing radical prostatectomy (35 percent) than external-beam radiation therapy (12 percent) or androgen deprivation (11 percent). Those were the findings of the 2003 Prostate Cancer Outcomes Study, a large, nationally representative survey of men with early prostate cancer. External-beam radiation therapy and androgen deprivation were each associated with a higher frequency of bowel urgency (3 percent) compared with radical prostatectomy (1 percent), according to the 2003 report. Inability to attain an erection was higher in men undergoing active intervention, especially androgen deprivation (86 percent) or radical prostatectomy (58 percent) than in men receiving watchful waiting (33 percent), according to the 2003 report. One study showed that men who choose surgery over watchful waiting are less likely to die or have their cancer spread, but another study found no difference in survival between surgery and watchful waiting. The benefit, if any, appears to be limited to men under 65. However, few patients in the study had cancer detected through P.S.A. tests. As a result, it’s not clear if the results are applicable to the majority of men diagnosed with the disease. Adding hormone therapy prior to prostate removal does not improve survival or decrease recurrence rates, but it does increase the chance of adverse events. Combining radiation with hormone therapy may decrease mortality. But compared with radiation treatment alone, the combination increases the chances of impotence and abnormal breast development. The most obvious trend identified in the complicated report is how little quality research exists for prostate cancer, despite the fact that it is the most diagnosed cancer in the country.
Studies comparing brachytherapy, radical prostatectomy, external-beam radiation therapy or cryotherapy were discontinued because of poor recruitment. Two ongoing trials, one in the United States and one in Britain, are evaluating surgery and radiation treatments compared with watchful waiting in men with early cancer. Other studies in progress or development include cryotherapy versus external-beam radiation and a trial evaluating radical prostatectomy versus watchful waiting.
“Successful completion of these studies is needed to provide accurate assessment of the comparative effectiveness and harms of therapies for localized prostate cancers,” the study authors said.
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