The Conundrums of Prostate Cancer

Cancer of the prostate gland is extremely common – so common, in fact, that in some form it will affect most men if they live long enough.  It is the second-most diagnosed cancer in American men, behind non-melanoma skin cancers.  Many prostate cancers grow slowly, are confined to the gland itself, do not cause serious symptoms, and do not require intensive, if any, treatment. Others, however, are aggressive and can spread quickly.

Given such variability, the significant side effects of some treatments, and the dread that many people experience with a cancer diagnosis, deciding what to do about prostate cancer can be vexing for both doctors and patients.

There are two common ways to screen for cancer in the prostate, a small walnut-shaped gland in males that produces the seminal fluid that transports sperm.  The first is a digital rectal exam, which is performed by a doctor inserting a gloved finger into the rectum to feel for hard or lumpy areas of the gland.  The second is a blood test to measure prostate-specific antigen (PSA), a protein produced by the prostate gland. Elevated PSA levels indicate a greater likelihood of cancer.

Screening can reduce prostate cancer mortality by detecting cancers early, but – and here’s the vexing part -- it can come at the expense of overdiagnosis and overtreatment of cancers that, if left untreated, will not shorten the patient’s lifespan.

Once prostate cancer has been discovered and confirmed, usually by means of a biopsy, a number of options are available, but the most important decision to be made is whether to treat or not.  Foregoing treatment is a viable option if the cancer is small, asymptomatic, slow growing, localized (hasn’t spread), and is not causing a highly elevated PSA.  

There are two common alternatives to treatment. The first, “active monitoring” (sometimes called active surveillance), involves following the cancer closely, which usually requires a physician visit with a PSA blood test about every six months and a digital rectal exam at least annually.  In addition, prostate biopsies and imaging tests may be done periodically.  The second, “watchful waiting,” is a less intensive type of follow-up that relies more on changes in a patient’s symptoms than frequent testing to decide whether treatment is needed.  

Either of those while deferring treatment avoids the side effects of surgery, drugs, and radiation and is most appropriate when the risk of the cancer progressing is very low. Because prostate cancer grows very slowly, some very small cancers may never cause signs and symptoms, and many men who choose to forego treatment experience their normal life spans before the cancer ever grows large enough to require intervention.

This subject became a hot topic recently with the publication on March 11^th of the results of a long-running U.K. clinical trial that followed more than 1,600 men diagnosed with localized prostate cancer between 1999 and 2009.  The patients were initially randomly assigned to one of three groups: active monitoring; radiotherapy (which used hormone-blockers and radiation to shrink tumors); or prostatectomy – that is, surgery to remove the prostate.  Those who were assigned to monitoring could change groups during the study if their cancers progressed so that more aggressive treatment became appropriate.

The salient findings:

• At a median follow-up of 15 years (range, 11 to 21), 45 patients, or about 3% of the participants, had died of prostate cancer.
• There were no significant differences in the number of prostate cancer deaths among the three groups.
• Patients in the active monitoring group were more likely to experience progression of their cancer and more likely to have it spread, compared with the other groups.
•  About 9% of patients in the active monitoring group had metastasis of their cancer, compared with 5% in the two other groups.
• Patients in the active monitoring group had a much lower incidence of life-altering complications such as incontinence and erectile dysfunction that can follow aggressive treatment for prostate cancer, but they were no more likely to die of their cancers than men who had surgery to remove their prostate or who were treated with hormone blockers and radiation.

The authors’ conclusions: “After 15 years of follow-up, prostate cancer–specific mortality was low regardless of the treatment assigned. Thus, the choice of therapy involves weighing trade-offs between benefits and harms associated with treatments for localized prostate cancer.” 

For patients who opt for treatment at whatever stage their cancer is, there are various options, described briefly below and in more detail here.

Treatment modalities:  

• Surgery -- a common choice, which usually involves removing the entire prostate gland, if the cancer is not thought to have spread outside the gland.
• Radiation -- uses high-energy rays or particles to kill cancer cells. Can be used as an initial treatment or to treat recurrence or metastases.  Different technologies and equipment are available, depending on the stage of the cancer and other factors.
• Cryotherapy -- uses ultra-cold temperatures to freeze and kill prostate cancer cells and most of the prostate.
• Hormonal therapy – suppresses levels in the body of male hormones, called androgens, which spur the growth of prostate cancer cells.
• Chemotherapy – “chemo,” via IV infusion or oral medications, may be used if the cancer has spread outside the prostate gland and if hormone therapy isn’t working. Can also be given in conjunction with hormone therapy.
• Immunotherapy – stimulates the patient’s immune system to kill the cancer cells, using several distinct modalities, including vaccines and drugs called immune checkpoint inhibitors.
• “Targeted” therapy – uses drugs focused on certain targets in the cancer cells that makes them different from normal, healthy cells. The targets vary, but the drugs all interfere in some way with how a cancer cell grows, divides, repairs itself, or interacts with other cells.

Because prostate cancer is so common, the various treatment modalities continue to be intensively studied and refined, but all have side effects that, for a given individual, might outweigh the benefits.  For many men, the prospect of impotence or incontinence is daunting or even a deal-breaker.  Therefore, the pivotal decision whether to opt for treatment or for watchful waiting or active monitoring can be excruciatingly difficult.  Dr. Freddie Hamdy, professor of surgery and urology at the University of Oxford and the lead author on the article reporting the results of the large U.K. study, offers sound advice: "The good news is that if you're diagnosed with prostate cancer, don't panic, and take your time to make a decision" about how to proceed.

 As always, the guiding principle should be that the cure should not be worse than the disease, and there is no one-size-fits-all blueprint.