A little known side effect with a huge impact

Why We Urgently Need To Start Screening For Prostate Cancer

Pressure is building on health service decision-makers to take action on prostate cancer screening. Prostate Cancer Research has launched a landmark report making a strong economic case for wide-scale testing.

The leading UK's charity for prostate cancer presented their findings at a celebrity-packed event at the House of Commons last month.

Wes Streeting, the Secretary of State for Health and Social Care, shared a platform with Conservative MP James Cleverly and Oscar-winning director Sir Steve McQueen and all three spoke passionately about their determination to improve early cancer detection.

Talking to an audience that included Gary Lineker, James Corden and Claudia Winkleman, Sir Steve told how he lost his father to the illness. In a powerful speech, he said his resulting vigilance and ability to fund his own health tests revealed that he too had developed the condition.

Among the high-profile figures was Nick Jones, the founder of the Soho House members club empire. Jones was diagnosed in 2022 and is a trustee of Prostate Cancer Research. His openness about his illness and its side effects has helped change the national conversation around the disease.

Soho House founder Nick Jones has been open about his prostate cancer diagnosis - Jamie Lorriman

Prostate cancer is the most common cancer in men in the UK, with approximately 55,000 new cases reported every year. Around 12,000 men die from prostate cancer annually compared to around 11,400 women killed by breast cancer.

Prostate Cancer Research says technology has moved on to the point where the cost-benefit justifications for a national programme of testing are beyond question. The Government, they say, needs to update its policy – fast.

The current position is anyone over 50 can ask for a PSA blood test. The NHS website says: "PSA tests are not routinely used to screen for prostate cancer, as results can be unreliable." But that position is being reconsidered. Alongside the evidence presented by Prostate Cancer Research, Sir Chris Hoy, 48, revealed that he was diagnosed with incurable prostate cancer last year. His case exposed the possible consequences of discovering the disease too late.

The new report from Prostate Cancer Research argues that screening technology is becoming cheaper and more effective while late-stage cancer treatments are becoming more costly. A five-year screening programme for high-risk groups 45-69 could result in a positive impact of £54 million, it says. The report points out that a 55-year-old man diagnosed at Stage 1 will cost society £0.9 million over a lifetime whereas the same man diagnosed at Stage 4 will cost closer to £2 million.

Oliver Kemp, the chief executive at Prostate Cancer Research, says: "The evidence is already there. With the tools we already have, screening would save a lot of lives. If you focus on really specific groups it saves you the £120,000 per person for late-stage treatment costs. We're allowing people to die and it's costing us money."

The charity is asking for a screening programme for high-risk groups aged 45-69 (black men and men with a family history of the disease) using currently available technology. They also want trials of new and already promising tests that can improve the accuracy of diagnosis and for that to lead to screening of the wider general population 50-69. These tests are currently both expensive and in need of large-scale data but could hugely impact the accuracy of screening if they were ramped up.

Even without more advanced tests, the arguments against prostate screening with current approaches and many of the fears about testing, are out of date, according to experts in the field.

Why we haven't had a national prostate screening programme to date?

If a man were to ask for a prostate cancer test the standard first blood test would be to check for levels of PSA (prostate specific antigen) in the blood. For men aged 40-50, a test result over 2.5 nanograms of PSA per millilitre of blood requires further investigation. But the test is imperfect.

Nick James is a professor of prostate and bladder cancer research at the Institute of Cancer Research and the Royal Marsden Hospital in London. He explains: "Men without prostate cancer could have a raised PSA and some men with really nasty cancer won't have a raised PSA at all. PSA is a protein produced by prostate tissue and its normal function is to help liquefy semen. It's meant to be there."

Cancer cells cause PSA to rise. "If you have a cancer in your prostate the blood supplies grow haphazardly and they leak, so more PSA leaks into the blood supply."

However, small early cancers do not produce very much PSA and other factors such as ageing can raise PSA without indicating cancer at all.

In the past, a raised PSA would be followed up by an ultrasound which, Prof James says, is a poor way to locate the cancer within the prostate. These would then be followed up by a biopsy because so little information could be gleaned from the scan. Biopsies involve hollow needles being inserted into the gland. "In the past you had a transrectal biopsy, entering through the rectum, and that meant a risk of introducing faecal bugs into the prostate. There was a significant infection rate from that and a not insignificant death rate from sepsis."

Given the ambiguity of the result and the risks of follow-up testing, the decision not to offer screening was the correct one, Prof James says. However, the picture is very different now.

The MRI game-changer

The transformative innovation was the switch from ultrasound to MRI scans in conjunction with the initial PSA blood test. The MRI scan is non-invasive and has a high degree of accuracy. MRI goes a long way to compensate for the vagaries of the PSA.

Prof James also points out that even in isolation the PSA is no more or less imperfect than other comparable screening technologies. "Generally speaking, you have to screen about 300 men to stop one man dying from prostate cancer. That's about the same as mammography to stop one woman dying of breast cancer. It's rather less than bowel cancer screening. As a screening test it performs as well as breast cancer and better than bowel cancer."

MRI scans mean a big reduction in the number of needless treatments, "Once you put MRI in the mix you can identify with a high degree of probability areas in the prostate likely to contain the cancer and also whether it's a clinically significant cancer that you want to treat. If you look at the people in our clinic now with a high PSA, for half of them there's such a low risk of having anything that matters, we're not even going to biopsy them at all," says Prof James.

The much-feared biopsies are now safer. The vast majority are no longer undertaken via the rectum. The standard approach is now to go in via the perineum. Prof James says: "By doing biopsy through the perineum the risk of sepsis is massively reduced. It's about as painful as having a filling. People come in, have the biopsies and go home, it's usually a day procedure."

Kemp would like a new generation of blood and saliva tests developed to the point where they can be introduced between PSA and MRI. "We are asking the Government to roll out reflex tests (follow-up tests which use the biomarkers of cancer) and build up the evidence base. These tests have close to 90 per cent sensitivity. If you add in another filter you reduce over-treatment and over-diagnosis. We met one tester last week who has a product that is 99 per cent accurate."

Men are reluctant to request a PSA test but will go if invited

He also says moving from offering tests to inviting men for tests will transform awareness and the numbers reached by the health system. "The number of black men (a high-risk group) who are aware they are more vulnerable to the disease has only risen from 24 per cent to 31 per cent over the last 10 years. We are not doing well at awareness."

Men can be reluctant to ask for a medical test but are very willing to answer an official invitation. "My grandfather never went to the doctor in 60 years but would have done so if he'd been told to. In our research, 80 per cent of black men told us they'd be willing to go for a test if invited." Eventually, however, Kemp would like to see all men over 50 invited for screening, once the new biomarker tests are in place.

The Government is listening. A spokesperson for the Department of Health and Social Care spokesperson says: "Prostate cancer patients are waiting too long for diagnosis and treatment, and we are determined to change that. The UK National Screening Committee is actively looking at all the evidence for prostate cancer screening programmes including targeted approaches for those at higher risk such as people with a family history."

The UK National Screening Committee examines all screening opportunities and makes recommendations to the Government. It is made up of experts and is currently chaired by Sir Mike Richards, a professor and practising physician for over 20 years, prior to taking up roles in industry bodies including serving as the Chief Inspector of Hospitals.

A body of evidence is mounting and those in charge of policy are being asked to make prostate cancer screening as much a part of life for men as breast cancer screening is for women. The Lancet Commission on Prostate Cancer published earlier this year predicted rising case numbers around the world. The clock is ticking on this crucial area of health policy.

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Treating Prostate Cancer With Novel Platinum Complex Via Targeting Androgen Receptor Signaling

Prostate cancer remains a global health challenge, ranking as the second most commonly diagnosed cancer among men. Although treatments like androgen deprivation therapy have been effective for early-stage prostate cancer, advanced stages, such as castration-resistant prostate cancer, present significant treatment challenges due to resistance to therapies. Current approaches targeting androgen receptor (AR) signaling, such as taxanes and newer agents, show limited success. Cisplatin, a widely used anticancer drug, has been used in combination therapies but its use is limited by severe side effects, including renal toxicity, highlighting the need for safer and more effective treatment options.

In a recent study published in Volume 63, Issue 44 of the journal Inorganic Chemistry on September 11, 2024, a team of researchers led by Associate Professor Yoshihisa Hirota from Shibaura Institute of Technology (SIT) and Professor Seiji Komeda from Suzuka University of Medical Science, explored the potential of azolato-bridged dinuclear platinum(II) complexes (azolato-bridged complexes) in treating prostate cancer. The study particularly focused on a complex called 5-H-Y ([{cis-Pt(NH3)2}2(μ-OH)(μ-tetrazolato-N2,N3)](ClO4)2) as an alternative to cisplatin. These complexes are characterized by their water solubility and promising antiproliferative effects against prostate cancer cell lines, with minimal toxicity compared to traditional platinum-based drugs.

"The first platinum-based drug, cisplatin, has a powerful effect on cancer by binding to nuclear DNA, but it also affects normal cells and can cause serious side effects. We had data showing that some azolato-bridged complexes inhibit AR signaling, which is extremely important for prostate cancer proliferation, in addition to the anticancer effect initiated by the DNA-binding. Therefore, this study was conducted to clarify the mechanism of AR signaling inhibition by the azolato-bridged complex, 5-H-Y..," explains Dr. Hirota.

The team used a variety of methods to evaluate AR dynamics and therapeutic effects in LNCaP prostate cancer cells. They utilized azolato-bridged complexes, cisplatin, and the AR antagonist KW-365 to explore their efficacy and performed cell viability, gene expression, and protein analyses. Additionally, the team employed immunofluorescence staining to visualize AR expression and evaluated apoptosis (programmed cell death), cell cycle distribution, and nuclear platinum accumulation.

The results showed that 5-H-Y exhibited significantly stronger cytotoxic effects than cisplatin, with a low half-maximal inhibitory concentration for dihydrotestosterone (DHT)-induced cell proliferation. Moreover, 5-H-Y effectively suppressed the expression of AR-responsive genes, such as PSA and TMPRSS2, and induced apoptosis in AR-overexpressing cells. Immunofluorescence analysis confirmed that 5-H-Y promoted chromatin fragmentation, a hallmark of apoptosis, with greater efficacy observed at higher concentrations.

Mechanistically, 5-H-Y was found to bind directly to AR and DNA through both noncovalent and covalent interactions. This binding induced conformational changes in AR, potentially disrupting its function. Additionally, 5-H-Y arrested cell cycle in the G2/M and sub-G1 phases, leading to apoptosis, particularly in AR-overexpressing cells. This multimodal mechanism of action distinguished 5-H-Y from cisplatin, which primarily targets DNA.

Despite its high antiproliferative activity, however, 5-H-Y demonstrated lower acute toxicity in vivo compared to other platinum complexes, making it a promising candidate for further development. "The azolato-bridged complexes used in this research are expected to play a key role in developing new treatments for advanced prostate cancer. For patients whose cancer has become resistant to conventional therapies, these complexes have the potential to effectively inhibit cancer progression with multi-layered attack while minimizing side effects. Our approach could thus expand treatment options for prostate cancer and improve the patient's quality of life," concludes Dr. Hirota enthusiastically.

Overall, the results suggest that dinuclear platinum(II) complexescould offer a more targeted approach to treating prostate cancer, specifically by inhibiting AR-mediated cell growth and survival, paving the way for the development of new, more effective therapies for advanced prostate cancer.

What To Know About Complementary Therapies For Prostate Cancer

For people battling prostate cancer, the fight can feel like a contest between the disease and the doctors. Their body is the battlefield, but they may nonetheless feel marginalized—more bystander than active participant.

"People sometimes feel like they've lost control of their own body," says Lynda Balneaves, a professor in the University of Manitoba College of Nursing in Winnipeg, who studies the role of complementary and alternative methods (CAM) in cancer care. "Complementary therapies are a way to feel engaged; they're something people can pursue on their own to regain a sense of control."

By some estimates, 87% of individuals with cancer have tried at least one form of CAM. While patients may pursue these therapies in the hopes of slowing or reversing the course of their disease, they may also look to complementary or alternative medicine for help managing the symptoms and side effects of their prostate cancer treatment. "Chemotherapy and surgery and drug therapies all produce side effects, and sometimes we as healthcare professionals don't do as great a job managing those side effects as we do treating the disease," Balneaves says.

Since it's likely their patients will pursue complementary therapies during the course of their treatment, care providers can play a supportive role by steering people toward evidence-based therapies and away from remedies that may be a poor use of time or money—or potentially even dangerous. "There are potential adverse interactions with some CAM treatments, and so we want to help individuals keep safety front of mind," Balneaves says.

Here, she and other experts describe the complementary therapy landscape for people with prostate cancer.

The 'Prostate 8'

For a 2017 review in the World Journal of Urology, a team of researchers from Harvard Medical School and the University of California, San Francisco, examined dozens of epidemiological studies in an effort to determine whether lifestyle factors could influence the progression of prostate cancer, if employed along with traditional medical and surgical intervention, not in place of them. They found evidence that eight healthy lifestyle modifications were associated with a decreased risk of cancer progression. The adoption of these lifestyle factors, which the study team nicknamed the "Prostate 8," appear to be a safe and potentially effective way for people with cancer to improve the course of their treatment.

Read More: Why Are So Many Young People Getting Cancer? It's Complicated

"The key take-home message from this work is that there is likely a series of lifestyle practices that, individually, have modest effects, but collectively may have a significant benefit," says Dr. Charles Ryan, a member and attending physician at Memorial Sloan Kettering Cancer Center in New York City, who was not involved in the study but is very familiar with its findings. If patients are looking for safe ways to improve their odds, he says these are a great place to start. "I would advise physicians treating this disease to appreciate the metabolic nature of prostate cancer and the beneficial role of lifestyle modification."

Here's a rundown of the Prostate 8, beginning with the lifestyle factors that appear to matter most:

Exercise Vigorously

Regular bouts of vigorous physical activity—defined loosely as exercise that causes sweating, as well as increased heart rate and breathing—have been found to significantly reduce a patient's prostate cancer risks. Men who, following diagnosis, increased their physical activity to three or more hours per week of vigorous activity enjoyed lower risk of death from the disease than those who reduced their vigorous physical activity following diagnosis, research has found.  

Don't Smoke

"Smoking increases risk of aggressive prostate cancer and prostate cancer-specific mortality," the Prostate 8 researchers found. "Smokers consistently have a higher risk of prostate cancer progression, including biochemical recurrence, metastasis, hormone-refractory prostate cancer, and prostate cancer-specific mortality." They recommended that people with prostate cancer avoid all tobacco products. (The same, of course, is true for people without prostate cancer.)

Replace Saturated Fats With Vegetable Fats

Swapping saturated fats such as butter for healthy sources of vegetable oils (such as olive oil and nuts) seems to be protective. "One study reported that consuming high amounts of fat from vegetable sources after diagnosis of non-metastatic prostate cancer was associated with lower risk of developing lethal disease," the Prostate 8 team wrote.

Read More: 6 Health Myths About Oils

Eat Cruciferous Vegetables

The consumption of broccoli, cauliflower, kale, brussels sprouts, and other cruciferous vegetables produces metabolites that may slow the growth of cancer cells and provide beneficial effects. One study in the International Journal of Cancer found that men with prostate cancer who ate a lot of cruciferous vegetables (roughly six servings daily) had a lower risk of progression than men who ate less than one serving per day of these vegetables.   

Consume Cooked Tomatoes

Eating at least two servings of cooked tomatoes—from sautéed or roasted tomatoes to tomato soup and pasta sauce—seems to be protective against the development of aggressive forms of prostate cancer. Eating these cooked-tomato foods with fats (like olive oil) may help the body absorb the tomato's healthy antioxidants. 

Eat Fish

"Two servings of fish per week after diagnosis was associated with a 17% lower risk of prostate cancer recurrence," wrote the Prostate 8 team, citing a study in the journal Cancer Causes and Control. As with many other studies of healthy fish intake, the researchers recommended eating fatty fish like salmon, sardines, mackerel, and herring.

Avoid Processed Meats

A lot of work has linked the consumption of processed red meat (salami, bologna, sausage, bacon, etc.) to increased mortality and illness. There's also evidence that these meats can contribute to the development and progression of prostate cancer. Several studies have looked directly at the effect of processed red meat intake after a prostate cancer diagnosis. While they did not find a significant effect, both found outcomes tended to be worse among men who ate these foods frequently. 

Avoid Whole Milk

One study in The Journal of Nutrition of men diagnosed with prostate cancer found that those who drank more than one serving per day of whole milk had a significantly increased risk of disease progression to fatal cancer compared to men who drank less than half a serving per day. "In contrast, consumption of low-fat dairy foods has not been consistently linked to adverse outcomes after a prostate cancer diagnosis," the Prostate 8 team wrote. 

While the research on these eight lifestyle changes is ongoing, and the data supporting some of them are not robust, Ryan says these are nonetheless safe changes patients can make that, together, appear to help lower their risks for deadly disease. 

Reducing the Burden of Side Effects

Along with lifestyle changes that may affect the disease's progression, a number of complementary therapies may help patients with prostate cancer address the symptoms of their disease and the side effects of treatment. 

Here, it may be helpful to break down these therapies based on the symptom or side effect they may help to relieve.

Pain

"We have found that acupuncture, acupressure, and reflexology have all been helpful with general cancer-related pain," Balneaves says. One 2019 investigation in JAMA Oncology found moderate evidence that "acupuncture and/or acupressure was significantly associated with lower pain intensity in patients with cancer compared with a sham control." Research has also found that foot reflexology—a type of foot massage—was effective in reducing pain among cancer patients. 

Fatigue

"Fatigue is a huge issue for prostate cancer patients, especially post-treatment," Balneaves says. "Exercise, as much as a person's able to, does seem to alleviate fatigue." There is also evidence that mindfulness meditation, as well as movement therapies such as yoga and tai chi, may help reduce fatigue and improve sleep among cancer patients, she says.

Read More: Why Some Men Keep Their Prostate Cancer a Secret

Anxiety and Depression

Both mindfulness practices and relaxation therapies seem to help people with cancer manage any resulting anxiety or depression, Balneaves says. For example, progressive muscle relaxation therapy—an intervention that involves systematically tensing and then relaxing the body's muscles—was found to reduce anxiety and depression in patients with prostate cancer, according to research in Evidence-Based Complementary and Alternative Medicine. "We've also found that aromatherapy, specifically lavender, can help some people with anxiety," she says. 

Sleep

Research has found that some of the interventions mentioned above—such as regular exercise and healthy eating—can help improve sleep among people with prostate cancer. Yoga and other movement therapies may also be helpful for prostate cancer patients who are struggling to sleep, Balneaves says. 

The Shaky Role of Supplements

Patients with prostate cancer frequently show interest in supplements—from vitamins and minerals to more exotic pills and powders. "There are a lot of supplements out there that people want to know about," Balneaves says. "The problem is that it's hard to get funding for studies on these supplements."

She says the research that does exist is a bit of a mixed bag. "There's been some work looking at pomegranate extract, for example, that shows it does seem to impact important biomarkers and lengthen PSA doubling time," she says. "But then a large clinical trial didn't show the same beneficial impact."

These sorts of conflicting findings are commonplace when it comes to supplements. "There's been interest in green tea, and also in lycopene from tomatoes, but the evidence is mixed," she says. Furthermore, she says quality control issues—such as contamination with heavy metals—is an ongoing challenge for some supplement makers. 

It's possible that supplements may turn out to provide a benefit for people with prostate cancer, but right now it's hard to say conclusively what is or isn't worth trying. 

Complementary, Not Alternative

Experts who have studied complementary therapies for prostate cancer say these are an important part of providing patients with complete and integrative care. 

"Especially for men diagnosed with earlier stages of prostate cancer that don't yet require treatment, various lifestyle modifications are associated with beneficial outcomes, including, in some studies, lower risk of death from prostate cancer," Ryan says. 

However, he stresses the importance of telling patients that these sorts of interventions should only be used in addition to formal medical interventions—not in place of them. "There's no data to suggest that lifestyle modification is a replacement for standard treatment for this cancer," Ryan says. "These are not going to take the place of having surgery to have the prostate removed, for example."

Fortunately, most patients with prostate cancer aren't looking to swap out conventional medicine for CAM therapies. "Most people just want to cover all the bases," Balneaves says. "We've found that only 3% to 5% ever consider withdrawing or refusing conventional therapies, so most patients are just trying to enhance the conventional cancer treatments they're receiving."

Read More: How to Cope With the Financial Toll of Cancer

While she's supportive of these efforts, she also warns that some patients may overemphasize lifestyle changes in an effort to get better. "I see some people almost take the joy out of life because they feel everything must be strictly managed," she says. 

"I tell people to eat a healthy diet, move every day, and try to maintain or lose weight," she adds. "Engaging in some form of mindfulness training or yoga—things that allow you to remain centered in self—is also helpful." 

The big takeaway is that an integrative approach to care—one that involves both traditional and complementary forms of therapy—is likely to provide the best outcomes. 

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