篩檢發現的乳癌有三分之一是過度診斷、過度治療


  July 14, 2009 — 公立機構篩檢計畫發現的乳癌,有三分之一是過度診斷,而過度治療比率也相去不遠。上述是根據針對加拿大、澳洲、挪威、瑞典、英國等國之篩檢計畫進行的統合分析,線上登載於7月9日BMJ期刊。
  
  這篇新分析是另一個增添乳房攝影之利弊爭論的研究,其中即包括了過度診斷與過度治療。
  
  Gilbert Welch醫師在對這篇新分析的編輯評論中寫道,問題不在於是否發生過度診斷,而是其發生頻率為何。
  
  Dartmouth醫學院醫學教授Welch醫師解釋,癌症過度診斷意指癌症病程緩慢,而病患在其產生癌症症狀之前即死於其他原因,或者癌症本身未持續惡化甚至復原。
  
  Welch醫師表示,過度診斷在前列腺癌篩檢上是廣泛認知的問題。
  
  他指出,至於乳癌,有越來越多和這個新研究一樣的有關過度診斷的證據。
  
  換言之,現在有五篇觀察研究指出,篩檢式乳房攝影與篩檢年齡之婦女的乳癌發生率增加有關,但是Welch醫師指出,較年長婦女的發生率幾乎並未隨之降低。
  
  不過,篩檢偵測癌症真的高達三分之一是過度診斷嗎?
  
  Welch醫師表示,迄今有關過度診斷的最有力證據,來自稍早的一篇有關乳房攝影和觀察方式進行比較的隨機控制試驗(BMJ. 2006;332:689-692)。Welch醫師指出,該研究中,篩檢時的過度診斷比率約為六分之一。
  
  不論過度診斷比率為何,兩篇研究的作者和編輯都同意,過度治療的比率幾乎都相去不遠。
  
  研究作者、丹麥哥本哈根Nordic Cochrane中心的Karsten Juhl Jorgensen醫師和Peter C Gotzsche醫師寫道,分辨致命和無害的癌症幾乎是不可能的,所有偵測到的癌症都得要治療。
  
  【危急關頭】
  Welch醫師指出,乳房攝影利弊之間的平衡,可以說是醫療上的危急關頭,這在過去一年受到相當多的注意。
  
  在英國,乳癌篩檢的公共衛生手冊中,普遍認為有關乳房攝影之傷害的資訊相當缺乏。如同Medscape Oncology所報導的,此一抗議聲浪導致手冊重寫。
  
  再者,紐約時報與其他媒體以頭版報導的一個2008年挪威研究的結論指出,約有20%篩檢偵測的侵犯性乳癌自發性恢復。挪威的研究者之一向Medscape Oncology表示,這類病灶是偽癌症。
  
  Welsh醫師認為,決定是否進行篩檢時,婦女們或許比較在意避免死於乳癌之人數與過度癌症診斷人數之間的差異。
  
  為了提供醫師和病患們有關乳房攝影的利弊清單,Welch醫師列出他所編輯的一張表格。利弊雙方表示於50多歲開始接受年度乳房攝影之每1,000名婦女的事件發生比率。
  
  

1 名婦女可以避免死於乳癌

2–10 名婦女會被過度診斷,以及不必要的治療

10–15 名婦女會被告知,她們比原本預期的年紀更早罹患乳癌,但這不會影響其預後

100–500 名婦女會有至少 1 種假警報 ( 其中約半數會接受切片 )


  
  【
  新研究的細節】
  為了評估有組織之篩檢計畫中的過度診斷量,丹麥的研究者比較了英國、加拿大曼尼托巴、澳洲新南威爾斯、瑞典、挪威部份地區等地進行這類計畫前後的乳癌發生率傾向。
  
  作者寫道,此一方法的理由是根據下述觀念,如果篩檢有效且不會發生過度診斷,那麼篩檢年紀時癌症的初步增加,應和不再接受篩檢的年長組的降低比率完全互補。何以如此呢?作者解釋,因為年長組的癌症將可在年輕時因為篩檢而偵測。
  
  作者們也指出,這類方法應將乳癌背景發生率和其他因素納入考量。
  
  一組資料提供進行此分析的範例。在瑞典,全國篩檢始於1986年,而在1998年時,幾乎所有適合的婦女都接受篩檢。在2000年時,篩檢後侵犯性乳癌的比率,在50至59歲婦女,比預期的增加54%,在60至69歲婦女中,增加21%。而70至84歲婦女乳癌發生率降低,但是作者寫道,發生率接近預期的比率。簡而言之,年輕婦女的增加有88%並未在年長婦女中互補性降低。
  
  總之,在各國的多種公共篩檢計畫中,包括管狀原位癌的乳癌整體過度診斷比率為52%。侵犯性乳癌的過度診斷比率為35%。
  
  作者宣告沒有相關財務關係。
  

1 in 3 Breast Cancers Detected by Screening is Overdiagnosed, Overtreated

By Nick Mulcahy
Medscape Medical News

July 14, 2009 — One in 3 breast cancers detected in publicly organized screening programs is overdiagnosed. And overtreatment inevitably occurs at the same rate, according to a meta-analysis of screening programs in Canada, Australia, Norway, Sweden, and the United Kingdom, published online July 9 in BMJ.

The new analysis is yet another study that adds to the controversy surrounding mammography's benefits and harms, which include overdiagnosis and overtreatment.

"The question is no longer whether overdiagnosis occurs, but how often it occurs," writes Gilbert Welch, MD, in an editorial accompanying the newly published analysis.

Overdiagnosis of cancer refers to cancers that grow so slowly that the patient dies of other causes before it produces symptoms or to cancer that is dormant or even regresses, explained Dr. Welch, who is a professor of medicine at Dartmouth Medical School in Hanover, New Hampshire.

Overdiagnosis is a "widely recognized problem" in prostate cancer screening, said Dr. Welch.

With regard to breast cancer, there is a growing body of evidence about overdiagnosis with which the new study is consistent, he added.

Namely, there are now 5 observational studies that indicate screening mammography is associated with increases in the incidence of breast cancer in women of screening age, but that there is "little or no subsequent decrease in the incidence of older women," notes Dr. Welch.

But is the rate of overdiagnosis really as high as 1 in 3 screen-detected cancers?

Dr. Welch says that that the "most compelling evidence to date" about overdiagnosis comes from an earlier randomized controlled trial of mammography versus observation (BMJ. 2006;332:689-692). In that study, overdiagnosis from screening occurred at a rate of 1 in 6, Dr. Welch notes.

Whatever the rate of overdiagnosis, both the study authors and the editorialist agree, overtreatment is likely to occur at the same rate.

"As it is not possible to distinguish between lethal and harmless cancers, all detected cancers are treated," write the study authors, Karsten Juhl Jorgensen, MD, and Peter C Gotzsche, MD, from the Nordic Cochrane Center in Copenhagen, Denmark.

Close Call

The balance between the benefits and harms of mammography make it one of medicine's "close calls," adds Dr. Welch. It is a close call that has received a lot of public attention in the past year.

In the United Kingdom, there was public outcry over the lack of information about the harms of mammography in a public-health pamphlet about breast cancer screening. The protest led to a rewrite of the pamphlet, as reported by Medscape Oncology.

Furthermore, The New York Times and other media made front-page news out of a 2008 study from Norway that concluded that about 20% of screen-detected invasive breast cancers spontaneously regress. One of the Norwegian researchers told Medscape Oncology that such lesions are "pseudo-cancers."

In making decisions about whether or not to get screened, women are probably most interested in the "trade-off between the number of deaths from breast cancer avoided and the number of cancers overdiagnosed," suggested Dr. Welsh.

In an effort to provide physicians and their patients with a "balance sheet" of the harms and benefits of mammography, Dr. Welch included a tabular display along with his editorial. The credits and debits are for every 1000 women undergoing annual mammography for 10 years starting at the age of 50 years.

Credits Debits
1 woman will avoid dying from breast cancer

?

2–10 women will be overdiagnosed and treated needlessly

10–15 women will be told they have breast cancer earlier than they would otherwise have been told, but this will not affect their prognosis

100–500 women will have at least 1 "false alarm" (about half these women will undergo biopsy)

New Study Details

To estimate the extent of overdiagnosis in organized screening programs, the Danish investigators compared trends in breast cancer incidence before and after the screening was initiated in the United Kingdom; Manitoba, Canada; New South Wales, Australia; Sweden; and parts of Norway.

The reason for this approach is based on the idea that, if screening was effective and did not produce overdiagnosis, then "the initial increase in cancers in the screened age groups would be fully compensated for by a similar decrease in the older age groups no longer offered screening," write the authors. Why is this so? Because the cancers in the older age groups would have been detected earlier on in life, as a result of screening, explain the authors.

The authors also note that such an approach must take into account changes in the background incidence of breast cancer and other factors.

One set of data offers an example of how the analysis was conducted. In Sweden, nationwide screening began in 1986, and in 1998, "almost all eligible women had been offered screening," the authors write. In 2000, the increase in invasive cancer after screening was implemented was 54% above expected rates for women aged 50 to 59 years and 21% for women aged 60 to 69 years. A drop in the incidence of breast cancer occurred among women aged 70 to 84 years, but the incidence "approached the expected rate," write the authors. In short, 88% of the increase among younger women was not compensated for by any drop in the older women, note the authors.

In summary, the total overdiagnosis of breast cancers, including ductal carcinoma in situ, from these public screening programs in different countries was 52%. The overdiagnosis of invasive breast cancer was 35%, report the authors.

The authors have disclosed no relevant financial relationships.

BMJ. 2009;339:b1425 and b2587.

    
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