William came to me for a third opinion. He was 53 and healthy, with a wife and two teenage children, a busy job, and a typically hectic work-and-family schedule. He’d taken time to do the right thing and had visited his primary care provider for a routine health exam and blood tests, his first in many years. A few weeks later, he’d found himself in an unfamiliar urologist’s office, at the edge of an abyss, ears ringing with what may be three of the most dreaded words in medicine: ‘You have cancer.’ This diagnosis portends pain, suffering and death: in the United States alone, cancer kills more than 600,000 people a year, enough lives to empty a city.
Yet, receiving a cancer diagnosis doesn’t necessarily mean what it once did. William was in very broad company: more than 2 million Americans a year receive the diagnosis and, for many, the finding entails little to no threat to length or quality of life, except through the ill effects of treatments. However, patients labelled with the ‘C-word’ face substantial clinical, psychological, social and economic consequences. This disconnect – between what the word evokes in my exam room and what it often describes in contemporary practice – drives controversies and variability in screening practices, and in light of our growing understanding of cellular biology, demands that we rethink what we really mean when we apply the label ‘cancer’.
William’s cancer was in his prostate, an organ of whose existence he was previously only vaguely aware, but whose removal or radiation risked impairments to urinary, bowel and sexual function. His biopsy had revealed a prostate tumour we designate ‘grade group 1’, which features few molecular hallmarks of cancer and no immediate potential for metastasis or death. Nonetheless, beset with many competing opinions from his rapidly expanding medical team, William found himself rushing headlong toward treatment, and wrestling with a constant anxiety he’d never felt before. By the time he reached my office, he had taken medical leave from work and confided that, perversely, he was smoking for the first time in decades.
When I started medical school in the 1990s, I found cancer fascinating and terrifying exactly because of the betrayal it represented. Most human disease represents failure of one body system or another. Whether due to trauma, infection, degradation of blood supply, mechanical wear-and-tear or other causes, one or more organs stop performing optimally. In such cases, our job in medicine is simple in principle: support the failing system, prevent further damage, and repair or replace missing function as much as possible.
Cancer is fundamentally different: although ultimately it also causes system failures, its origin lies in cells in a corner of a given organ thriving more than they should, growing too quickly, and eventually exploring and colonising other parts of the body. A marauding virus or bacterium is clearly a malign invader that can be understood and labelled as foreign and hostile. A cancer is a person’s own cells. They are behaving badly but are still intrinsic to the self. Chemotherapy for cancer is so much more toxic than antibiotics for bacterial infection precisely because it is harder for treatments to consistently distinguish ‘normal’ from ‘cancer’ among a body’s cells.
The noun, the proper noun with the capital letter, still looms, menacing
In my practices at the University of California, San Francisco Cancer Center and the San Francisco Veterans Affairs Medical Center, I see men in William’s situation in every clinic, every week. The better-informed among them have often already figured out that not every tumour needs treatment, but many are still reeling from the moment the word ‘cancer’ entered the room – the way the light suddenly dimmed and the air thickened – and how little they really heard during the rest of the visit. Counselling these patients is as important and nuanced a part of my job as is surgery, and the right words in the office are no less critical than the right tools in the operating room. But even as we have developed robot-assisted precision surgical systems, increasingly focused radiation delivery platforms and marvellously targeted pharmaceuticals, our language is essentially stuck in the 19th century.
Many colleagues and I try to pepper these counselling conversations with adjectives intended to reassure both patients and their loved ones: low-grade, low-risk, nonthreatening, slow-growing, indolent. We’ve grown relatively facile using these modifiers to pull patients back from the edge of the chasm, but the noun, the proper noun with the capital letter, still looms, menacing. After many years of these patient consultations – which have grown easier over time, but only to an extent – I am among a growing cadre of prostate cancer specialists and researchers who have started to challenge our colleagues to take seriously the question of whether to update our vocabulary to bring what we say back in line with what patients hear.
My professional forebears would recognise cancer at human scale quickly and with a knowing dread: the lump in the breast accompanied by another in the armpit, the yellowed eyes indicating a squeezed bile duct, the minor bleeding that wouldn’t stop because leukaemia had taken over the bone marrow. The unintended weight loss. The nagging pain. In my time, in contrast, we typically present a patient with the diagnosis over a piece of paper or text on a computer screen: a pathology report, a divination read from glass slides and rendered in ink or pixels to predict the future for a patient who today usually feels just fine. But at what point does aberrant behaviour threaten the whole body? How do we determine the thresholds cells cross from variant to abnormality to enemy? In the decades of my career since school, our appreciation of cancer’s complexity has grown more sophisticated, but we are still nowhere near being able to define the true moment a cancer begins, nor the subsequent moment it first threatens health and life.
Medical traditions stretching over thousands of years recognised visible growths with the capacity to grow, spread and kill. Hippocrates and his contemporaries in the 5th century BCE first named the karkinos – ‘the crab’ – after the visible tendrils that progressive tumours could be seen to propagate along lymphatic channels under the skin. In the ensuing millennia, progress in understanding the disease came in fits and starts, but cancers were universally detected when they were visible, palpable or symptomatic, by which point cure with surgery was successful only uncommonly. Even when survivable in the hard-to-imagine pre-anaesthesia, pre-antisepsis era, surgery couldn’t eradicate cancer that had already metastasised; as a result, cancers recurred and progressed – and were nearly always lethal.
In the centuries after the development of microscopy, modern pathology evolved to allow researchers and physicians to see the hidden face of the adversary: the minute cells devolved from their proper roles in the broader organism and hellbent on reproduction and migration. By the late 19th century, improved microscopes allowed early pathologists to categorise cancers – carcinomas – based not just on their organs of origin but also on the appearance of the cells themselves, laying the foundation for modern grading and staging.
The unintended consequence of screening has been over-diagnosis – the detection of lesions that would never threaten survival
Even throughout most of the microscopy era, however, cancers were still first detected based on clinically apparent symptoms, and the microscopic insights were gained only after biopsy or surgery for a cancer that was usually already relatively advanced. In these decades, the pathologist largely confirmed and refined a diagnosis made – or at least suspected – by a clinician. With the advent of cancer screening in the middle of the 20th century, however, everything changed. Screening, by definition, entails looking for early cancer in otherwise healthy people. The widespread availability of Pap smears for cervical cancer (1950s), mammography and colonoscopy for breast and colon cancer (1960s) and prostate-specific antigen (PSA) testing for prostate cancer (1990s) allowed cancers to be diagnosed early, by biopsy: years or even decades before they would cause clinical problems. Over time – and without any particular intention or formal conversation – the fundamental diagnosis of cancer shifted gradually from a clinical determination by a surgeon or oncologist to a histologic determination by a pathologist, setting the stage for the rift we face today.
These years also marked the advent of the War on Cancer, and diagnosing a cancer meant treating that cancer. By the time I started training early in the millennium, screening had already saved millions of lives worldwide. However, the unintended consequence of screening has been over-diagnosis – the detection of lesions that would never cause symptoms or threaten survival if left undiscovered. As I entered practice, it was becoming clear that overdiagnosis begets overtreatment and, even as screening saves lives, it harms many others through the side-effects, sometimes permanent and occasionally lethal, of unnecessary surgery, radiation and other treatments. Moreover, the diagnosis may also mean increased costs for life and health insurance, and remains associated with increased rates of depression and even suicide. So screening has proved highly controversial, driving vitriolic debates among healthcare researchers, particularly between generalists and specialists, and wild pendulum swings in screening recommendations and practices.
Cancer screening has evolved in concert with a revolution in molecular medicine. Our society’s massive investment in research over the past half-century has paid tremendous dividends. We now enjoy an unprecedented understanding of the process of carcinogenesis and of the spectacular complexity of the arms race happening every day – in William’s body, in mine, in yours, and in every animal’s – between the reproductive and evolutionary goals of individual cells and those of whole organisms. What we now understand about cancer’s origins, evolution and outcomes should drive a reconsideration of which individuals really need to bear the diagnosis.
The irregular clusters of cells we term ‘cancer’ based on their microscopic appearance are growing at all times in every body. To understand why the overwhelming majority of these are harmless, we need to return to the early history of life on Earth. Single-celled organisms emerged just about as soon as the planet became habitable, and for the next inconceivably long stretch of 2 billion years, these cells vied for survival and evolved innumerable strategies to outcompete – and sometimes consume – their neighbours and to adapt to new habitats. Eventually, evolutionary pressures drove some groups of cells to work closely together, until they started reproducing as multicellular organisms; these newly specialised cells could contribute specific functions to the life of the organism and, critically, could no longer survive on their own.
Nearly two centuries ago, the cell theorist Matthias Schleiden observed that ‘each cell leads a double life: an independent one, pertaining to its own development alone, and another incidental, insofar as it has become an integral part of a [whole].’ This tension between independence and cooperation underlies all multicellular life – and explains a cell’s fragile pact with the body. A human being contains trillions of cells, each built around the same inherited DNA coding. These cells communicate constantly with each other – and with trillions more nonhuman bacterial and fungal cells that also comprise a healthy body – through myriad local and distant signals, regulating each other’s behaviour and growth, cooperating to maximise the reproductive success of the whole person.
And yet, every one of these cells carries the genetic memory of its single-celled past and its ancient imperative to replicate. In fact, each is kept in line only though a bewilderingly complex set of internal genetic controls and external interactions with other cells. Even after an adult stops growing, about 1 per cent of cells – billions – wear out and need to be replaced every day through cell division, requiring production of a complete and preferably perfect copy of the DNA.
I am stuck explaining cancer as we now understand it biologically to patients who still understand it culturally
Our DNA is continuously assaulted by radiation; environmental pollution; and inflammation driven by unhealthy diets, smoking, chronic stress and other factors. Furthermore, every time a cell divides, thousands of copying mistakes occur. Proofreading mechanisms correct the vast majority of these, yet errors do slip through. This imperfection is critical for a whole species, for without some rate of mutation, evolution would not be possible. For an individual, on the other hand, mistakes can be deadly. A relatively small number of uncorrected mutations can send a cell hurtling toward unfettered growth. This happens daily, in every animal.
The body monitors for such rogues; early identification and eradication of genetic uprisings is a fundamental job of William’s immune system. The arms race unfolds in every hour of every day: individual cells in some part of the body start to grow too quickly or in the wrong pattern, and immune cells identify and kill them. The odds are stacked against any one aberrant cell, but over the course of years, among billions of false starts, some mutations evade detection, take hold, and propagate. Most of these early events, however, do not define a clinically meaningful cancer in that they have no ability to cause symptoms or to spread.
Over time, some tumours acquire mutations that allow cellular growth to accelerate and others that impair error-checking. With enough regulatory signals removed, cells return to their primordial imperative to reproduce and spread. Evolution at micro-scale will favour those that can propagate fastest and travel farthest, no matter the cost to the organism as a whole. For breast gland cells, for example – whose one job is to sit in place and produce milk – to migrate into lymphatic and blood channels and thrive in the unfamiliar environments of bones or lungs requires many changes to their originally programmed behaviour. All along the way, the immune system will continue to contain, if not eradicate, incipient tumours. Only those rare exceptions that learn to grow indefinitely, travel and evade the immune system threaten the organism; these are the lesions that merit the historical and cultural terror carried by the word cancer.
Yet the huge scientific progress we have made has not translated in the public vernacular. As a physician, I am stuck explaining cancer as we now understand it biologically to patients who still understand it culturally. Biologic explication cannot fully supplant historical resonance, and translation goes only so far.
The process of carcinogenesis represents a molecular continuum. Cells acquire their first mutations without any visible changes under the microscope. Eventually, enough changes accumulate that a microscopically visible neoplasm (‘new growth’) emerges and, at some point after that, the neoplasm might acquire the capacity for metastasis. In some types of cancer, this happens frequently and very quickly; in others, it happens slowly, if at all. Critically, the appearance of a symptomatic or otherwise clinically detectable tumour may happen before or after the first cells metastasise – which is the reason screening is critical to identify potentially lethal cancers within the window of opportunity for cure.
William’s decision to undergo screening for prostate cancer, setting off the cascade that landed him in my office, is a perfect example. By the time a prostate cancer causes symptoms, it is nearly always too late to cure it, and dying of prostate cancer is both painful and protracted. Therefore, when PSA – a noninvasive blood test – hit the market in the 1990s, it was widely adopted. Diagnosis rates skyrocketed for prostate cancer, which for years has been by far the most common cancer diagnosed among men in the US and other countries. Many otherwise lethal cancers were found and cured, and prostate cancer mortality rates fell by half.
These findings are so common that the term ‘incidentaloma’ has joined the clinical vernacular
By the time of my residency training, however, there was little question that, for every death prevented through surgery and radiation, multiple non-threatening cases like William’s were detected through biopsy and were still treated aggressively. Of the many men thus overtreated, far too many suffered long-term side-effects. In part because of this problem of overdiagnosis, in 2012 the US Preventive Services Task Force recommended against any routine PSA-based screening. This recommendation had the intended effect of reducing prostate cancer overdiagnosis, but also drove an increase in mortality rates, particularly for Black men, reversing a 20-year decline. I met medical students who had been taught that PSA was the paragon of a bad screening test, and I began to see more men with incurable tumours who had never been offered one – or worse, had been refused a test even when they’d asked for it.
Grade group 1 prostate cancer – the lowest-grade form, with no immediate potential to spread or cause death – is exceedingly common. Among men who die in their 70s or 80s of non-cancer causes, these cells are found on autopsy in about half; among men in their 30s, the figure is about 20 per cent. They are not clinically meaningful cancers and may be better understood as a feature of normal male ageing. William’s low-grade prostate cancer was detected because he underwent an appropriate mid-life PSA screening, but it had likely been present for years before and was still many years away from threatening his life.
In addition to the many cancers detected through explicit screening, another large proportion are detected today more or less accidentally. I may order a CT scan for a patient with pain suggestive of a kidney stone, only to find that in addition to the stone there is an abnormality in the kidney, liver, pancreas or some other organ. These findings are so common that the originally tongue-in-cheek term ‘incidentaloma’ has worked its way into the clinical vernacular. Finding such lesions is occasionally fortuitous. I once took care of a young patient whose life was saved by an amoebic infection he picked up while travelling in South Asia; had he not been imaged for unrelenting abdominal pain, we likely would not have discovered his large, high-grade kidney cancer before it was too late. Much more often, however, we find and aggressively treat small lesions that would never have caused any problem if left undiagnosed, no matter their appearance under the microscope.
Public screening debates have grown bitter and tribal because both sides believe they are protecting patients from different versions of catastrophe. The surgeon, the oncologist and the advanced cancer patient see the metastases, the pain, the missed window, the death. The primary care physician or public policymaker sees the complications of treatment, the permanent declines in quality of life, the needless anxiety, and the costs. Both are reacting to real suffering, but the latter narratives more easily diffuse into intangible statistics, whereas the former resonate more powerfully and feel less forgivable. One patient asks: ‘Why did you talk me into the radiation that has left me with permanent bowel problems?’ while the other demands: ‘Why didn’t you order a simple test that could have saved me years of pain and let me watch my grandkids grow up?’
I regularly see both situations: patients suffering devastating side-effects of treatment they never needed, and others with incurable cancers that could have been found much earlier – some of whom had even asked for a screening test and were refused. My reservations about overdiagnosis and overtreatment have not made me a screening sceptic, but a screening test today should be only the first step on a possible journey to a diagnosis. William’s slightly elevated PSA should have prompted one of a dozen blood, urine or imaging tests designed to predict the presence or absence of potentially lethal prostate cancer. A negative test implies either a normal prostate or a grade group 1 cancer, and in either case we forego the biopsy – telling the patient more or less explicitly that if there is only low-grade disease present, both we and he are perfectly happy not knowing about it.
For the latter, the right path is active surveillance – deferring treatments and following carefully with every expectation of cure if there are signs of progression.
This paradigm was pioneered at my centre and a few others nearly 30 years ago, but has only recently gained traction in community practice, and implementation is still highly variable. In the US, too many financial, legal and cultural factors favour treatment over observation, a somewhat embarrassing reality to acknowledge in counselling visits.
We neither need nor want to know about every over-eager cell with the desire to grow but without the toolkit to travel
By the time William had his first visit with me, he had already been booked for surgery at one hospital and strongly pushed toward radiation at another. Many patients I meet in exactly this situation simply cannot get past the word, the diagnosis; they cannot reconcile with the idea that I would not want to treat what they see as a life-threatening diagnosis. Despite my best efforts at reassurance, none of my adjectives can tame the noun ‘cancer’, and too many patients wind up finding another doctor to offer unnecessary treatment.
Other examples abound. Basal cell carcinomas of the skin are so pervasive that cancer registries do not even track them. They can almost always be cured by simple excision. If neglected, they can grow quite large and can be disfiguring, but almost never spread, despite the carcinoma label.
Ductal carcinoma in situ of the breast by definition does not invade, and recent trials have suggested at least some such lesions can be monitored much like low-grade prostate cancer. In the case of thyroid cancer, pathologists have already crossed this bridge. A subset of lesions once classified as thyroid carcinoma were renamed ‘noninvasive follicular thyroid neoplasm with papillary-like nuclear features’ – mercifully abbreviated to NIFTP – because they don’t justify the full weight of ‘carcinoma’. Likewise, some small, low-grade bladder lesions once called cancer are now labelled ‘papillary urothelial neoplasms of low malignant potential’.
At the same time, we may be careening toward a new, fraught era of accelerated overdetection. All screening efforts to date have emerged from organ system-specific tests. Now, commercially available whole-body MRI scans marketed to the ‘worried well’ – and well-off – will surely multiply the number of incidentalomas we find every year. In parallel, so-called multi-cancer early detection tests promise to reveal molecular signals – fragments of DNA – of many cancers from a single blood draw. If they work well, they may save lives. But they also raise the stakes for the question that screening has already raised: when detection moves backward along the cancer journey from palpable lump, to abnormal cells, to molecular harbingers, what exactly are we naming? We neither need nor want to know about every slightly over-eager cell with the molecular desire to grow but without the genetic toolkit required to travel.
If the borders around ‘cancer’ are blurry, the boundaries of ‘normal’ are too. Normal-appearing cells often feature many cancer-typical mutations. Biology operates across bell curves, and clinical risk follows suit. In short, we don’t need to designate a given abnormality a cancer to justify treatment. We routinely remove colon polyps that may or may not presage cancer because the risks are typically negligible. In a more extreme example, some women with inherited BRCA mutations elect prophylactic mastectomy and oophorectomy – major surgery with substantial quality-of-life implications – because the spectre of possible future lethal cancer looms so darkly.
Medicine’s Greek and Latin shibboleths long served physicians better than patients. Dubbing a newly described but not-yet-understood region of the brain locus coeruleus lent an air of authority that ‘blue place’ would not have done. Today, our understanding of disease has grown along with our commitment to patient autonomy. But a very recent development in this vein, open medical records, exposes patients to language they may not understand. The result is that, all too often, the ‘you have cancer’ moment is lived only by a patient alone with a screen.
When I perform biopsies, I try to forewarn patients of the language they may see on the pathology report before we talk again, but there are limits to how much I can explain in advance. This problem is all the worse because we cancer specialists inhabit a borderland our vocabulary has not yet evolved to govern. The binary language of ‘normal’ vs ‘cancer’ suited the long epoch in which disease announced itself clinically but is badly strained in an era in which screening tests and incidental scans identify biological possibility long before clinical destiny. Pathologists describe what they see through the microscope, but a diagnosis is more than a description. When a word rises off a pathology report, whether into my exam room or the patient’s living room, it becomes prognosis, identity, fear, crisis.
Screening offers a transformative opportunity but can be implemented safely across populations only if we can distinguish and name ‘real’ cancers – those with the ability to spread and kill – as separate from the pretenders. Researchers and oncologists alike often speak of distinguishing ‘kittens’ from ‘lions’. Some kittens may evolve into lions, but these are the minority and can usually be identified before the lion escapes the enclosure.
We shouldn’t embark on a needless civil war against these minor malcontents
Modern medicine loves classification yet falls oddly short in oncology. Our international system for diagnostic coding recognises 18 codes in the heading of ‘contact with other nonvenomous reptiles’ yet only a single code for the huge spectrum of biology that is prostate cancer, regardless of aggressiveness or clinical relevance. If we’re not careful naming the boundary between abnormality and disease, then we risk wounding our patients with the name ‘cancer’ itself.
In 2026, then, should my colleagues really have handed William a cancer diagnosis? Am I required to validate that diagnosis when everything we have learned over a quarter-century screams otherwise? Increasingly, we can tell the lions from the kittens. But after thousands of years, the karkinos still looms large in cultural memory, and the term ‘carcinoma’ on a pathology report still connotes pain, loss and death. I still meet patients who book appointments specifically to set up surgery and look at me with incredulity at the suggestion that that would be the wrong first step.
Perhaps it is high time for the medical community to reconsider how we define cancer, and to bring the diagnosis back into line with enduring public perception. Cancer, in the sense that has always haunted the public imagination, spreads and kills. Precursor lesions – molecular or pathological – are not ‘normal’, but we have no shortage of alternative vocabulary with which to label them, as well as the tools to safely follow them. Most will never amount to any meaningful insurgency, and we shouldn’t embark on a needless civil war against these minor malcontents. If we permanently address overdiagnosis by simply declining to diagnose low-grade lesions, we can screen much more broadly and with greater confidence. Such a change would improve trust between patients and their doctors, and between primary care providers and their consulting specialists. Relabelling would also very likely save thousands of lives.
William needs attention to his prostate no matter what labels we hang on it. He needs my counselling and monitoring. Someday, I may need to guide him toward treatment. But what he did not need, on the day he walked into my office having already rearranged his life around a word, was to live in the full shadow of a disease that was not yet threatening him. Revising the label would not only reduce overtreatment but would also finally realign our language with our science, with our systems of classification and with patients’ lived reality. Cancer is a cellular rebellion that spreads and kills. The rest of the microscopic borderland deserves a different, gentler name.