Movember; Bladder Cancer is also a Key Issue in Men’s Health

At the clinic we are into a third week of Movember. My own moustache (now a full beard; more out of laziness than anything) is becoming increasingly less irritating. It is now beginning to make decisions for itself which is very worrying. There is even term for fear of beards is which pogonophobia…such a great word! In times long gone the beard, it was once argued, prevented toothache by capturing and warming the air around the mouth. In addition, a beard was said to keep the throat warm, which in turn prevented respiratory ailments and protected the voice. Whether I have mine long enough to test these fine concepts remains to be seen. I console myself that there is only another week to go before I have a wet shave. All for a worthy cause which is of course men’s health. This was also prompted by two patients who were recently diagnosed with prostate cancer.

Men are 2-3 Times More Likely to Suffer from Bladder Cancer

Hitherto I have written two articles on this men’s health, one on prostate cancer and another on why men are more likely to suffer from heart attacks;  but this is not the only issue that us men are susceptible to.  Few people realise that men are also three to four times more likely to develop bladder cancer than women. Like prostate cancer most diagnoses are made after the age of 55 with the average age at diagnosis of 73. In England, about 18,000 people a year are diagnosed with bladder cancer and roughly 4,500 die of it (or 25%). In the US meanwhile in 2017 there were an estimated 60,500 men diagnosed with bladder cancer and 12,240 deaths. In the same year there were 18,540 women diagnosed in total with an estimated 4,630 deaths. The overall five-year survival rate for bladder cancer is 77%.

Smoking and Bladder Cancer

As with many cancers the single biggest risk factor is smoking, which increases your risk for bladder cancer by three times. The American Cancer Society says smoking causes about 50% of bladder cancers. Smokers quickly come to crave the reward of nicotine, requiring increasing amounts as the body becomes habituated, and face powerful withdrawal symptoms when quitting. Unfortunately, nitrosamines are also present in cigarette tobacco as nicotine-derived compounds. These compounds form within the body when we smoke, two of these compounds are nicotine-derived nitrosaminoketone (NNK) and N-Nitrosonornicotine (NNN). Both are highly reactive compounds and parts of their structures can be transferred to our DNA base. This means that genetic information can then be misread when our DNA is replicated. NNK for instance has two side chains (a methyl and a ketone group) that can be transferred to DNA. The methyl side chain is very evasive because it is small enough to evade any self-repair mechanisms that we might have, but different enough to corrupt the pairing of the bases in our DNA! In tobacco smoke there are also dozens of other carcinogenic compounds that modify and mutate DNA in other ways. Cigarette smoke constantly attacks the DNA in cells, making changes randomly in multiple genes. In one out of five smokers, these mutations will build up over the years and ultimately corrupt just the right combination of genes, creating a cancer cell.

Ethnic Origin as a Risk Factor

Most of the time, bladder cancer begins in the inner wall of the lining of the bladder (urothelium or transitional epithelium). Untreated, it can spread into nearby tissues and lymph nodes. Unlike  prostate cancer where men of African descent are most at risk, with bladder cancer Caucasian men have the greatest risk factor. Caucasians are twice as likely as people of African or Hispanic origin to get bladder cancer. Oddly women of African descent are at particularly high risk for getting a late onset bladder cancer. But clearly each person’s relative risk also depends on other factors such as environment, medication, genetics and family history. These risk factors will be a mixture of either inherited or acquired as with prostate cancer. About half of the time, bladder cancer is diagnosed before it spreads beyond the inner layer of the bladder wall. 30% of  bladder cancers have typically invaded deeper by time they are diagnosed, but not beyond the bladder. 4% of the time, it’s not diagnosed until it has spread to a distant site. Other cases are usually discovered at a later stage, when the cancer has spread to nearby lymph nodes or tissue.

Symptoms of Bladder Cancer

Despite differences in anatomy, the symptoms of bladder cancer for both sexes are similar. Signs may be very mild at first, making them easy to dismiss, but they include: frequent and painful urination, lower back or pelvic pain and blood in the urine. It is worth pointing out that these symptoms are also often more likely caused by a urinary tract infection or, for men, an enlarged prostate. One of the obvious questions to ask is why are we men specifically more likely to get bladder cancer in the first instance?

Why is it more Prevalent in Men?

At least one of the reasons why bladder cancer is so much more prevalent in men is because of a specific molecular receptor or protein. This androgen receptor is much more active in men than women and it plays an important role in the development of the disease. This receptor is central to the action of testosterone and other hormones that are much more plentiful in men than women. There are several studies that have investigated this idea. One key study used poor little mice (I am afraid so!) who had these receptors sites disabled (this was done in a humane way!). Not a single mouse with disabled androgen receptors developed bladder cancer. Results were unequivocal.  Those mice without this receptor had dramatically lower rates of bladder cancer compared to normal mice with the receptor, and equally human cancer cells with the receptor were much more aggressive than those without it. Mice develop bladder cancer for many of the same reasons people do, and the molecular signals that control cancer development in mice mirror those in us. That’s why it is a good idea to use them as models by the way.

What are the Outcomes?

Interestingly this same androgen receptor also plays a role in prostate cancer. Therefore, hormone therapy is often used to block the supply of hormones that turn on this receptor. This is a staple of treatment for men with advanced disease. According to Cancer Research UK  49% of patients diagnosed with bladder cancer have surgery to remove the tumour as part of their primary cancer treatment, 21% have radiotherapy, 34% of patients have chemotherapy.  Most bladder cancers are diagnosed when they are still only in the bladder lining. The outlook for early bladder cancers depends on several factors, such as exactly how far the cancer cells have gone into the bladder lining, the number of tumours, tumour width. One of the key issues is also what the cancer cells look like under a microscope. In general, these studies will determine the grade of cancer cells. A lower grade indicates a slower-growing cancer and a higher grade indicates a faster-growing one. Generally, if caught early outcomes are typically good.