prostate-evidence

Enzalutamide, an oral tablet that blocks the androgen receptor at several points at once, added nearly five months to median survival in men whose cancer had already been through chemotherapy. More than half had their PSA halve, against two percent on placebo.

A short form of the androgen receptor, missing the part that the hormone drugs grab onto, can be detected in tumour cells circulating in the blood. Not one man whose cells carried it responded to either enzalutamide or abiraterone.

Black men in the United States are more likely to die of prostate cancer. This study looked at registry data, an equal-access health system and randomised trials together, and found that once treatment and access were equal, the difference in prostate cancer deaths largely disappeared. The difference in dying of everything else did not.

Prostate MRI is good at answering whether a man has a serious cancer somewhere. This study matched scans against the whole removed prostate and found it is much worse at finding every tumour: it missed at least one significant tumour in a third of men.

The trial that showed PSA screening does save lives, and showed what it costs. Screening cut the death rate from prostate cancer by a fifth, but 1,410 men had to be screened and 48 extra cancers treated to prevent one death.

The first trial to give chemotherapy at the same time as hormone therapy in newly diagnosed metastatic prostate cancer. It found no survival benefit and concluded against the approach, two years before two larger trials found the opposite.

In 1941 two Chicago surgeons showed that removing a man's testicles, or giving him oestrogen, made advanced prostate cancer shrink and his blood chemistry improve, and that giving testosterone made it worse. It was the first time any cancer in any organ had been made to regress by a drug or a hormone.

When hormone treatment stops working, the cancer often has not stopped caring about the hormone. In a third of tumours that came back on treatment, the cell had simply made extra copies of the androgen receptor gene so it could live on the tiny amount of hormone left.

Nearly one man in eight with prostate cancer that has spread carries an inherited fault in a DNA repair gene, most often BRCA2. Family history and age at diagnosis did not predict who: the only way to find them is to test everybody.

The first large look at prostate cancer across copy number, gene expression and sequence at once. Its most useful finding for patients was that the pattern of gained and lost chromosome segments separates low-risk from high-risk disease better than the Gleason score does.

Screening trials are judged on deaths, which take fifteen years to count, and on cancers found, which is the wrong direction. Preventing a man from turning up with cancer already in his bones happens three times as often as preventing a death, arrives years earlier, and is the outcome he cares about.

Checkpoint immunotherapy transformed several cancers and did almost nothing here. In 258 men with advanced prostate cancer, about 1 in 20 had a response, and whether the tumour expressed PD-L1 made no difference.

Estimates of how many screen-detected prostate cancers would never have caused trouble ranged from a quarter to more than four fifths. Three independent models were run side by side to find out why, and showed the answer depends almost entirely on how the question is asked.

This is where the number 4.0 came from. Screening 1,653 healthy men over 50 with a blood test and biopsying those above that level found cancers that a finger examination would have missed, and the threshold entered practice worldwide.

This study found the one change that always happened when prostate cancer became resistant to hormone-blocking drugs: the cell made more androgen receptor. With enough of it, the drugs that were meant to block the receptor started switching it on instead.

A review that gathered every way overdiagnosis in prostate cancer has been measured and found estimates from under two percent to two thirds, depending entirely on the method. The one figure everyone can agree on is that autopsy studies find prostate cancer in around a fifth to two fifths of men who died of something else.

Twenty-one men whose prostate cancer had already stopped responding to every hormone treatment available were given a drug that shuts off the last remaining source of androgen. Two thirds had their PSA fall, which proved the cancer had never stopped depending on the hormone.

In men whose prostate cancer was mostly found by a blood test, surgery did not significantly reduce deaths after nearly twenty years. It did cause more incontinence and sexual problems, and it did reduce later treatment for the cancer growing.

The American screening trial, published in the same issue as the European one and reaching the opposite conclusion. It found more cancers in the screened group and no difference in deaths, which is partly because half the men in the comparison group were being screened anyway.

The same drug given before chemotherapy rather than after it. At one year, 65 percent of men on enzalutamide had no sign of the cancer growing on scans, against 14 percent on placebo, and the need for chemotherapy was pushed a long way back.

Every man with a raised PSA used to get a needle biopsy through the rectum, which misses half the serious cancers and can cause sepsis. This trial gave 576 men a scan, a standard biopsy and an exhaustive mapping biopsy, and showed the scan could safely spare a quarter of them the needle.

The largest routine-practice picture of what is broken in prostate tumours. Across 3,476 samples sent for commercial sequencing, TP53 was altered in 44 percent and PTEN in 32 percent, and just over half carried something a drug is being developed against.

Counting what the blood test did to a country. In the twenty years after PSA testing began in the United States, an extra 1.3 million men were diagnosed with prostate cancer and about a million were definitively treated, for a benefit that on the most generous assumption reached one man in twenty of them.

The paper that turned a protein made by the prostate into the blood test now used on millions of men a year. It showed the level tracked how much cancer there was, fell to nothing after surgery, and rose again when the cancer came back.

Prostate MRI is good at telling you whether a man has a serious cancer and poor at telling you where all of it is. It missed at least one significant tumour in a third of men in the study that checked it against the whole removed prostate. Services that treat part of the gland, or follow men on imaging alone, are relying on the number they do not measure.

Cancer is usually described as accumulating damage one change at a time. Sequencing 57 whole prostate cancer genomes showed something else: chains of translocations and deletions that happen together in one burst, disrupting several cancer genes at once.

Metastatic prostate cancer now has six classes of treatment that work, and no trial has ever compared the orders they can be given in. Every trial adds a drug to the front; none asks what should follow it, so the sequence a man receives is decided by habit and by what was licensed first.

Gene fusions were thought to be a feature of leukaemias, not common solid cancers. This study found one in prostate cancer that joins a switch controlled by testosterone to a growth gene, and found it in most of the tumours it looked at.

When Black and white men in the United States are given the same treatment, the gap in dying of prostate cancer largely closes. The gap in dying of everything else does not. Cancer services measure the first and not the second, which means the surviving disparity is invisible to the people best placed to act on it.

Prostate cancer adapts to having almost no testosterone. This trial did the opposite of what the textbook says and gave men large doses of testosterone. Three in ten responded, and more than half responded again to the hormone-blocking drug that had stopped working.

Some prostate cancers escape hormone drugs not by changing the receptor but by becoming a different kind of cell that does not need it. This paper showed how: losing two tumour suppressors lets the cell switch on SOX2 and change identity, and restoring them reverses it.

Men with prostate cancer found because it caused a lump or symptoms, randomised in the years before PSA testing, were followed for nearly thirty years. Surgery roughly halved the chance of dying of prostate cancer and added an average of 2.9 years of life.

Three trials of chemotherapy at the start of hormone therapy had reported, two positive and one negative. Pooling them showed the treatment does work in metastatic disease, improving four-year survival by about nine percent, and that zoledronic acid does not.

One hundred and fifty men with prostate cancer that had spread and stopped responding to hormones had their tumours biopsied and sequenced prospectively. Nine in ten had a genetic change that a drug could in principle be aimed at, and one in five had a broken DNA repair gene.

Hormone therapy causes hot flushes, loss of libido, loss of muscle and bone, and low mood. This trial asked whether men could take breaks from it. After ten years the answer was uncomfortable: the breaks felt better for three months, and the trial could not rule out a worse chance of survival.

Published in the same issue as TAX 327 and reaching the same conclusion by a different route: docetaxel extends life in advanced prostate cancer. The extra drug it was paired with, estramustine, brought enough side effects that it was dropped from practice.

Giving men with castration-resistant prostate cancer large doses of the hormone the treatment has spent years removing makes a third of them respond, and makes half of them respond again to the drug that had stopped working. It has never been taken to a definitive trial, partly because the endpoint that shows the benefit is not the one trials usually use.

The first treatment ever shown to help men live longer once prostate cancer stopped responding to hormones. Docetaxel every three weeks added about two and a half months to median survival compared with the older drug, and made pain and quality of life better as well.

The Cancer Genome Atlas classified 333 prostate cancers taken out at surgery and found that three quarters fall into one of seven groups defined by a fusion or a mutation. A quarter had a change that a drug could in principle be aimed at, and one in five had a broken DNA repair gene.

About one man in eight with prostate cancer that has spread carries an inherited DNA repair fault, and about one in five has one in the tumour. The drugs for those faults have moved to the beginning of treatment, but the test is still usually done near the end, when it is too late to use the result.

By sequencing many separate deposits from ten men who died of prostate cancer, this study reconstructed how the cancer travelled. Metastases seeded other metastases, and often did it in groups of cells rather than one at a time.

Fifty men who died of prostate cancer had their tumours sequenced within hours of death. Even after years of treatment the cancers carried few mutations, and the recurring ones were in genes that control how DNA is packaged and read rather than in classic cancer genes.

Fifty men whose prostate cancer had exhausted every standard treatment were given a PARP inhibitor and biopsied. A third responded, and almost all the responders were the ones with a broken DNA repair gene, including every man who had lost BRCA2.

The largest genetic study of prostate cancer pooled 107,247 men with the disease and 127,006 without, across ancestries. It brought the number of known risk variants to 269 and showed that men of African ancestry carry, on average, more than twice the genetic risk score of men of European ancestry.

A randomised comparison of high-dose testosterone against a standard hormone-blocking drug. Neither delayed progression better than the other, but men who had the testosterone first and the drug second lived nearly nine months longer before their second progression, and felt better throughout.

The trial that got rucaparib approved for prostate cancer. In 115 men with a BRCA fault whose cancer had already been through hormone drugs and chemotherapy, around half had their tumours shrink or their PSA halve.

The randomised confirmation that a PARP inhibitor beats the alternatives in men with a BRCA fault, nearly doubling the time before the cancer grew on scans. In men with an ATM fault instead, it did nothing.

The first drug shown to extend life after docetaxel has stopped working. Cabazitaxel, a taxane designed to get past the pumps that expel docetaxel from resistant cells, added about two and a half months, at the cost of a high rate of low white cell counts.

In 2012 the American preventive services body recommended against PSA screening for every man at every age. It is the most consequential negative screening recommendation ever made, and it was reversed six years later.

Six years after recommending against PSA testing for everyone, the same body changed its mind for men aged 55 to 69 and said the decision should be theirs. The statement puts the numbers on both sides: about 1.3 deaths prevented per 1,000 men screened, and one in five who have surgery left with long-term incontinence.

In a minority of men, prostate cancer escapes hormone drugs by becoming a different kind of cell that no longer needs the androgen receptor. By the time a biopsy shows it, the treatment options are almost gone. The genetic changes that allow the switch are detectable years earlier, and nobody is looking for them.