Most cases of prostate cancer are localized, but when it spreads to other parts of the body, it’s known as metastatic prostate cancer.

The main pathway for treating metastatic prostate cancer (mCaP) focuses on starving the disease of testosterone (androgen).

In 1941, medical researchers Huggins and Hodges first showed that removing the testicles or giving estrogen could shrink tumors and improve symptoms. This work led to a Nobel Prize in physiology.

Today, hormone modulation therapy (HMT) or androgen deprivation therapy (ADT) generally involves medication. Injection therapies like degarelix (Firmagon) or leuprolide (Eligard) interrupt the testosterone production signal from the brain to the testicles.

Most patients will receive one of these treatments first.

In many patients, mCaP will eventually become castrate-resistant, meaning standard HMT no longer controls the disease.

Several newer anti-androgen medications such as abiraterone (Zytiga), darolutamide (Nubeqa), apalutamide (Erleada), and enzalutamide (Xtandi) can then be used. It’s important to note that these are not “chemotherapy” medications.

Docetaxel (Taxotere) is a standard chemotherapeutic agent. It’s traditionally used for high-burden metastatic castrate-sensitive disease, meaning cases in which the cancer has metastasized to several locations in the body, including outside the axial skeleton (head and spine), and locations outside of the bones as well, but the disease is still controlled by HMT. It can also be used for castrate-resistant disease in general.

The data now shows that an effective treatment for individuals with metastatic castrate-sensitive prostate cancer (mCSPC) is a first-line therapy approach of a combination of either ADT (using leuprorelin or degarelix) or a bilateral orchiectomy (surgical removal of the testicles), along with HMT (using abiraterone, enzalutamide, apalutamide, or darolutamide).

However, if an individual has mCSPC and there is a high burden of disease, then triplet therapy is suggested, with doxetaxel (Taxotere) chemotherapy medication, and oral darolutamide (Nubeqa) or enzalutamide (Xtandi), plus ADT.

Usually, people with mCaP aren’t offered radiation or prostate removal surgery (since the cancer has spread, and a cure is unlikely). If the patient has a very low burden metastatic disease (cancer that is in the prostate but has spread to one or two sites), then ADT, followed by a prostatectomy to remove all or some of the prostate gland, or radiation, are treatment options that may offer a cure.

Doctors consider several factors when determining the right treatment for each patient.

First, the disease is staged, usually with imaging like a:

  • PET-CT scan
  • CT scan
  • bone scan

Second, the symptomatic status of the patient is assessed. Some people can have significant pain, mobility limitations, or urinary symptoms due to metastases or local spread.

Third, the sensitivity of the disease to HMT (castrate status) is determined. This is usually done by measuring prostate-specific antigen (PSA) and testosterone levels.

Finally, a discussion between the patient and doctor should focus on the goals of care and treatment options available based on the above factors.

It’s important to note that the patient may have comorbidities or medical conditions that could make them ineligible for a particular treatment. These can include neuropathy, a history of coronary heart disease, strokes, heart attacks, or abnormal cardiac rhythms, among others.

The main benefit of treating metastatic prostate cancer is to improve symptoms and prolong life. It’s important to note that, for the most part, metastatic prostate cancer can’t be cured, so the focus is more on disease management.

The side effects of HMT are not insignificant. Symptoms include:

  • hot flashes
  • low energy levels
  • mood swings
  • weight gain
  • depression
  • breast tenderness/growth
  • loss of interest in sex

Doctors must also monitor and treat patients for:

  • loss of bone density
  • cardiovascular disease
  • diabetes

There’s also emerging data on how long-term HMT can affect cognitive function, especially in older adults.

Hot flashes tend to be the most bothersome.

Non-medication strategies like keeping cool drinks with you, dressing comfortably, relaxation techniques, and breathing exercises might be helpful.

Medications and supplements, such as vitamin E, megestrol, estrogen therapies, antidepressants, and neuroleptic agents like gabapentin can improve hot flashes but often come with dose-limiting side effects

Pain, although usually not a side effect of treatment, is managed with non-narcotic or narcotic pain medications. We sometimes have to manage the side effects of pain medication, such as constipation.

Using the mildest medication is always best.

Absolutely! Whenever we can avoid adding a medication but still provide a benefit, we’re doing something right.

Acupuncture has been studied by several groups as a way to alter the vasomotor (blood vessel) response of the body that causes the hot flash. Some studies suggest up to a 40% reduction in symptoms with an acupuncture treatment course of 5 to 12 weeks.

There has been some interest in using soy products, due to estrogen-like substances they contain. But results generally showed no significant improvement.

Multiple additional natural products and herbs have been suggested, but quality research on these is lacking. You should discuss any supplement with your doctor before adding it to your regimen.

The most important thing you can do is to stay physically active and strong. This includes following a heart-healthy diet and exercising.

Cardiovascular exercise is the most important. The degree, or intensity and duration, of cardio exercise depends on the individual person.

Several studies have pointed to a link between obesity and aggressive prostate cancer, although the mechanism is still being worked out.

Weight loss is generally encouraged if you’re overweight, but excessive or unintentional weight loss can be a sign of disease progression and should be discussed with your doctor.

Finally, if you’re a smoker, stop! If you’re finding it hard to quit, ask your doctor about products and medications that might help you.

Clinical trials are designed to answer a wide array of clinical questions. A quick search of shows over 150 mCaP trials currently enrolling patients in the United States.

It’s important to remember that clinical trials are often not intended to treat or cure participants but rather to further the knowledge of the scientific community.

If you’re diagnosed with mCaP and are inclined to get involved with research, discuss it with your physician or check the site above for trials in your area.

I would add that for patients very close to the end of life, time might be better spent with family and friends.

That’s a tough one! The research and progress in treating this disease have come so far in just the past few years.

We still have a lot of work to do.

In my opinion, current research into theranostics, which incorporates targeted drug delivery with advanced imaging techniques, offers particular promise.

I also believe the key to outsmarting the disease is to stay a step ahead. This means identifying and anticipating the progression of the tumor’s escape mechanisms and preempting them.

I cannot stress enough the importance of picking the right treatment for each individual. Side effects and the expectations for disease response should be clearly discussed and understood.

Statistically, about one-third of people with metastatic prostate cancer will live more than 5 years. Understanding where your disease is on that continuum can be important for both treatment and lifestyle decisions.

That said, I am consistently amazed by what we as a medical and scientific community can do together. The huge efforts being applied to prostate cancer research hold significant promise for new and better treatment options in the near future.

Dr. Joseph Brito provides general urologic care with a special focus on minimally invasive surgical techniques and urologic oncology. Brito received his MD from George Washington University School of Medicine and Health Sciences. Brito completed a residency in urology at Rhode Island Hospital and Alpert Medical School of Brown University and trained at Yale School of Medicine in clinical oncology. Brito is a member of the American Urological Association.