Treating Prostate Cancer: Options to Consider

Shahmir H. Ali ABD, and Nicholas J. Jury, PhD

The American Cancer Society estimates that there will be more than a quarter of a million new cases of prostate cancer among American men in 2022.1 One out of every 8 men in the U.S. is expected to be diagnosed with prostate cancer during their lifetime, but fortunately most prostate cancers are not aggressive and most men will survive the disease even if it is not treated. Men who are diagnosed with prostate cancer are faced with the difficult decision of deciding what to do next, since treatment is not always necessary, and each treatment option has advantages and disadvantages. The more that patients understand about the options, the more likely that they will make the decision that is right for them. That is the goal of this article.

Types of treatment options: surgery, radiation, surveillance

Although treatment for prostate cancer is rarely urgent and often can be delayed safely, immediate treatment is an option. Surgery or radiation therapy are two of the most common types of prostate cancer treatments. Although there are several types of surgery available to treat early-stage prostate cancer, a radical (open) prostatectomy and a laparoscopic prostatectomy are the most common.2 The aim of these surgeries is to simply remove the prostate itself to prevent the cancer from spreading.

  • Radical (open) prostatectomy: The surgeon removes the prostate and some surrounding tissue by making a cut either in the abdomen or perineum.
  • Laparoscopic prostatectomy: The surgeon makes several small cuts in the abdomen and uses a camera and instruments to remove the prostate and some surrounding issue.

Radiation therapy is an option instead of surgery.  Radiation works by applying high-energy rays to the prostate in order to kill the cancer cells. This is similar to radiation therapy used for other types of cancers. The American Cancer Society lists either surgery or radiation therapy as standard treatment options for prostate cancer.3

Hormone therapy is another option for immediate treatment and is often recommended when the cancer has spread too much for surgery or radiation to be effective. Prostate cells rely on the hormone testosterone to grow, so hormone therapy involves receiving medication to stop testosterone from being produced or reaching the prostate in order to slow the growth of prostate cancer cells.

Finally, since prostate cancer is usually not deadly, it may not require any treatment. Active monitoring (also called active surveillance) has become an increasingly popular “treatment” for prostate cancer patients, particularly those with low or median risk prostate cancer.  Active monitoring consists of visiting a doctor on a regular basis for a PSA or DRE test (for more information on these tests, read our article linked here). In a 2012 analysis of 23 studies, at most one-third of patients choosing active surveillance received additional treatment after being followed up for a median of 6.8 years.4

What is the most effective treatment option?

The question on every prostate cancer patient’s mind is: which type of treatment is best in reducing my risk of death or illness from prostate cancer? Let’s start by discussing surgery. In 2012, a study by researchers at the Department of Veterans Affairs was published in the New England Journal of Medicine, examining the effectiveness of surgery in men with early-stage prostate cancer.5 Known as the Prostate Cancer Intervention versus Observation Trial, or PIVOT, the study compared surgical removal of the prostate with no prostate cancer treatment. The 731 men, with an average age of 67, were randomly assigned to one of the two groups and followed for 8 to 15 years. The findings suggest that on average, prostate cancer surgery does not save the lives of men with early-stage prostate cancer. Almost 6% of those had their prostate removed died, compared to 8% who did not undergo surgery. The survival difference between the patients undergoing surgery and those who did not undergo surgery was not statistically significant, which means that the smaller number who died in the surgery group could have been due to chance.

However, the same study showed that surgery was beneficial for men with a PSA of 10 or higher and men with riskier tumors.5 Surgery reduced the absolute risk of dying from any cause by 13% among men with a PSA of 10 or higher. However, for men with high-risk tumors (such as a PSA above 20 or stage T2c tumor), the 7% lower absolute risk of dying was not statistically significant, probably because relatively more died despite treatment. The lack of statistical significance means it could have happened by chance.

In 2020, a follow-up analysis was published of the PIVOT study. In this analysis, participants of the original study were followed for an additional 7 years.6 The surgery group lived an average of one year longer than the non-surgery group (13.6 versus 12.6 years).  Surgery was especially likely to reduce the risk of dying among young and healthier men. However, more than 90% of the patients died from causes other than prostate cancer, regardless of whether they had undergone surgery.

It is important to emphasize that the PIVOT study only analyzed people who underwent a radical (open) prostatectomy as a surgery and was not able to compare it with other types of surgery (such as laparoscopic prostatectomy).5  However, a 2019 review of all studies comparing the benefits and side effects of radical versus laparoscopic prostatectomy found only 2 studies, both of which reported a lower rate of erectile dysfunction and urinary incontinence than laparoscopic prostatectomy.7 Neither compared rates of survival or recurrence, however.

What about radiation therapy?  In 2015, a study from Australia was published that analyzed 675 patients with intermediate or high-risk prostate cancer that received modern external-beam radiotherapy.8 After 5 years of treatment, 96% of men with intermediate-risk prostate cancer were still alive, as were 91% of those with high-risk prostate cancer. In fact, 99% of men in the study did not die of prostate cancer during those 5 years. However, this study had no comparison group of patients who underwent surgery, other types of radiation, hormonal treatment, or no treatment, so it couldn’t show how beneficial the external-beam radiotherapy was at improving chances of living longer.

Different types of radiation techniques have been compared in research studies. For example, a 2019 study published in the prestigious Journal of the American Medical Association found that, similar to external-beam radiotherapy, men who received stereotactic body therapy (which involves higher doses of radiation across just 4-5 days rather than the 45 days involved with external beam radiotherapy) had a low recurrence of prostate cancer in the approximately 7 years that they were studied after their treatment.9 While stereotactic body therapy can be more cost effective and less burdensome for patients (requiring less time for treatment), the researchers did not analyze whether or not it helped patients live longer than external-beam radiotherapy or other treatments.10

Rather than been used as the only treatment, hormone therapy is commonly used just before, during, or after surgery and radiotherapy.11 For example, doctors may recommend hormone therapy if PSA levels remain high after other types of treatment, or to make other types of treatment more effective (particularly radiation therapy).12  As a result, hormone therapy by itself can’t be directly compared to surgery by itself or radiotherapy by itself. However, in a review of 21 studies involving a total of more than 11,000 patients, patients who underwent hormone therapy prior to radiotherapy were more likely to report progression-free survival from prostate cancer during the next 6 years; hormone therapy after prostatectomy surgery did not improve overall survival.11 However, a study of more than 13,000 prostate cancer patients published in 2022 found that patients who underwent hormone therapy were more than twice as likely to die of heart disease than those who didn’t.13

Which is better?

If you choose to get immediate treatment for prostate cancer, is surgery or radiation therapy or hormonal therapy the better option? The most reliable information often comes from comparing the results of several well-designed studies. A 2017 analysis of several long-term prostate cancer studies revealed mixed findings on the impact of surgery on survival, depending on the comparison group and when the study was conducted.14 For example, the Scandinavian Prostate Cancer Group Study showed that the benefits of surgery increased over time compared to watchful waiting, 15 which suggests that watchful waiting is a reasonable alternative for some years but is a less safe option for a longer period of time.  The Prostate Testing for Cancer and Treatment study found no difference in deaths from prostate cancer or other causes for patients randomized to surgery compared to radiation therapy.16 However, it can be difficult to interpret findings from past research because the types of surgeries has changed over the years. For example, authors note that laparoscopic prostatectomy is now more common than radical (open) prostectomy.14

In 2022, a landmark study of more than 24,000 high-risk prostate cancer patients was published; 40% underwent radical prostatectomy while 60% underwent external beam radiotherapy.17 After 5 years, 4% of those who had surgery had died of prostate cancer, compared to 6% of those who underwent external beam therapy. To minimize bias in the study, the authors also controlled for the effects of age, PSA-levels, and death from other causes during the analysis. These findings suggest that among those with high-risk prostate cancer, surgery holds a slight advantage to radiotherapy in reducing the risk of death from prostate cancer, but they did not compare the chances of dying from any cause.

Now, let’s focus on the alternative to immediate treatment – active monitoring.  In 2015, a long-term analysis of 993 men with favorable or intermediate risk prostate cancer who chose active surveillance found that most patients remained on surveillance and did not receive additional treatment during the 15 years they were followed.18  For example, 76% remained on surveillance after 5 years, and 55% remained after 15 years. During the 15 years of the study, only 1.5% of the patients died of prostate cancer, a mortality rate that authors noted is about the same as patients with favorable-risk prostate cancer that choose immediate surgery or radiotherapy.18 This research tells us that getting treated immediately may not be the best option for many patients with prostate cancer, especially considering the side effects of surgery, radiotherapy, hormonal therapy, and HICU.

Similarly, a 10-year study published in 2016 revealed that neither surgery nor radiation treatments may actually save lives, compared to active monitoring.17 The study randomly assigned 1643 men diagnosed with prostate cancer to one of three groups: surgery, radiation, and active monitoring, between 1999 and 2009.  Unlike the PIVOT study, patients in the active monitoring group underwent tests to determine if their prostate cancer had progressed; these were conducted every 3 months for the first year, and every 6 to 12 months after that. The patients had an average (median) of 10 years of follow-up.  During the 10 years, 169 men died, and there was no significant difference due to treatment assignment. Equally important, only 17 of those 169 deaths were from prostate cancer: 5 in the surgery group, 4 in the radiotherapy group, and 8 in the active-monitoring group. However, prostate cancer was more likely to progress or spread in the group of men who were monitored rather than treated, so that might possibly have implications for small differences in survival if the patients were followed for more than 10 years.

Complications of surgery and radiation

The next question we need to ask is whether the benefits of immediate treatment for prostate cancer outweigh the risks of complications. Surgery and radiotherapy have similar risks and side effects, which can have a devastating short-term and long-term impact on quality of life. The most common complications include:

  • Erectile dysfunction: This is a common and often long-term side effect, particularly from surgery. In a 2016 analysis of multiple prostate cancer studies, 78-87% of those who underwent radical proctectomy reported erectile dysfunction.19 In the short-term, men who underwent radiotherapy are less likely to report erectile dysfunction than men who underwent surgery (61% vs. 79% after 2 years), the difference is smaller and therefore not statistically significant in the long-term (94% vs. 87% after 15 years).20 While oral medications (such as Viagra or Cialis) can help some men experiencing erectile dysfunction after treatment, symptoms may persist for others.21
  • Urinary incontinence: Many men also experience loss in bladder control after treatment. Approximately 23% of men who underwent surgery and 12% who underwent radiotherapy have reported urinary incontinence after treatment.22 Even 15 years of treatment, 18% of men who underwent surgery and 9% who underwent radiotherapy report urinary continence.20 Treatments include medications and physical therapy.
  • Encopresis: Encopresis (reduced control of bowel movements) is also experienced by many men after treatment. However, encopresis is more common after radiotherapy than after surgery after 2 years (34% vs. 14% reporting bowel urgency) although differences are not statistically significant after 15 years (36% vs. 22%).20 While laser therapy and anti-diarrheal agents can help with symptoms of encopresis, few men are completely cured (particularly if encopresis developed after radiotherapy).23

While these represent the most common side effects of prostate cancer treatments, it’s important to remember that new research provides new information almost every year. For example, a study published in 2022 of more than 143,000 prostate cancer patients found that those who underwent radiotherapy were more likely to develop a secondary cancer within 5 years of treatment and also within 15 years of treatment, compared to those who underwent  surgery or active surveillance.24

Sonablate and HIFU: a new type of treatment?

Are there any other options for besides surgery and radiotherapy? One example is Sonablate, which a non-invasive medical device which uses a high-intensity focused ultrasound (HIFU) to destroy cancerous tissue in the prostate. The technology was approved by the Food and Drug Administration (FDA) in 2015, but it was approved for “prostate tissue ablation,” not for treating prostate cancer.25 This FDA approval decision was based on the fact that Sonablate had not been proven to reduce deaths from prostate cancer, with the hope that destroying cancerous tissue could eventually be proven to reduce deaths.

A 2020 analysis of 16 studies involving more than 5,000 patients reported that patients using HIFU therapies experienced many of the same side effects as surgery and radiotherapy patients.26  However the rates varied so dramatically among the study results that it is impossible to compare HIFU to the other treatments: for example, 13-90% of those receiving HIFU reported erectile dysfunction approximately 6-12 months after treatment, while 4-34% reported urinary incontinence approximately 2-4 years after treatment.  Moreover, while most patients who undergo HIFU are still alive 2 years 27 and 5 years 28 after treatment, 7 years after Sonablate’s approval there is still no research directly comparing HIFU with radiotherapy or surgery in terms of the major side effects or any conclusive evidence on whether it is as effective, more effective, or less effective in improving overall survival or progression-free survival.

Bottom Line

Deciding on a treatment option can be a difficult decision for prostate cancer patients. After learning about the risk level of their particular cancer, patients have to decide whether they should get immediate treatment, or if active surveillance might be the better option. One issue is the age of the patient and their other medical problems; why risk the side effects if a patient has numerous other serious medical problems that will limit the number of years they are likely to live?  In addition to considering age and general health, doctors at Johns Hopkins Medicine recommend that if a patient is not experiencing any symptoms, the cancerous tumor is small and expected to grow slowly, and the cancer is confined to the prostate, then active surveillance might be the better option.29 On the other hand, high-risk prostate cancer patients may require immediate treatment. In this case, it is important to consult with your team of doctors (oncologists, surgeons, and radiologists) on whether surgery, radiotherapy, hormonal therapy, or active monitoring may be more appropriate given the circumstances of the cancer and your current of health.

 

References

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