Harvard Prostate Knowledge | Empowering you to take charge of your prostate health
Dr. Garnick is an internationally renowned expert in medical oncology and urologic cancer. A clinical professor of medicine at Harvard Medical School, he also maintains an active clinical practice at Beth Israel Deaconess Medical Center, and has dedicated his career to the development of new therapies for the treatment of prostate cancer.
After being treated for prostate cancer, some men will experience a rise in PSA levels suggesting that new tumors lurk somewhere in the body. Finding these tiny cancerous deposits before they grow and spread any further is crucially important. But it’s also a challenge, since the budding tumors might be too small to see with standard tools such as magnetic resonance imaging.
Now scientists in California have published results with an experimental imaging technique that detects recurring prostate cancer with the best accuracy reported yet. Importantly, some of the unveiled tumors were “still curable with targeted radiation therapy,” said Dr. Thomas Hope, a radiologist at the University of California, San Francisco School of Medicine, who led the study. “That’s what makes the research so exciting.”
How the test works
The technique used in the study is a modified form of positron emission tomography, or PET scanning. When performing a PET scan, doctors will first give an intravenous injection of a harmless radioactive tracer that travels through the bloodstream and attaches to proteins on cancer cells. The PET scanning technology detects this radiation, and thus allows specially trained experts to see where the cancer cells are located.
Two tracers have been approved so far by the FDA for use in prostate cancer diagnostics: one called choline C11 and another called fluciclovine-18-F. Dr. Hope’s team, however, used an alternative tracer called gallium-68, which has yet to win regulatory approval in the United States. Gallium-68 has the advantage of binding specifically to a protein called prostate-specific membrane antigen (PMSA), which is highly expressed on metastatic cells and shows up better on PET imaging than the current FDA-approved agents.
During the study, USCF researchers and their colleagues at the University of California, Los Angeles enrolled 635 men with rising PSA levels after prostate cancer treatment. The men were each injected with gallium-68, and then given a whole-body PET scan. Importantly, the images were interpreted by independent readers who had no other knowledge of a patient’s clinical status.
What it found
Gallium-68 PET scans produced positive results in 75% of the men, and the likelihood of a positive hit grew as their PSA levels increased. For instance, 38% of men with PSA levels of 0.5 nanograms per milliliter (ng/mL) or less were flagged by PET scanning, compared to 97% of the men with PSA levels of 5 ng/mL or higher.
The test’s positive predictive value (PPV) — meaning the probability that it would identify men with metastatic cancer correctly — ranged between 84% and 92%. According to Dr. Hope, PET scans from the pelvic lymph nodes had the highest PPVs, while scans of the lower ribs, which are prone to features that mimic cancer, had the lowest.
“As we gain more experience with gallium-68/PSMA scanning, we’ll lower the false positive rate and increase the test’s accuracy even further,” said Dr. Hope, who is now working with UCLA on efforts to win FDA approval for the tracer.
Racial differences have long been evident in prostate cancer statistics. In particular, African American men are diagnosed with prostate cancer more often than white men, and they’re also nearly twice as likely to die of the disease.
But new research also shows that African American men who receive the most advanced treatments for late-stage prostate cancer can live at least as long — or even longer — than their Caucasian counterparts.
Why is this the case? Scientists are searching for an explanation. “The fact that African American men have better survival is of huge research interest,” said Dr. Stephen Freedland, a urologist at Cedars-Sinai Medical Center in Los Angeles. “If we can figure this out, we’ll obtain key insights into the factors driving survival in late-stage prostate cancer. And that in turn will help spur better treatments for all men — regardless of race.”
Each year, about 160 per 100,000 African American men receive a prostate cancer diagnosis. That’s three times higher than the comparable figure for white American men, and it’s also higher than the number of black men diagnosed annually with prostate cancer in Africa. It’s possible that dietary or environmental factors — perhaps in combination with genetic susceptibilities — put African American men at greater risk in the United States. But African American men also tend to have less access to health care than white Americans, and many of them are diagnosed after their tumors have already begun to metastasize, or spread.
A surprising survival advantage
What the new research shows, however, is that survival advantages can favor African Americans who undergo treatment for advanced prostate cancer in clinical trials. One study pooled data from nine clinical trials, enrolling a combined 88,200 men with metastatic prostate cancer who were treated with a chemotherapy drug called docetaxel. The African American and white men had similar survival rates — 21 months and 21.2 months respectively. But after adjusting for factors such as age and prostate-specific antigen levels, the researchers found that African Americans were 20% less likely to have died during the course of those trials than their white counterparts.
Freedland co-authored another recent study showing that African Americans respond better to newer drugs that target testosterone, which is a hormone that drives prostate cancer to grow faster. Using data gathered by the Veterans Health Administration between 2013 and 2018, the researchers looked at how long African American and white men with metastatic prostate cancer lived after treatment with one of two drugs: abiraterone acetate or enzalutamide. They had access to records from nearly 3,000 men. The unpublished results, presented at a medical conference in February, showed that median survival among the African Americans lasted 30 months, compared to 26 months among their white counterparts. “So, the key takeaway is that if they get to advanced prostate cancer, and are treated equally in an equal access medical center, black men can have similar or even better outcomes,” Freedland said.
The data still need to be confirmed in additional research, Freedland emphasized. But in the meantime, the studies add to a growing body of evidence that’s changing how scientists look at racial differences in prostate cancer. Ideally, the research will reveal new biological insights into prostate cancer, and allow doctors to tailor treatments more effectively.
Men with advanced prostate cancer are typically treated with drugs that prevent the body from making or using testosterone. A hormone (or an androgen, as it’s known), testosterone drives prostate cancer cells to grow faster, so shutting it down is essential to keeping the illness in check. About 600,000 men with advanced prostate cancer in the United States today are undergoing this type of anti-hormonal treatment, which is called androgen deprivation therapy (ADT). But even as ADT helps men live longer, it exerts a toll on the body. Men can lose muscle and bone mass, gain weight, and they face higher risks for heart disease and type 2 diabetes.
The good news is that a few helpful strategies can lessen these metabolic side effects. Engaging in aerobic exercise and resistance training, for instance, has been shown to drop levels of inflammation in the body that might otherwise lead to heart disease. Quitting smoking is similarly beneficial, since tobacco smoke’s toxic effects on the heart are more pronounced in the absence of testosterone.
In a new study, researchers have shown that taking daily walks and eating a low-carbohydrate diet can also lessen ADT’s harms. During the investigation, 42 men who were just starting on ADT were split into two groups: Half the men took daily walks lasting at least half an hour five days a week, and were instructed to limit their carbohydrate intake to no more than 20 grams per day. The other half of the men (the control group) maintained their usual diet and exercise patterns.
After six months, typical weight loss among men in the walking/low-carbohydrate group was about 20 pounds, compared to a nearly 3-pound weight gain among men who stuck to their usual dietary and exercise routines. Men in the walking/low-carbohydrate group also had significantly higher blood levels of high-density lipoprotein (HDL), which removes cholesterol and lessens risks of atherosclerosis and heart disease. And they also had significant improvements in insulin resistance (a pre-diabetic condition), but only at three months and not when the levels were checked again three months later.
The study’s lead author, Dr. Stephen Freedland from Cedars-Sinai Medical Center in Los Angeles, California, says exercise combined with low-carbohydrate diets appears to be a promising strategy in men undergoing ADT that should be studied further. Dr. Marc Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, and editor in chief of HarvardProstateKnowledge.org, agreed, pointing out that weight gain can be a real problem for men that endures even after ADT is discontinued. “The weight loss in the experimental group is encouraging and should be validated in larger studies,” he said. “In the meantime, combining exercise with low-carbohydrate diets is a common-sense strategy that clinicians should recommend to their patients.”
Men weighing treatment options for intermediate- or high-risk cancer that is still localized to the prostate can face a tricky question. A standard approach in these cases is to give radiation to the prostate along with drugs that block testosterone, a hormone that makes the cancer cells grow faster. For how long should this hormone therapy last? That’s not entirely clear. The drugs have side effects, such as fatigue, impotence, and a loss of muscle mass. But radiation doesn’t control prostate cancer effectively without them. Doctors therefore aim to give hormone therapy only for as long as it takes to help their patients, without causing any undue harm.
Now, newly published results from a phase 3 clinical trial are providing some needed guidance.
How the study was performed
During the study, scientists randomized 1,071 men with intermediate- or high-risk localized prostate cancer into four groups. One group received radiation and six months of an anti-testosterone drug called leuporelin, and the second group received radiation plus 18 months of leuporelin therapy. Two other groups were treated with the same regimens of either radiation plus six or 18 months of leuporelin therapy, along with another drug called zoledronic acid, which helps to limit skeletal pain and related complications should cancer spread to the bones. Study enrollment occurred between 2003 and 2007 at 23 treatment centers across New Zealand and Australia.
Here’s what the results showed
After a median follow-up of just over 10 years, 9.7% of men who were treated with radiation and leuporelin for 18 months had died from prostate cancer, compared to 13.3% of the men treated with radiation and leuporelin for six months. Adding zoledronic acid made no difference in either case.
The authors concluded that hormonal therapy is more effective at preventing prostate cancer death when it’s given for 18 months rather than six. And similar benefits were noted for other endpoints as well. For instance, prostate tumors were less likely to metastasize, or spread, among men in the longer duration treatment group, and it took longer for their cancers to become resistant to hormone therapy if it was reinitiated later.
In earlier clinical research, scientists discovered that hormonal therapy given for three years protects against prostate cancer death more effectively than a six-month treatment regimen. But three years of hormone therapy isn’t easily tolerated, and evidence so far shows that 10-year survival rates after either 18 months or three years of hormonal therapy are similar, the authors of the new study claim.
“This study reaffirms what many clinicians have put into practice: longer duration hormonal therapy in appropriately selected patient populations provides a greater benefit,” said Dr. Marc Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, and editor in chief of HarvardProstateKnowledge.org. “Prior studies using three years of hormonal therapy have also shown this, but it is important to recognize that some men may have significantly delayed return of the body’s testosterone upon completion of the therapy — a fact that needs to be discussed when contemplating longer-term treatment programs.”
Statins and other drugs that lessen cardiovascular disease risk by lowering blood lipids rank among the world’s most prescribed medications. And for the men who take them, accumulating evidence has for years pointed to another added benefit: a lower risk of developing prostate cancer.
Now researchers are reporting that long-term statin use (more than 10 years) can also reduce the odds of a prostate cancer death. The new findings come from a study led by Alison Mondul, a cancer epidemiologist at the University of Michigan School of Public Health.
Mondul says that most men develop slow-growing, indolent prostate cancers that will never become clinically relevant. Her goal with this new study, she says, was to look more specifically at whether statins protect against fatal prostate cancers.
Here’s what the researchers did
Since death from prostate cancer can take many years to occur, Mondul and her team needed a dataset with an adequate duration of follow-up. And the study they went to for data — the Atherosclerosis Risk in Communities Study (ARIC) — fit the bill with a launch date of 1985. The ARIC study enrolled nearly 16,000 men and women between the ages of 45 and 64, and monitored their heart disease outcomes until 2016. Mondul’s team zeroed in on 6,518 men from the ARIC cohort who had enrolled between 1990 and 1992 — the beginning of the statin era. Approximately 25% of those men were African Americans, and none of them had prostate cancer when they entered the study.
Like all the ARIC participants, each of these men returned every three years for an extensive physical exam, during which they also supplied answers to questions about their medical history, demographic and lifestyle factors, and medication use. By 1996, 21% of the white men and 11% of the African Americans were using lipid-lowering drugs, mostly statins. And by 2012, 750 of the men had developed prostate cancer, and 90 of them had died of the disease.
This is what they found out
Mondul’s investigation showed men who used lipid-lowering drugs for more than 10 years were 33% less likely to develop a fatal prostate cancer and 32% less likely to be diagnosed with prostate cancer in the first place. Moreover, the protective benefits were similarly evident among both white and African American men.
Just why statins and other lipid-lowering drugs might protect against prostate cancer isn’t clear. Mondul says some evidence suggests accumulating lipids in cancer cells trigger altered, pro-tumor signaling. “Statins are also anti-inflammatory, and inflammation is a cancer hallmark,” she says.
More research is needed. Meanwhile, Mondul emphasizes that men shouldn’t take statins (which can induce side effects including headache, drowsiness, insomnia, and muscle aches) solely to guard against prostate cancer. “But if men choose to take a statin for cardiovascular benefits, then they should feel good about influencing their prostate cancer risk in a positive way,” she says.
If you’re a smoker looking for another reason to quit, consider this: in addition to raising your risk of heart and lung disease, as well as cancers of the bladder and kidney, smoking could boost the odds that you will develop aggressive prostate cancer that metastasizes, or spreads through your body. That’s according to research published by an Austrian team in 2018.
The evidence connecting tobacco use with prostate cancer (which tends to grow relatively slowly) isn’t as strong as it is for other smoking-related diseases. Researchers first detected the link only after pooling data from 51 studies that enrolled over four million men. Published in 2014, this earlier research showed that smokers have a 24% higher risk of death from prostate cancer than nonsmokers, but it left an open question: did the men who died from these other causes also have high-grade prostate cancers that had not yet been detected? Experts suspected that since smoking kills in different ways, some of those who pick up the habit simply may not live long enough to die from prostate cancer.
To investigate, the Austrian researchers limited their analysis to just over 22,000 men who had recently been treated surgically for prostate cancer, but were otherwise healthy. This was a smart move. By focusing on prostate cancer patients instead of just smokers and nonsmokers, they excluded the men who were at higher risk of death from competing causes.
After roughly six years of follow-up, the data told a clear story: prostate cancer patients who smoked were nearly twice as likely to die of their disease (89% higher risk) than nonsmokers. In addition, the risk that their cancers would spread was 151% higher, and there was a 40% higher risk that their prostate-specific antigen levels would rise again after surgery, signaling the cancer’s return.
The biological link between smoking and prostate cancer is not clear. The cancerous pollutants that smokers inhale are excreted to some extent in urine, which flows through the prostate. Smoking might boost levels of toxic inflammation. Or perhaps it’s not even the smoking itself, but the poor lifestyle choices that often accompany it, such as inadequate exercise, or excessive alcohol use..
“I continue to try to understand why some smoking patients are so concerned about simple modifications in diet and querying about supplements (most of which have never been proven to be of any benefit for prostate cancer patients) yet continue with their habit,” says Marc Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, and editor in chief of HarvardProstateKnowledge.org/ “The message is clear – if you have prostate cancer and are concerned about how you can modify risk for cancer progression, and you are a smoker — simply STOP.”
Localized prostate cancer that is diagnosed before it has a chance to spread typically responds well to surgery or radiation. But when a tumor metastasizes and sends malignant cells elsewhere in the body, the prognosis worsens. Better treatments for men with metastatic prostate cancer are urgently needed. In 2018, scientists advanced toward that goal by sequencing the entire metastatic cancer genome.
The newly revealed genomic landscape includes not just the active genes that make proteins, but also the vast stretches of DNA in between them that can also be functionally significant. Most of the genomic alterations were structural, meaning that DNA letters in the cells were mixed up, duplicated, or lost. A major finding was that the androgen receptor, which is a target for hormonal medications used when cancer returns after initial treatment, was often genetically amplified. That could explain why patients often become stubbornly resistant to hormonal therapies: if the androgen receptor is hyperactive, then the treatments can’t fully block its activity.
The research revealed many other sorts of alterations as well. For instance, DNA-repair genes such as BRCA2 and MMR were often defective. Cells rely on these genes to fix the genetic damage that afflicts them routinely every day, but with their functional loss, cancerous changes can follow. Cancer-driving oncogenes such as MYC were common, as were “tumor-suppressor” genes such as TP53 and CDK12, which ordinarily work to keep cancer at bay.
Metastatic prostate cancer differs from one man to another, and likewise, the frequency of these alterations varied among the more than 100 men who provided samples for analysis. By exploring the data, scientists can now develop new hypotheses for testing, and refine personalized treatment strategies to help men with this life-threatening disease.
Dividing cells face daunting challenges when replicating the billions of letters of DNA in their genomes. For instance, DNA letters in new cells can get mixed up, and then the affected genes don’t function correctly. To fix that problem, healthy cells can deploy so-called mismatch repair (MMR) genes that put scrambled DNA letters back in the correct order. But when those genes are themselves defective, then this repair system breaks down. And as a result, cells develop a progressive condition called microsatellite instability that leaves them vulnerable to cancer.
Those sorts of defects are shared by many different tumor types. The good news is that they are susceptible to the killing effects of an immunotherapy drug called pembrolizumab. The FDA approved that drug last year for all MMR/MSI-positive metastatic cancers, regardless of where they originate in the body. Pembrolizumab works by prompting the immune system’s T cells to recognize and destroy cancer cells bearing this genetic biomarker.
Earlier this year, scientists reported new findings with pembrolizumab in men with prostate cancer. Of the 839 men they evaluated, 2.5% had MMR defects and high levels of microsatellite instability. In about a quarter of the men, those defects were somatic, meaning they had been acquired after conception and were localized to the cancer. In the rest of the men, the defects were inherited and expressed by all the cells in their bodies.
This was the first study to investigate how the drug performs in men with MMR/MSI-positive prostate cancer, and the results were encouraging: Among half the treated men, PSA levels dropped by 60% to 80%. Since prostate cancer cells release PSA, a decline in the level of that hormone shows the drug is working. Moreover, tumors also shrank in as many as 40% of the men whose PSA levels were responding to treatment.
The authors of this study recommended that all metastatic prostate cancer patients be tested for these defects, since pembrolizumab might also work for them. Dr. Marc Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, and editor in chief of HarvardProstateKnowledge.org, agrees. “This is an exciting development as it opens up therapeutic possibilities that would have never been considered previously,” he said. “Moreover, our own personal experiences in testing for MMR mutations and treatment with pembrolizumab have been remarkable. Testing will likely become mandatory as more experience is gathered.”
A new procedure that relieves symptoms without causing sexual side effects
As men get older, their prostates often get bigger and block the flow of urine out of the bladder. This condition, which is called benign prostatic hyperplasia, causes bothersome symptoms. Since men can’t fully empty their bladders, they experience sudden and frequent urges to urinate. Treatments can relieve these symptoms, but not without troubling side effects: pharmaceutical BPH treatments cause dizziness, fatigue, and retrograde ejaculation, meaning that semen gets diverted to the bladder during orgasm instead of being ejected from the body. Surgical treatments such as transurethral resection of the prostate, or TURP, can relieve symptoms for many years. But they also take weeks or months to recover from, and men can experience permanent retrograde ejaculation, and in some instances, long-term impotence.
Still, it’s important to treat BPH to avoid even worse problems later. Left untreated, men can develop urinary retention, which is an acute inability to urinate without a catheter, and their bladder health can also deteriorate over time.
Now a newer BPH procedure, called prostatic urethral lift, or UroLift, provides another option. And unlike drugs and older BPH surgeries, it spares sexual functioning.
During a UroLift procedure, doctors use tiny implants and sutures to pull the prostate away from the bladder so that urine flows more freely out of the body. The procedure can be performed in a doctor’s office, and most men go home the same day without a catheter. Clinical studies have shown that symptomatic improvements hold up for at least five years, which is comparable to study results with TURP.
The FDA approved UroLift for enlarged prostates in 2013, and the American Urological Association began recommending it as a standard of care option this year. Urologists around the country are getting up to speed on the procedure, which is now becoming increasingly available. Readers should be aware that the AUA gave UroLift a “C” grade, in part because the long-term data in support of the procedure aren’t as plentiful as they are for TURP and other more invasive surgeries, which received a grade of “B.”
For more information, we spoke to Daniel Rukstalis, M.D., a professor of urology at Wake Forest School of Medicine in Winston-Salem, North Carolina. Dr. Rukstalis led the clinical trials behind UroLift’s approval by the FDA, and he’s performed the UroLift procedure on over 350 BPH patients. (For full disclosure, Dr. Rukstalis is a clinical investigator for NeoTract, the company that developed UroLift).
Q: Dr. Rukstalis, thank you for joining us. Why would a man consider UroLift offer over other BPH treatments?
Rukstalis: Well, all the available therapies can lessen obstructive urinary symptoms and minimize long-term risks to the bladder. But UroLift is at this moment the only BPH treatment that completely spares erectile and ejaculatory functioning.
Q: How good is it at improving BPH symptoms overall?
Rukstalis: Our clinical trial led to a 12-point drop on average in International Prostate Symptom Scores (IPSS). [The IPSS is an eight-question screening tool that scores the severity of symptoms such as incomplete bladder emptying, urinary frequency, and weak streams. Men treated for BPH usually have IPSS scores of at least 20.] The trial had 206 participants. And at five years, their IPSS scores were still improved by about a third and their quality of life scores were also about 50% higher than when they had the procedure.
Q: Who is eligible for a UroLift?
Rukstalis: It’s FDA-approved for men 45 and older with prostates up to 80 grams in size (a normal prostate in a man ranges between 7 to 11 grams). But my view is that UroLift works best in prostates ranging from 25 to 60 grams. About a third of men with BPH also have what’s called a “median lobe,” or a bit of prostate tissue that protrudes up into the bladder. We just completed a clinical trial showing that UroLift works well for these men too. On the basis of that study, the FDA approved UroLift for men with median lobes in early 2018. We’ll typically evaluate potential candidates with a pelvic ultrasound, which provides a lot of information about the health of the bladder and the size and shape of the prostate.
Q: What can a man expect going into the procedure?
Rukstalis: We’ll put him to sleep with intravenous propofol, which is the same anesthetic used during a colonoscopy. The UroLift implants get delivered into the prostate with a rigid metal scope that goes directly through the penis. By pulling excess prostate tissue out of the way, the implants create a channel through which urine can flow. (This YouTube video provides a good overview.) We do this as an outpatient procedure.
Q: What will he experience after the procedure is done?
Rukstalis: He can expect some transient blood in the urine and a burning sensation when he pees, but this all clears up within about three days. About 2% to 4% of the men I treat spend a few days using a catheter.
Q: Why doesn’t UroLift work for larger prostates over 60 grams?
Rukstalis: Because beyond a certain size threshold, the implants don’t open the channel well enough. Also you wind up needing too many implants, and they’re very expensive — anywhere from $700 to $1,000 each. The procedure is optimized for four to six implants and you really don’t want to use more than seven of them.
Q: This is a new procedure. How important is the doctor’s experience?
Rukstalis: UroLift is a judgment-based procedure in terms of the number of implants used and where in the prostate a doctor puts them. What I would say is that you’re looking for a doctor who’s comfortable with a cystoscope [which is a hollow metal rod with a lens used for prostate examinations]. If a doctor is comfortable with cystoscopy equipment, then he or she can adopt quite readily to the technology. And there are excellent UroLift training programs around the country for any urologist who wants to do it.
Q: What about long-term prospects? Do men need repeat treatments?
Rukstalis: We know that most men still benefit from treatment at five years. But we can’t say whether those results predict benefits at 10 years or longer. We haven’t done those studies yet, but they haven’t been for TURP and the other surgical procedures either. My view is that it depends on prostate size. Men with smaller prostates will benefit for longer durations.
Q: Does having had a UroLift complicate things for a man who might need a TURP later?
Rukstalis: Not in my experience. I’ve performed TURPs, prostatectomies, and laser prostate surgeries in people who had a UroLift with no trouble.
Q: Do you have any criticisms of the procedure?
Rukstalis: It’s too expensive. We need to find ways of doing UroLift at lesser cost. And some men find it doesn’t work as well as they had hoped, even though in these men, the procedure goes a long way toward protecting bladder functioning.
Q: Thanks very much! I’m sure our readers will appreciate your insights.
Dr. Marc Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, and editor in chief of HarvardProstateKnowledge.org also commented on the UroLift: “This is one of many emerging options for non-pharmacologic BPH treatment that can now be offered to the proper patient matched to the appropriately trained urologist. As with many procedures, longer-term outcomes are needed to determine its proper role in treating this very common problem.”
Treatments for advanced prostate cancer that’s metastasizing, or spreading in the body, are getting better, and men with the disease are living longer because of them, new research has found.
For years, the only available treatments for these aggressive tumors were androgen-deprivation therapies (ADT) that block testosterone, the male sex hormone that makes prostate cancer cells grow faster. Giving ADT slows cancer progression, but tumors typically develop resistance against it within three years and start growing again.
But then newer treatments for metastatic prostate cancer started showing up. A drug called docetaxel was approved by the FDA in 2004, followed by cabazitaxel in 2010, sipuleucel-T in 2011, abiraterone in 2011, and enzalutamide in 2012. Each of these drugs targets metastatic prostate cancer in different ways, and men who took any one of them in clinical trials lived longer than men who took ADT by itself.
For the current study, researchers set out to answer a unique question. They wanted to know if the combined market availability of these drugs was making a survival difference for men being treated for metastatic prostate cancer in the general population.
To find out, they divided men tracked by a national cancer registry into two groups. One group of 4,298 men had been diagnosed with metastatic prostate cancer between 2004 and 2008, and another equally sized group was diagnosed with the disease between 2009 and 2014. All the men in both groups were matched in terms of age, race, cancer stage at diagnosis, treatment, and other factors.
Results showed that the duration of survival before men died specifically from prostate cancer lasted approximately 32 months among those diagnosed during the earlier time frame, and 36 months among those diagnosed during the later one. Similarly, the duration of survival before men died from any cause after a metastatic prostate cancer diagnosis was 26 months between 2004 and 2008, and 29 months during the 2009–2014 time frame.
The authors acknowledge that the survival improvements are modest, but add they may not fully account for longer survival improvements from abiraterone and enzalutamide, which only came into widespread use at the end of the study period. Furthermore, men who respond extraordinarily well to the new treatments may live far longer than those who don’t. In general, the evidence provides “valid evidence in support of [newer] novel treatments,” the authors wrote.
Dr. Mark Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, and editor in chief of HarvardProstateKnowledge.org, says, “This study provides important information that men with advanced forms of prostate cancer are now living longer than they once did, sometimes years longer. Those of us who have been treating prostate cancer for decades appreciate this study’s fundamental finding that the improved longevity from newer cancer drugs is considerable.”