#388 — 前列腺癌筛查：为何现行PSA指南未能保护男性，以及现代工具如何提升早期检测并挽救生命

大家好。

Hey, everyone.

欢迎收听《Drive》播客。

Welcome to the Drive podcast.

我是你们的主持人阿提亚。

I'm your host, Attia.

这个播客、我的网站，还有每周的通讯，核心目标都是把长寿科学变成人人都能看懂的内容。

This podcast, my website, and my weekly newsletter all focus on the goal of translating the science of longevity into something accessible for everyone.

我们致力于提供最优质的健康与养生内容，为此组建了一支很棒的分析团队来实现这个目标。

Our goal is to provide the best content in health and wellness, and we've established a great team of analysts to make this happen.

对我来说，最重要的是这些内容完全不靠付费广告来维持。

It is extremely important to me to provide all of this content without relying on paid ads.

能做到这一点，全靠我们的会员支持。

To do this, our work is made entirely possible by our members.

作为回报，我们会为会员提供独家内容和额外福利，这些都是免费用户享受不到的。

And in return, we offer exclusive member only content and benefits above and beyond what is available for free.

如果你想在这一领域深耕、提升自己的认知，我们承诺，会员从订阅中获得的价值，绝对远远超过订阅费本身。

If you want to take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of the subscription.

如果你想了解高级会员权益的更多细节，可以访问peterattiamd.com/subscribe。

If you want to learn more about the benefits of our premium membership, head over to peterattiamd.com/subscribe.

欢迎大家收听《Drive》的本期特别节目。

Welcome to a special episode of The Drive.

今天这期节目我会深入讲解一个主题：前列腺癌症筛查，这是我一直非常关注、也很在意的一个话题。

In this episode, I'm going to walk through a single topic in-depth, and this is prostate cancer screening, something that I'm very passionate about.

而且我们认为这期内容非常有公益价值，刚好提到了PSA这个词，我不是在玩双关啊，这期的完整正片和详细节目笔记会对所有人开放，不管你是不是会员都能看。

And because we consider this a really important PSA, no pun intended, the full episode and the detailed show notes for this discussion will be available to everyone regardless of whether or not you're a premium subscriber.

这期节目里，我会聊几个点：明明有早筛手段，为什么晚期、转移性前列腺癌的确诊案例还在不断增加？PSA到底测的是什么？为什么连续追踪这个数值，比只看一次的单独结果要有价值得多？

In this episode, I discuss why advanced and metastatic prostate cancer diagnoses are rising despite the availability of screening tools, What PSA actually measures and why it's more useful when interpreted over time than it is in a single one off number.

还有MRI、前列腺密度、PSA增速，以及更先进的活检技术，怎么能在查出更多侵袭性癌症的同时，减少不必要的过度检查；主动监测如何帮低风险前列腺癌患者避免过度治疗；为什么反对PSA筛查的那些研究依据漏洞百出；还有非那雄胺这类常用的防脱药物，如果医生和患者不上心，它会压低PSA数值，让人错过预警信号。

How MRI, density, PSA velocity, and improved biopsy techniques can reduce unnecessary procedures while improving the detection of aggressive cancers how active surveillance helps avoid overtreatment in men with low risk cancers why the evidence used to argue against PSA screening was deeply flawed How drugs like finasteride, which are commonly used to prevent hair loss, can suppress PSA and lead to missed warning signs if clinicians and patients are not vigilant.

最后我还会说，要是我们的目标之一是降低前列腺癌的死亡率，为什么定期做PSA检测这么重要。

And why I think regular PSA testing is so important if one of our objectives in life would be to eliminate prostate cancer mortality.

那么，不多说了，希望你们喜欢这期《The Drive》特别节目。

So, without further delay, I hope you enjoy this special episode of The Drive.

今天我想深入聊一个我特别在意的话题，一个我们在人群层面搞错了、而且已经实实在在夺走生命的问题。

Well, today I want to dig into something that I feel quite strongly about and something that I think we're getting wrong at the population level in a way that is measurably costing lives.

我们要谈的是前列腺癌筛查，特别是PSA检测，为什么我觉得现在的指南辜负了男性，以及在我看来，2026年及以后该怎么做才更合理。

We're going to talk about prostate cancer screening, specifically PSA testing, and why I believe the current guidelines have failed men, and obviously what I think a more modern approach to screening should look like in 2026 and beyond.

这个话题对任何听众都很重要——不管你可能是患者本人，是关心患者的人，还是医生。

This is really a discussion that I think is relevant for anybody listening to this as a potential patient, someone who cares about a patient, or whether you're a clinician.

在讨论快结束的时候，我还想聊聊另一个被严重低估、但极其危险的问题：一种叫非那雄胺的药。

I'm going to spend some time towards the end of this discussion on something that I also think is dangerously underappreciated, which is the interaction between a drug called finasteride.

这种药有数百万男性在服用，用来防脱发，但它会严重影响我们对PSA值的解读。

This is a drug that literally millions of men are taking for hair loss prevention, and how that drug interacts with our ability to interpret PSA correctly.

如果你在吃非那雄胺，而医生又不了解这玩意儿对PSA的影响，那你可能正坐在一颗定时炸弹上，却没人知道。

Because if you're on finasteride and your doctor doesn't understand the implications of that and how that impacts your PSA values, you could be sitting on a ticking time bomb without anybody knowing it.

先让我把背景铺垫一下。

Let me set the stage.

前列腺癌是男性第二大癌症死因，仅次于肺癌。

Prostate cancer is the second leading cause of cancer death in men, with only lung cancer claiming more lives.

大约每八个男性中就有一人会在一生中被诊断出前列腺癌，仅今年，就有大约三万六千名美国男性因此丧生。

About one in eight men will receive a prostate cancer diagnosis at some point in their lives, and this year alone, roughly thirty six thousand American men will die from it.

这种病让人既充满希望又特别无奈——早发现的话，预后简直好得惊人。

So, what makes this disease both uniquely hopeful and uniquely frustrating is that when you catch it early, the prognosis is outstanding.

从确诊开始算，十五年生存率接近百分之九十七。

So, we're talking about a fifteen year survival rate approaching ninety seven percent from first diagnosis.

我们现在有简单、普及度高、而且每年都在不断升级的筛查手段。

We have detection tools that are simple, widely available, and getting more sophisticated every year.

可偏偏，晚期前列腺癌的发病率却在持续上升。

Yet, here we are watching the rates of advanced stage prostate cancer climb.

没错。

That's right.

如今晚期前列腺癌的检出率，比十五年前还要高。

The rates at which advanced prostate cancers is showing up is higher today than it was fifteen years ago.

美国和加拿大最新的数据证实了泌尿科医生们多年来一直担心的问题。

Recent data out of both The United States and Canada confirm what many urologists have been warning about for years.

我们现在发现的前列腺癌，大多已经是转移或扩散之后了。

We are catching more and more of these cancers only after they have already metastasized or spread.

这就是我们说的四期癌症。

That's what we call stage four disease.

一旦到了四期，情况就完全不一样了。

Once you're at stage four, the picture changes dramatically.

五年生存率跌到38%，从确诊到去世的中位时间大概只有两年半。

Five year survival falls to thirty eight percent, and the median time from diagnosis to death is about two and a half years.

所以，我觉得这个问题必须得有个答案：

So, the question that I think demands an answer is quite straightforward.

我们怎么会走到这一步？

How did we get here?

筛查工具我们明明都有啊。

We have the screening tools.

早期前列腺癌我们是有有效疗法的。

We have effective therapies for early cancers.

那为什么治疗效果反而越来越差，而不是更好呢？

Why are outcomes getting worse instead of better?

最关键的是，我们到底该怎么做才能改变现状？

And of course, most critically then, what do we need to do about this?

要回答这些问题，得先从PSA到底是什么说起，因为这是整个讨论的核心。

Now, to answer any of that, you need to start with the basics of what the PSA actually is, because it's the linchpin of this entire conversation.

说实话，要是其他每种癌症都有像PSA这样的标志物，今天癌症的死亡率根本不会是现在这样。

Quite frankly, if we had the PSA equivalent for every other cancer, the world could look a heck of a lot different than it does today with respect to cancer mortality.

PSA，也就是前列腺特异性抗原，从90年代初就开始用血液检测了。

PSA, which stands for prostate specific antigen, has been available as a blood test since the early 90s.

它是由前列腺分泌的一种蛋白质。

It's a protein made by the prostate gland.

它的生理作用是让精液保持液态。

Its biological function is to help keep seminal fluid in a liquid state.

前列腺会自然释放一点点PSA进入血液，我们抽血检测的就是这个量。

A tiny amount of PSA naturally leaks from the prostate into the bloodstream, and that's what we measure when we draw a person's blood.

这里有个关键的生理学要点。

Here's the kind of important physiologic point.

随着年龄增长，几乎每个男性的前列腺都会增大，血液里的PSA水平也会随之上升。

As the prostate grows, which happens in virtually all men as they age, the amount of PSA in the blood tends to rise proportionally.

PSA检测刚推出时，逻辑很简单：

When the PSA test was first deployed, the logic was simple.

如果你的PSA值异常偏高，说明前列腺体积异常大，这可能是个危险信号。

If your PSA is unusually high, your prostate is unusually large, and that could mean trouble.

PSA偏高就会做超声，超声异常就安排活检，活检发现癌症就立刻治疗。

An elevated PSA would prompt an ultrasound, an abnormal ultrasound would trigger a biopsy, and cancer on a biopsy would lead to treatment.

早期的数据看起来还挺靠谱的。

The early data on this approach were generally reasonable.

两项大规模研究，分别追踪了14年和16年，结果显示，常规PSA筛查让前列腺癌死亡率分别下降了44%和64%。

Two large trials, followed over fourteen and sixteen years respectively, showed that routine PSA screening cut prostate cancer mortality by forty four and sixty four percent, respectively.

这意味着，每一千名接受筛查的男性中，就能避免多达3.1例转移性——也就是致命的——前列腺癌。

That translates to preventing up to three point one cases of metastatic, which means fatal, disease for every one thousand men who went through the screening process.

检测本身几乎不花钱，就是一次常规抽血，大部分保险都全额报销。

The test itself costs nothing, a standard blood draw, fully covered by most insurance plans.

所以你自然会问：那为啥不给所有人都做筛查呢？

So, you would naturally ask, why wouldn't we screen everyone?

但接下来事情就变了味儿，我觉得后果特别严重。

Well, here's where the story takes a turn that I think had a devastating set of consequences.

尽管当时做决策的人，至少在逻辑上是讲得通的。

Even though the people who made the decision were operating at least somewhat with reasonable logic at the time.

问题在于，从PSA升高直接推到做活检，这流程产生了太多假警报。

The problem was that the straight line from elevated PSA to biopsy was generating too many false alarms.

PSA升高原因很多，跟癌症一点关系都没有，比如良性增生、暂时性发炎——像前列腺炎发作时那样，最近有过性生活，甚至单纯就是个体差异。

PSA can be elevated for many reasons that have nothing to do with cancer, including benign enlargement, transient inflammation, such as you might experience during a bout of prostatitis, recent sexual activity, and frankly even just natural variation.

但那些因为PSA偏高而做的活检，可一点都不轻松。

But the biopsies that followed an elevated reading were hardly benign.

标准做法是用针从直肠壁穿进去取前列腺组织样本。

The standard approach involved punching a needle through the rectal wall to sample prostatic tissue.

这就等于在细菌密集的区域和本该无菌的器官之间，硬生生打通了一条污染通道。

Now you're creating a contaminated pathway from a bacteria rich environment into what should be a sterile organ.

就算用了预防性抗生素和术前准备，这些活检的感染率还是高达百分之五到七，一想到做这种检查的人数那么多，总的并发症数量就吓人了。

Even with things like prophylactic antibiotics and preparation, infection rates from these biopsies ran between five and seven percent, which of course, when you multiply that across the number of people that were having them, is an enormous amount of morbidity.

前列腺感染可不是小事，尤其是要是细菌进了血流，那就更危险了。

Prostate infections, of course, are not a joke, especially if they reach into the bloodstream.

很多人因此被送进急诊室。

They would frequently land men in the emergency room.

不少人得住院，还得请假停工。

They could lead hospitalizations and take people away from work.

除此之外，还有过度治疗的问题。

So, on top of that, there was the overtreatment issue.

在九十年代和两千年初，只要活检发现癌细胞，几乎都会立刻开始治疗。而手术治疗的代价可不小——勃起功能障碍、尿失禁、肠道问题，要是用放疗，这些问题更明显。

So, back in the 90s and early 2000s, finding cancer on a biopsy almost invariably led to treatment, And that treatment, surgical, carried real consequences, erectile dysfunction, urinary incontinence, bowel problems, especially if radiation was used.

单是癌症诊断本身带来的心理压力就非常大。

The psychological weight of a cancer diagnosis alone is enormous.

从那以后我们逐渐明白，早期PSA筛查发现的很多癌症其实长得特别慢。

What we've come to understand since then is that a significant fraction of the cancers caught during the early PSA era were actually quite indolent.

这些癌症根本不会发展到威胁生命的地步。

They were never going to progress to the point of threatening someone's life.

这些男人却要承受全套癌症治疗的负担，而如果放着不管，这病根本不会伤他们分毫。

These men were being subjected to the full burden of cancer treatment for a disease that, if left alone, would never have harmed them.

泌尿科有句老话：每个男人都会得前列腺癌，但只有少数人会因此丧命。

There's a saying in the urology world that says, Every man will get prostate cancer, but some will die of it.

意思是，只要你活得够久，几乎都会在前列腺细胞里发现癌变。

The idea here is if you live long enough, you're always going to find prostate cancer inside some cells of the prostate.

关键不在于有没有癌细胞。

That's not the jugular question.

真正要紧的问题是：这些癌变里，有多少会从前列腺扩散到别的器官，尤其是骨头——这是最常见的转移部位。

The jugular question when you identify prostate cancer is how many of these cases are cases where, if left untreated, the cancer will spread from this organ to a distant organ, namely the bone, which is the most common place of spread.

所以，针对这些情况，美国预防服务工作组采取了行动。

So, in response to all of this, the United States Preventative Service Task Force, or USPSTF, made its move.

2008年，他们不再建议70岁以上的男性做PSA筛查。

And in 2008, they stopped recommending PSA screening for men 70.

到2012年，他们把不推荐筛查的建议扩展到了所有年龄段的男性。

By 2012, they extended that recommendation against screening to men of all ages.

他们最依赖的数据来自一项大型美国研究，叫前列腺癌、肺癌、结直肠癌和卵巢癌筛查试验，简称PLCO。

The data they leaned most heavily on came from a large American trial called the Prostate Lung Colorectal and Ovarian Cancer Screening Trial, or PLCO.

这项研究的前列腺部分把男性随机分成两组，一组做PSA筛查，另一组不做，结果发现两组的前列腺癌死亡率几乎没有差别。

The prostate arm of this study randomized men to either undergo PSA screening or not, and it found essentially no difference in prostate cancer mortality between the two groups.

这意味着，筛查最多只能让每一千名受检男性中多活1.3个人。

The implication was that screening saved, at best, one point three lives per thousand men tested.

所以，预防服务工作组的算盘大概是这样：

So, the USPSTF's calculus went something like this.

你为了救不到千分之一的男性，却让那么多人承受严重的副作用——就是我们之前说的那些问题，对吧？

If you're only saving one tenth of one percent of men while causing serious complications, all the things we talked about, right?

感染、尿失禁、勃起功能障碍，还有这些带来的心理压力，对相当一部分人来说，代价远大于收益。

Infections, incontinence, erectile dysfunction, the stress that's associated with all of these things, in a meaningful proportion of the others, the math simply doesn't add up.

过度诊断和过度治疗带来的伤害，已经超过了它的好处。

The harms of overdiagnosis and overtreatment exceed the benefits.

我能理解为什么有人会得出这样的结论。

Now again, I can see how one could arrive at that conclusion.

这有点像功利主义的思路，在群体层面上确实有它的道理。

It's a little bit of a utilitarian argument, and there's a logic to it at the population level.

但这个逻辑成立的前提是，底层数据得靠谱，这个我们待会儿再聊。

That logic only holds if the underlying data are sound, which we'll discuss.

现在已经过去十五年了。

And it's been fifteen years now.

如果美国预防服务工作组当初的判断是对的，那晚期前列腺癌的发病率应该只会有极微小的上升，可能就零点几个百分点。

If the USPSTF got it right, we should see at most a marginal uptick in late stage disease, maybe a fraction of a percent.

接下来很自然的问题就是：过去这十五年，实际发生了什么？

The obvious next question is, what has actually happened over the past fifteen years?

现在数据已经出来了，情况非常明确，也让人非常担忧。

Well, the data are now in, and they paint a very clear and very troubling picture.

把所有分期为一到三期的前列腺癌合并来看——也就是还没转移的——五年存活率超过百分之九十九。

When you group together all prostate cancers caught at stages one through three, so these are non metastatic, five year survival exceeds ninety nine percent.

但到了四期，也就是癌细胞已经扩散出前列腺的时候，存活率骤降到百分之三十八，确诊后中位生存期大约只有三十个月。

But at stage four, which is metastatic disease, tumors that have spread beyond the prostate, survival plummets to thirty eight percent, with a median survival of about thirty months from diagnosis.

所以，发现癌症的时间点，绝不是个小细节。

So, the timing of when you find the cancer is not a minor detail.

这简直就是决定生死的关键因素。

It's arguably the determining factor in life and death.

那最近的研究数据到底显示了什么？

So, what does the recent literature show?

过去六个月里，美国和加拿大两个登记系统发布的数据表明，我们发现的前列腺癌，越来越多是在已经转移之后才被诊断出来的。这建立在泰德·谢弗及其团队2016年的研究基础上。

Well, data published within the last six months from both the American and Canadian registries, which builds on the earlier work from Ted Schafer and his colleagues in 2016, is that we are finding more and more prostate cancers only after they've become metastatic.

这正是当年很多泌尿科医生预测会发生的情况——当我们减少筛查后。

This is exactly what many urologists predicted would happen when we pulled back on screening.

但更令人担忧的是，受影响的不只是老年男性。

But what's even more alarming is that it's not just older men who are affected.

加拿大数据显示，2010到2017年间，75岁男性中四期前列腺癌的诊断率每年上升3.7%。

The Canadian data show a three point seven year over year increase in stage four diagnoses among men 75 between twenty ten and twenty seventeen.

尽管同一年龄段发现的癌症总数其实是在下降的。

This is happening despite a declining total number of cancers detected in that same age group.

所以，并不是得癌的人变多了。

So, it's not that more men are getting cancer.

而是我们总等到癌细胞扩散了才查出来，这时候已经没法根治了。

It's that we're only finding it once it's too late to cure.

美国的数据也讲了同样的故事。

The American data tell a similar story.

自从2012年指南调整后，全年龄段的二期癌症检出率每年下降约0.1%。

Since the 2012 guideline shift, stage two cancer detection has been declining by about zero point one percent per year across all ages.

与此同时，三期癌症每年上升3.3%，四期更是每年飙升6%。

Meanwhile, stage three has been climbing at three point three percent per year and stage four at six percent per year.

晚期癌症的检出率增长，远远超过了总病例每年仅零点八个百分点的缓慢上升。

Those increases in late stage detection far outpace the modest zero point eight percent annual increase in total cases.

所以，这里的解读其实很简单，一点也不模糊。

So, the interpretation here is not complicated and it is not ambiguous.

我们不再主动筛查早期病变，自然就只能等到病情晚期才发现了。

We stopped looking for early disease, so we started finding it late.

四期前列腺癌才是导致几乎所有前列腺癌死亡的主因。

Stage IV cancer is what drives all prostate cancer mortality, or nearly all of it.

我们现在的状况，完全是当初那条指南带来的必然结果——它告诉医生和患者：查了也没啥用，不值得折腾。

The trajectory we're on is the entirely predictable result of a policy that told doctors and patients that looking wasn't worth the trouble.

我觉得加拿大研究者对这个悖论总结得特别到位，我 paraphrase 一下：虽然新疗法延长了转移性患者的生存期，但整体人群的生存率反而比推荐筛查时更差了，因为我们现在有太多人一确诊就是无法治愈的晚期癌。

I think the Canadian researchers summarized this paradox well, and I'm paraphrasing, but the gist was newer treatments have extended survival for men with metastatic disease, but overall survival across the population has actually worsened compared to when screening was recommended, because we now have so many more men presenting with incurable cancer.

这根本不是注定要走的路。

It doesn't have to be the story.

事情本不该是这样的。

It just shouldn't be this way.

现在我想换个话题，因为我觉得这才是整个对话里最重要、也最让人充满希望的部分。

This is where I want to pivot, because I think this is actually the most important part of the conversation, and honestly, most hopeful.

美国预防服务工作组当年制定指南时，我们的检测手段远没有今天这么先进。

The USPSTF built its guidance at a time when our tools were far cruder than they are today.

就像我几分钟前提到的，过去的流程基本上是：PSA一升高，就做超声；超声要是有点可疑，就直接穿刺活检。

The old pipeline, as I kind of talked about a few minutes ago, was essentially PSA goes up, you get an ultrasound, ultrasound looks somewhat concerning, you get a biopsy.

只要活检发现一点癌细胞，立马就开始治疗。

If the biopsy finds any type of cancer, you get treated.

那个流程里头几乎没有弹性可言。

There was very little nuance in that algorithm.

但到了2026年，或者说过去五年里，我们用PSA的方式已经完全不一样了。

But the way we deploy PSA in 2026, and quite frankly over the last five years, looks poignantly different.

最大的观念转变就在这儿：PSA的价值不在于一次性的数值，而在于它长期的变化趋势。

The single biggest conceptual shift is this: PSA is most valued as a longitudinal trend, not a single snapshot.

单次的PSA读数本身其实很不稳定。

Any individual PSA reading is inherently noisy.

每天的数值波动可能高达15%。

Day to day values can fluctuate by as much as 15%.

男人刚有过性生活，PSA值就可能飙升40%，而且人与人之间的差异大得惊人。

If a man has recently ejaculated, his PSA can spike by as much as 40%, and the person to person variability is staggering.

一个六十多岁的健康男性，PSA中位数大概在1.0到1.2之间，但同年龄段、没有前列腺癌的男性，第95百分位数居然能高达4.9。

A healthy man in his sixties might have a median PSA of one point zero to 1.2, but the ninety fifth percentile for that exact same demographic in men with no prostate cancer extends all the way up to 4.9.

我们在节目笔记里会放一张表，把所有这些数据都列清楚。

So, in the show notes, we're going to leave a table that gives you all of this information.

我们会按每十年一个阶段来细分，但关键在于，单看一个PSA数值，其实没啥意义。

We break it down by a decade of life, but the point here is that no single PSA value in isolation tells you very much.

真正能说明问题的是变化趋势，这就是我们说的PSA增速——追踪患者基线值随时间的变化速率。

What does tell you something is the trajectory, and this is what we call PSA velocity, mapping a patient's baseline over time and tracking the rate of change of that PSA value.

前列腺本来就会随着年龄增长慢慢变大，所以PSA缓慢上升是正常的，但要是涨得太快，就得警惕了。

The prostate naturally enlarges with age, so some gradual PSA increase is expected, but rapid increases are cause for suspecting something pathological.

要么是前列腺异常增生，要么是PSA从前列腺组织漏进血液的比例变高了，也可能两个情况同时存在。

Either the prostate is enlarging abnormally, a higher proportion of PSA is leaking into the blood relative to the amount of prostate tissue, or both.

前列腺结构紊乱和血管渗漏，是恶性肿瘤的典型特征。

Disrupted prostate architecture and vascular leakage are the hallmarks of malignant growth.

所以一般来说，如果我们观察持续十八个月的上升趋势，并根据基线值设定不同的阈值……

So in general, if we look at increases sustained over an eighteen month window and use different cutoffs depending on the baseline value.

比如，如果一个病人的基线PSA低于每毫升4纳克——在我们这儿，这很常见。

So if we took a patient with a baseline PSA of less than four nanograms per milliliter, and in our practice, that's the norm.

我们大多数男性的基线PSA都低于4。

Most of our men are going to walk around with a baseline PSA less than four.

如果连续十八个月，每年上升超过0.35纳克/毫升，我们就得警惕了。

A sustained rise by more than about 0.35 nanogram per milliliter per year over eighteen months is generally our red flag.

如果病人的PSA一开始就在4以上，那我们允许它每年涨到0.75纳克/毫升左右才考虑干预。

In patients with a PSA value that starts above four, we would let that increase to about a 0.75 nanogram per milliliter per year bump before we would flag that.

咱们来点实际的例子。

So let's make this tangible.

比如说，我有个55岁的病人，PSA是1.3。

So let's say I have a 55 year old patient with a PSA of 1.3.

这比他这个年龄的中位数略高一点，但我并不担心，尤其是因为我有他的长期数据，知道他平时就稳定在这个水平。

So that's slightly above the median for his age, but I'm not alarmed, especially because remember, I've got longitudinal data on him and I realized that this is about where he settles out.

他有一次到过1.6，但我没慌，因为两三个月后他又回落到1.3了。

That one time he was 1.6, I didn't overreact because two months later or three months later, he was back to 1.3.

但如果一年后他再来，PSA升到1.7，再过六个月又升到1.9，那就是十八个月内涨了0.6，折合每年0.4的增速。

Now, if he comes back a year later at 1.7, and then six months after that comes back at 1.9, that's an increase of 0.6 over an eighteen month period of time, working out to a velocity of 0.4 per year.

这时候我就得留心了。

So now I'm paying attention.

这种持续的上升趋势才是我要找的信号，而且是专门针对他个人的。

That sustained acceleration is the signal I'm looking for, and it's personalized to him.

这其实就是精准医疗的真谛，神奇的是，它几乎不花什么钱——这检测便宜得离谱，就几美元，还藏在常规抽血里。

This is actually what precision medicine is, and incredibly, it costs essentially nothing because this test is so cheap, like we're talking dollars, and it shows up in a routine blood test.

这真是精准医疗的绝佳例子，而且几乎不用额外花钱，只要做一次常规抽血就行。

So, this is a great example of precision medicine, and incredibly, it costs essentially nothing beyond showing up for a routine blood draw.

再说一遍，抽血本身也就几美元的事。

Again, the blood test itself costs dollars.

但即使他的增速引起了关注，我们也不会再直接建议做活检了。

But even with his velocity flagging a concern, we no longer would just jump to a biopsy here.

下一步应该是做核磁共振，它的分辨率高得多，而且比直接做活检要微创得多。

The next step would now be an MRI, which serves as a much higher resolution test and it's much less invasive than proceeding to a biopsy.

所以，核磁共振还能给我们另一个指标——PSA密度，就是血液里的PSA浓度除以影像测出的前列腺体积。

So, the MRI gives us yet another metric, which is PSA density, which is simply the PSA concentration in the blood divided by the volume of the prostate provided by imaging.

其实用超声波也能算这个值。

By the way, you could do that with an ultrasound as well.

但用核磁共振的话，等于一次检查拿到两个信息：不仅图像更清晰，还能直接测出体积。

But with the MRI, you're getting two for one because you're getting a better imaging study and of course you're getting volume.

道理是这样的。

Here's the logic.

健康的前列腺会自然增长，PSA和体积通常是同步上升的。

A healthy prostate grows, PSA and volume tend to increase in approximate proportionality.

但一旦出现恶性肿瘤，它会破坏前列腺原本的结构，让PSA不再被正常限制在腺体里，或者影响穿过前列腺的血管内皮。

But when you have a malignancy, the tumor can disrupt the normal architecture of the prostate that normally contains PSA to the gland or alter the endothelia running through the prostate.

在这种情况下，PSA会以远超前列腺大小所应产生的速度泄漏到血液里。

In this situation, PSA starts escaping into the bloodstream at a rate that outpaces what you'd expect from the size of the gland alone.

如果PSA的上升速度明显快于前列腺体积的增长，这就强烈暗示有问题了，而且在任何人考虑穿刺之前，我们就能提前捕捉到这个信号。

If PSA is rising disproportionately to prostate volume, that's a strong indicator that something is wrong, and it gives us that signal before anybody needs to think about a needle.

把连续血液检测中的PSA增速和MRI测出的PSA密度结合起来，如今PSA筛查的分辨能力，早就比美国预防服务工作组当年做判断时强多了。

When you put your PSA velocity from serial blood tests together with PSA density from MRI, the discriminating power of PSA screening today is dramatically better than what existed when the US PSTF made its call.

现在，如果我们稍微聚焦一下MRI，最近有个重大进展，我觉得会彻底改变它的可及性。

Now, if we focus in on MRI for a moment, there's been a really significant development that I think is going to meaningfully change the accessibility equation.

除了PSA密度，MRI在这个流程里的主要价值在于，它能直接在前列腺里发现可疑的病灶或异常区域，而不用做侵入性操作。

Beyond PSA density, the main value of MRI in this algorithm is that it can identify suspicious lesions or regions in the prostate without invasive probing.

它能可靠地判断是否需要穿刺，如果确实需要，还能精准引导针头扎到最可能确诊的部位。

It can credibly rule in or rule out the need for a biopsy, and if a biopsy is warranted, it guides the needle to the areas most likely to hand us a diagnosis.

过去最大的障碍是，金标准的多参数MRI必须使用一种叫钆的造影剂。

The obstacle historically was that the gold standard prostate MRI called a multi parametric MRI requires a contrast called gadolinium.

这就意味着成本更高、需要医护人员打静脉针，而且扫描时间也长得多。

And that meant higher costs, the need for a medical professional to administer an IV injection, and significantly more time in the scanner.

这些因素自然限制了患者的接诊量，让活检前的MRI在很多情况下根本没法落地。

All of this of course limited patient throughput and made pre biopsy MRI impractical in many scenarios.

但2025年开展的PRIME研究彻底改变了这一局面。

But a trial in 2025 called the PRIME trial changed this.

这项研究直接对比了完整的多参数方案——包括T2加权成像、弥散加权成像和动态增强扫描——和一个去掉造影剂的简化双参数版本。

The study directly compared the full multi parametric protocol, which is a T2 weighted image, a diffusion weighted image, plus dynamic contrast enhanced imaging against a stripped down contrast free bi parametric version that drops the contrast component altogether.

目标就是验证简化版是否不劣于金标准。

The goal was to establish non inferiority.

换句话说，研究想弄清楚：这个简化版能不能跟金标准打得平手？

In other words, the question asked was, does this stripped down version perform at least as well as the gold standard?

结果呢，两者的表现几乎不分胜负。

The results were essentially a dead heat.

双参数MRI在490名PSA筛查异常的患者中，成功发现了143例有临床意义的癌症。

The bi parametric MRI identified clinically significant cancer in one hundred and forty three out of four ninety men who had been flagged by PSA screening.

而用了钆造影剂的完整多参数MRI，在同一组490名患者中，发现了145例。

Whereas the full multi parametric MRI complete with gadolinium caught one hundred and forty five out of that same group of four ninety study participants.

这两组检出率只差了0.4个百分点，统计上根本看不出区别。

The difference between those detection rates was zero point four percentage points, which was statistically indistinguishable.

这实际意义可太大了，明摆着的吧？

The practical implications here are huge, obviously, right?

不用造影的话，扫描时间直接减半，十五到二十分钟就能搞定，不用再等三十到四十分钟。

Without contrast, the scan takes half the time, fifteen to twenty minutes instead of thirty to forty.

不用专门有人在旁边给你打造影剂、盯着你操作。

You don't need a medical practitioner that's standing there giving you the contrast and overseeing you.

成本降了，速度提了，好处一箩筐。

Of course, the costs come down, speed goes up, etcetera.

不过话说回来，就算无创筛查进步这么大，还是有一部分男人最终得做活检。

Now, with all of these improvements in non invasive screening, some men are still going to need a biopsy.

要是MRI发现了可疑迹象，你得靠组织样本才能确诊，那唯一的选择就是活检。

If the MRI flags something suspicious and you need tissue to know what you're dealing with, you've only got one place to get it.

这方面其实也有很大进展，值得说一说，因为活检本身现在又更安全、又更准了。

It's worth talking about the progress that's been made there as well, because the biopsy itself has gotten both safer and more accurate.

前面提到过，传统做法是经直肠取样，但这样很容易把直肠里的细菌带到本该无菌的区域，风险本来就挺大的。

Now, mentioned earlier that the traditional approach was a transrectal approach, and that carries inherent risk of poking bacteria from the rectum into a sterile space.

而且这种做法在解剖上也有局限。

It also has its anatomical limitations.

它取样的部位容易偏向前列腺后部，靠近直肠壁，结果就可能漏掉前列腺的前部和底部。

It biases your sampling towards the back of the prostate, near the rectal wall, and this can miss the front and base of the gland.

另一种方法叫经会阴穿刺，就是从肛门和阴囊之间的皮肤进针。

The alternative to this is called a transperineal approach, entering through the skin between the anus and the scrotum.

这样完全绕开了直肠，感染风险大大降低，还能更全面地覆盖前列腺的前部和尖部——而这些地方，经直肠取样经常够不着。

This completely bypasses the rectum, which dramatically reduces infection risk, and it opens up much better access to the anterior and apical portions of the prostate than the transrectal route does, which it tend to miss.

泰德·谢弗，这位老朋友多次上过我们的播客，也是我私人关系特别好的医生，专门负责我们很多前列腺癌患者的诊疗。他参与了一项大型多中心三期临床试验，入组了1700多名患者，直接对比了这两种取样方式在癌症检出率和并发症上的差别。

Ted Schaefer, who's been a guest on this podcast many times, is a very close friend of mine personally, and is also the urologist that works with many of our patients when they are diagnosed with prostate cancer, was involved in a large multi center phase three trial with over 1,700 patients that compared cancer detection rates and complication profiles between the two approaches head to head.

经会阴取样检出的高级别癌症更多，低级别癌症更少，说明它更能抓到真正有威胁的肿瘤，减少了对惰性病灶的误判，自然也减轻了患者的心理负担。

The transperineal biopsy detected more high grade cancers and fewer low grade ones, which tells you it's doing a better job of finding tumors that actually matter, generating fewer false negatives from indolent disease and obviously creating less emotional distress.

说到安全性，这可能是最亮眼的成果——在这项研究里，接受经会阴穿刺的患者，一个都没感染。

And on the safety front, this is really the headline in my mind, not a single patient who underwent the transperineal biopsy in that study developed an infection.

零感染。

Zip zero.

再对比一下经直肠活检高达5%到7%的感染率。

Compare that to the five-seven percent infection rate widely reported in the transrectal approach.

更重要的是，经会阴活检不需要预防性使用抗生素，这对患者和整个抗生素合理使用都是个大好处，毕竟我们现在正面临抗生素耐药的挑战。

Importantly, the transperineal method doesn't require prophylactic antibiotics, which is a meaningful benefit both for the patient and for the antibiotic stewardship more broadly as we face an era of antibiotic resistance.

不过，目前还没普及。

Now, adoption isn't universal yet.

在美国，只有大约37%的泌尿科医生做经会阴活检，而几乎所有人都在做或能做经直肠活检。

Only about thirty seven percent of American urologists currently perform transperineal biopsies versus essentially all of them doing transrectal or being able to.

所以，证据和实际做法之间还有差距，但趋势是向好的。

So, there's a gap between what the evidence supports and what's happening in practice, but the trajectory is encouraging.

好了。

All right.

我一直在讲要多筛查、多做核磁、用更好的活检，但我没忘记当初反对意见的另一面——过度治疗的问题。

So, I've been building the case for more screening, for more MRI, and for better biopsies, but I haven't forgotten the other side of the original argument, which is the overtreatment problem.

我真的很重视这个问题，因为现在外科技术虽然进步了，但前列腺手术绝不是什么小手术。

I really take this seriously because with all of the advances in surgical care, this is not a benign operation.

不是所有的前列腺癌都会要命。

Not every prostate cancer is going to kill you.

我们的治疗确实有效，但副作用谁都不想碰，除非真的别无选择。

Our treatments are effective, but they carry side effects that nobody wants to experience if they don't have to.

关键在于，我们现在不再一发现癌症就立刻开刀了。

Here's the critical point that I think changes the overtreatment We no longer treat every cancer we find.

现在的决策流程已经精细多了。

The decision tree has gotten much more sophisticated.

如果你还记得我们以前聊过这个话题的播客，我们讲过一种叫‘格里森评分’的东西。

Now, if you remember the podcast that we've covered in this topic in the past, we go through something called a Gleason scoring.

不过我还是简单再讲一遍，怕不是每个人都记得之前的内容。

But I'm just going to kind of reiterate it here a little bit because maybe not everybody's familiar with that previous content.

当病理医生检查活检样本时，会在显微镜下观察细胞，判断它们和正常细胞相比有多异常。

So, when a pathologist examines a biopsy specimen, they look at the cells under the microscope and they decide how abnormal the cells look relative to healthy cells.

他们用一个叫格里森评分的分级系统。

They use a grading scale called a Gleason score.

这个评分有两个数字，因为他们检查了两个不同的区域。

Now, you're getting two numbers in that score because they're looking in two places.

你可能会得到3+3、3+4，或者4+4这样的分数。

You might get a Gleason three plus three, or three plus four, or four plus four.

最高分是5分，分数越高，细胞的恶性程度就越高。

The highest number there is five, and the higher the number, the greater the malignant potential of the cell.

这些分数会被合并成一个分级组，范围从1到5。

Now, these numbers get compressed into a grade group, which is a scale that is graded one through five.

同样，这也是根据细胞的异常程度来划分的。

Again, it's similarly based on the abnormality of these cells.

所以，1级或2级的肿瘤风险相对较低。

So, a grade one or two is a relatively low risk tumor.

我们很清楚，1级和2级——也就是低格里森评分的肿瘤——其发展轨迹完全不同。

We know the natural history of grade one and grade two, which are the lower Gleason scores, behave very differently.

这些癌症可能根本不会转移。

These are cancers that may never spread.

虽然我们不能百分百确定，但我们知道，如果真要转移，它们一定是先升级到更高的戈森评分等级。

Now, we don't know that for a fact, but we know that if they're going to spread, they're going to do so by progressing into a higher grade Gleason score.

所以对这类患者，我们可以继续密切观察，或者采用更先进的监测手段——稍后我会详细讲。

Therefore, for these patients, we can continue to surveil them or do other advanced forms of monitoring, which I'll talk about in a second.

相反，如果患者是高级别，比如三级，对应戈森评分4+3；四级是4+4；五级就更高了，比如4+5、5+4，或者任何5+5的情况。

Conversely, if a patient presents with a higher grade group, like a grade three, which would be a Gleason four plus three, a grade four, which would be a Gleason four plus four, or a grade five, which is anything higher, so a four plus five, five plus four, or any five point five.

这些肿瘤非常凶险，必须马上治疗。

These are very aggressive tumors and treatment is immediately warranted.

再回过头说说一级和二级该怎么办？

Going back to what do you do with grade one and two?

这些患者确实得了前列腺癌，但我们认为它短期内并不会危及生命，因为还不确定这些癌会不会转移；就算会，也得先慢慢恶化才行。

Well, again, these are patients that have prostate cancer, but our belief is that it is not an imminent threat to their life because it is not clear if these cancers will spread, and if they're going to turn into spreading cancers, they're going to do so by progressing.

所以这种情况下，我们会看其他血液指标，比如PHI或者4Kscore这些检测。

So, we would in this case look at other blood markers like tests called the PHI or the four ks score.

这些内容我们在之前的播客里都聊过。

These are things that we talked about on previous podcasts.

如果你想知道更多细节，我们会在节目笔记里附上相关链接。

We'll link to some of that stuff in the show notes if you want to follow that in more detail.

但重点是，我们现在要进入一个叫‘主动监测’的领域。

But the point is we now turn into an area called active surveillance.

主动监测就是确保一旦需要治疗，我们能及时介入，但绝不会过早下手。

Active surveillance is basically something we're doing to ensure that treatment will be timely once it is required, but no sooner.

十五年前那种一发现癌症就立刻治疗、不管后果如何的做法，现在基本已经被泌尿科医生淘汰了。

The scenario that drove so much of the overtreatment concern fifteen years ago, which was you find any cancer, you treat it immediately, and you deal with the consequences, that's largely been retired from the urologist playbook.

如今，泌尿科医生有了更先进的工具和临床判断能力，能真正区分哪些肿瘤危险、哪些可以安全地观察，这才让我们有了这种底气。

The tools and clinical judgments that have evolved today to the point where urologists can meaningfully distinguish between dangerous tumors and ones that can be safely watched is what basically gives us this luxury.

这意味着，筛查的利弊权衡已经大幅向支持筛查的方向倾斜。

That means that the risk benefit calculation for screening has shifted substantially in favor of screening.

明白了。

Okay.

所以我花了不少时间梳理了现代筛查工具包。

So I spent a good amount of time walking through the modern sort of screening toolkit.

一路上，我也尽量公平地还原了美国预防服务工作组最初的逻辑。

I've tried to be fair to the original USPSTF reasoning along the way.

我觉得过度治疗的担忧确实有道理，经直肠活检带来的负担也是实实在在的。

I think the overtreatment concern was legitimate, and I think the burden of trans rectal biopsies was real.

这些反对意见，我都很认真地看待。

Again, I take those objections seriously.

但有一件事，我直到现在才打算说出来。

But there's something I've sort of held back on until now.

那就是数据上一个重大漏洞，它严重到足以动摇美国预防服务工作组立场的根基。

And it's a failure in the data that I think is so significant that it essentially undermines the entire foundation of the USPSTF position.

泌尿科医生们早就指出过这个问题了，我觉得他们居然没推动指南正式修订，简直难以置信。

Urologists have been pointing this out for years, I think it's borderline unbelievable that it hasn't led to a formal revision of the guidelines.

我说的就是那个PLCO试验。

So, I'm talking about that PLCO trial.

就是这项研究，让USPSTF觉得PSA筛查根本不值得做，所以他们特别倚重这个结果。

That's the study that the USPSTF weighted most heavily when it decided that PSA screening wasn't worth doing.

PLCO研究本来打算证明的是这个：

Here's what the PLCO study was supposed to show.

找一大群男性，随机分成两组，一组定期做PSA筛查，另一组不做。

You take a large group of men, you randomize half to get regular PSA tests, the other half not to get tested.

然后跟踪他们十年，对比两组前列腺癌的死亡率。

You follow them over a decade and compare prostate cancer deaths between the two groups.

结果发现，两组死亡率几乎没差别，于是得出结论：筛查对降低死亡率没啥用。

The study found essentially no difference, supporting the conclusion that screening doesn't meaningfully reduce mortality.

但问题出在哪儿呢？我第一次听说的时候，简直不敢相信。

But here's what went wrong, and I genuinely had trouble believing this the first time I encountered it.

对照组——就是那些不该做筛查的人——其实私下都在做筛查。

The control arm, so this is the group that was not supposed to be screened, was getting screened anyway.

研究人员没主动提供检测，但问过参与者后发现，没筛查组里有40%到60%的人，过去一年里都做过PSA检查。

The investigators may not have been providing the tests, but when they surveyed the participants, somewhere between forty and sixty percent of men in the no screening group reported having had a PSA test within the year.

这可不是一次性的污染问题。

This wasn't a one time contamination event.

整个研究期间，每年都是一样。

That pattern held every single year of the study.

到最后一次调查时，对照组里超过九成的男性都至少做过一次PSA检测。

By the final survey, over ninety percent of the men in the control arm had undergone at least one PSA test.

有些年份， supposedly 不做筛查的那组报告做筛查的人，反而比真正做筛查的组还多。

In some years, more men in the supposed control arm reported screening than in the intervention arm.

我们会在节目笔记里放上2016年发表在《新英格兰医学杂志》那封读者来信里的数据，你自己看看，真的挺惊人的。

We will put the figure from the 2016 letter to the editor in the New England Journal of Medicine in the show notes so you can see this for yourself, because it is quite striking.

说白了，这研究根本就是在拿PSA筛查跟PSA筛查做对比，然后发现没差别，就下结论说筛查没用。

The bottom line is, this was a study comparing PSA screening to PSA screening, and then concluding that screening doesn't work when they didn't find a difference.

就是靠这个基础，USPSTF才推出了一个影响了上千万男性的建议。

That is the bedrock upon which the USPSTF built a recommendation that has affected tens of millions of men.

不过，这个数据污染的问题，一直到2016年才被广泛披露，早就过了原指南修改的时间了。

Now, this data contamination wasn't published widely until 2016, well after the original guideline change.

一旦这些数据公开，一群研究者在2017年重新回看PLCO的数据，做了一件特别聪明的事。

Once it was out there, a group of researchers went back to the PLCO data in 2017 and did something really clever.

他们用数学方法校正了对照组中筛查的频率，计算了平均筛查时间和早期发现的窗口期，也就是那些更常筛查的男性到底早多久被确诊，然后据此推算出因早期发现而减少的死亡率。

They mathematically accounted for the frequency of screening within the contaminated control arm, calculated mean and lead time, essentially how much earlier cancers were caught in men who were screened more regularly, and then imputed a mortality reduction based on earlier diagnoses.

当你用这种方式重新分析——也就是修正了原本让研究结果变得无法解读的污染数据后，同样的PLCO数据却显示：规律的PSA筛查能让前列腺癌死亡率降低27%到32%。

When you run the analysis that way, correcting for the contamination that made the original study essentially uninterpretable, the same PLCO data show a twenty seven to thirty two percent reduction in prostate cancer mortality attributable to regular PSA testing.

我真想让这句话好好沉淀一下。

I just want to sit with that for a second.

同样的数据集，同样的人群，只要诚实地分析，就能看出筛查能预防四分之一到三分之一的前列腺癌死亡。

The same data set, the same patients, analyzed honestly, and it shows that screening prevents roughly a quarter to a third of prostate cancer deaths.

可直到现在，USPSTF自2018年以来都没更新过指南。

And yet, the USPSTF has not updated its guidelines since 2018.

他们依然不建议55到69岁的男性做PSA筛查，对70岁以上的男性更是明确反对。

It still does not recommend PSA testing for men fifty five to sixty nine, and still recommends against it for men 70.

我觉得，USPSTF早就该重新审视这个建议了。

I think it's long past time for the USPSTF to revisit this.

加拿大预防保健工作组和美国家庭医师学会这些组织也是一样。

The same is true of organizations like the Canadian Task Force on Preventive Healthcare and the American Association of Family Physicians.

在他们改口之前，我觉得我们有充分理由自己做主。

Until they do so, I think we have reason to be confident in taking this into our own hands.

让我试着把我们刚才讲的内容总结一下，我知道信息量有点大。

Let me try to synthesize everything we've covered because I realize it's been a lot.

我们一开始注意到，减少PSA筛查后，无法治愈的前列腺癌发病率出现了实实在在的持续上升。

We started with the observation that pulling back on PSA screening led to a measurable ongoing increase in the incidence of incurable prostate cancers.

这可不是猜测。

That's not speculation.

数据清清楚楚摆在那里。

It's in the data.

多个国家的数据都是一致的，明明白白。

It's black and white from multiple countries.

接着我们梳理了PSA检测是如何演变的。

We then walk through how PSA testing has evolved.

每隔几年测一次PSA值，从来就不是个完美的筛查手段。

A single PSA value taken once every few years was never a perfect screening tool.

数据太杂了，个体差异也太大。

It's too noisy, too much individual variation.

以前的批评有一定道理，但现在有了PSA增速、PSA密度、多参数MRI和经会阴活检，再加上对低级别癌症的主动监测，这些方法综合起来，已经和USPSTF当年发布建议时的筛查模式完全不同了。

That part of the old critique was fair, but PSA velocity, PSA density, contrast free MRI, and transperineal biopsies, along with active surveillance for low grade disease, taken together, represent a fundamentally different screening paradigm than what existed when the USPSTF issued its recommendations.

我们现在能更早地发现那些致命的前列腺癌，

The ability to catch dangerous, I.

而且，

E.

还能大幅减少过度诊断和过度治疗的风险，进步可不是一点点。

Lethal cancers, early while avoiding the harms of overdiagnosis and overtreatment has improved by an order of magnitude.

然后我们回头看了十五年前推动放弃筛查的那些研究，发现核心论文根本站不住脚，数据被污染得厉害，根本没法用；而重新分析一遍，反而强烈支持继续筛查。

And then we looked at the data that supposedly justified the shift away from screening fifteen years ago and found that the cornerstone study was so contaminated as to be essentially meaningless, and that a proper analysis of the same data clearly supports screening very strongly.

那我们现在该咋办？

Where does that leave us?

前列腺癌，我说过，是男性第二大癌症杀手，但社会对它的重视远远不够。

Well, prostate cancer, as I said, number two cancer killer of men, and it's not receiving the urgency it deserves.

我还要再说得重一点。

I'll go further.

我们还在让男人死于这种本可以多年前就发现、本可避免致命的疾病，这简直不可接受。

I think it's unconscionable that we are still losing men to a disease that in many cases could have been caught years before it became lethal.

这一点我希望每个人都能真正记在心里，因为它关系到这种病本身的生物学特性。

This is something I want people to really internalize because it goes to the biology of the disease itself.

我以前在播客里提过很多次，但我觉得怎么强调都不为过。

I've talked about this many times on previous podcasts, but I don't think I can talk about it enough.

癌症大致可以分成两类。

Cancer falls into roughly two categories.

一类是进展相对可预测、有明确前期阶段、慢慢发展成致命威胁的。

There are those that progress in a relatively predictable, stepwise fashion, moving through detectable precursor stages before becoming truly dangerous.

还有一类则不是这样。

And then there are those that don't.

它们可能突然出现，迅速转移，不管筛查多频繁，都很难早期发现。

They can emerge suddenly, metastasize quickly, and evade early detection no matter how aggressively you screen.

我觉得胰腺癌就是典型的例子，可惜很多乳腺癌也属于这一类。

I think that pancreatic cancer is the classic example of the latter, and sadly, many breast cancers also fall into that category.

但前列腺癌和结直肠癌就完全不同，它们明显属于第一类。

But prostate cancer, along with colorectal cancer, fit squarely in the first group.

前列腺癌通常会沿着一条非常可预测的路径发展，从早期局限性病变慢慢进展到晚期转移性病变。

Prostate cancer tends to follow a very predictable path from early localized disease to advanced metastatic disease.

正是这种生物学特性，让PSA这样的筛查工具变得如此有效，也正因如此，每年仅在美国就有三万六千人死于前列腺癌——这样的死亡简直太令人痛心了。

That biological reality is precisely what makes a screening detectable tool like the PSA so powerful, and what makes any deaths, let alone the thirty six thousand a year in this country alone from prostate cancer, so completely tragic.

这并不是生物学的无情。

This isn't a cruelty of biology.

这是我们执行层面的失败。

It's a failure of our implementation.

我以前说过这个比喻，但我觉得值得再讲一遍。

I've made this comparison before, but I think it's worth repeating.

想象一下，如果我们有个乳腺癌检测工具，价格比一杯咖啡还便宜，能直接加进常规抽血检查里，还能在癌症扩散好几年前就发出预警——

Imagine we had a breast cancer detection tool that cost less than a cup of coffee, can be incorporated into a routine blood test, and was capable of flagging cancer years before it spread.

在哪个世界里，我们不会尽全力广泛推广这个工具？

In what universe would we not deploy that tool as widely and aggressively as humanly possible?

对于前列腺癌，这样的工具早就有了。

For prostate cancer, that tool does exist.

你的家庭医生在你下次抽血时加一项就行。

Your primary care doctor can add it to your next blood draw.

说不定你已经做过这项检查了。

It might already be there.

问题不在技术上。

The barrier isn't technology.

问题在于认知不足、教育缺失，最重要的是，指南太落后了。

It's awareness, it's education, and most of all, it's outdated guidelines.

在我们诊所，这种事我们见过太多次了。

In our practice, we've seen this play out countless times.

病人会带着其他医生做的PSA检测结果来找我们，有时候是好几年的数据，我们一算他们的增速，危险信号立马就出来了。

Patients will come to us with PSA data from other providers, sometimes years of it, and when we calculate their velocity, the red flags are right there.

我们会安排他们做核磁共振，根据结果决定是否做活检，结果发现好几例癌症都处在关键节点——要是再拖一年两年，很可能就转移了，但当时还是Gleason 3+4或4+3，正是治疗的最佳时机。

We send them for an MRI, depending on what it shows, a biopsy, and we've caught several cancers right at that stage where, had we waited another year or two, they likely would have been metastatic, but they were Gleason three plus 4s or four plus 3s that were right in that sweet spot for treatment.

在结束之前，我想花点时间聊聊一个相关但稍微偏一点的话题。

Before I close, I want to just sort of spend some time on a topic that is related to this, but a little bit oblique to it.

我觉得这个问题正变得越来越普遍，也确实值得我们警惕，不管是医生还是患者，都得清醒认识到当前的状况。

And I think it's also becoming increasingly prevalent, and it's generally, I think, something we need to be alarmed about, and physicians and patients alike need to be aware of given the current state.

这跟一类叫5α还原酶抑制剂的药有关。

It's the interaction between a class of drugs called five alpha reductase inhibitors.

最常见的就是非那雄胺，还有一种叫度他雄胺，它们会影响前列腺癌的筛查结果。

The most common of these is finasteride, but there's another one called dutasteride, and how they impact prostate cancer screening.

最近几年，非那雄胺的使用量暴增，主要原因是男性拿它来防脱或治脱发。

So, the use of finasteride has exploded in recent years, largely driven by men using it to prevent or treat hair loss.

事实上，我们在其他播客里已经多次聊过这种药，不管是讲脱发还是睾酮治疗，都提到过。

In fact, we've talked about this drug many times on other podcasts, both in the context of hair loss and testosterone use.

我们之前 elsewhere 讨论过非那雄胺和前列腺癌风险的问题，但我想在这里专门花点时间好好讲一讲。

We've discussed the potential risks of finasteride and prostate cancer development elsewhere, but I want to have some dedicated sections here where I talk about that.

我想重点说一个关键点：根据现有数据，非那雄胺本身并不会导致前列腺癌。

So, I want to focus on one specific issue, which is that finasteride, as far as we can tell from the data, does not cause prostate cancer.

对。

Okay.

但它绝对会显著压低PSA值，如果医生不知道该怎么调整，完全可能把癌症给遮得严严实实。

But what it absolutely unequivocally does is suppress PSA in a way that can completely mask the present of cancer if the treating physician doesn't know how to adjust for it.

来，说说背后的机制。

Now, here's the mechanism.

非那雄胺会阻断睾酮在前列腺里转化成双氢睾酮（DHT）。

Finasteride blocks the conversion of testosterone into dihydrotestosterone, or DHT, in the prostate.

前列腺里DHT一减少，PSA的生成也会跟着大幅下降。

That reduction in local DHT also dramatically reduces PSA production.

实际来看，吃非那雄胺六个月后，PSA通常会降三分之一左右，一年后差不多能砍掉一半。

As a practical matter, you can expect PSA to drop by about a third within six months of starting finasteride, and to be roughly cut in half by a year.