What Is Metastatic Castration-Resistant Prostate Cancer (mCRPC)?

Metastatic castration-resistant prostate cancer (mCRPC) and its precursor, metastatic hormone sensitive prostate cancer (mHSPC), are advanced forms of the condition that don’t respond to initial treatments, such as surgery and hormone therapy, and have started to spread beyond the prostate.

Both mCRPC and mHSPC differ from non-metastatic castration-sensitive cancer (nmCSPC), in which the disease is responds to standard hormone treatment called androgen deprivation therapy (ADT). Specifically, mCRPC is particularly dangerous and leads to a very poor prognosis.

The prostate is part of the male reproductive system that surrounds the urethra. The prostate gland produces some of the fluid that carries and protects sperm after ejaculation. Overall, prostate cancer is the second most common cancer in men, with 191,930 new cases—and 33,330 deaths—estimated for 2020.

Types of Castration-Resistant Prostate Cancer

Castration-resistant prostate cancers are a class of cancer that do not respond to first-line treatments, which include surgery and/or a standard hormone treatment called androgen-deprivation therapy (ADT). While treatments for mCRPC can be highly effective, especially if the disease is caught early, it is generally incurable. Given that they’re resistant to some therapies, mHSPC and mCRPC represent particularly challenging cases for patients and medical professionals alike.

ADT works by lowering testosterone levels in the body, which can be achieved by either removing the testicles or employing drugs like Lupron, which lower the production of testosterone. In many prostate cancer cases, this treatment can successfully delay or stop tumor growth.

Whereas mCRPC and mHSPC refer to cases where the cancer calls have started to spread (also known as “metastasis”), nmCSPC is an earlier form that’s confined to the prostate. The difference between the former two of the three conditions is also a matter of progression, with mCRPC being the more advanced and widespread form of the cancer.

Here’s a quick breakdown of these related conditions:

Metastatic Hormone Sensitive Prostate Cancer (mHSPC)

This form of prostate cancer can be an initial diagnosis but more often refers to cases where surgeries or other initial treatments to remove tumors from the prostate haven’t succeeded in stopping its progression.

Notably, too, these cases are defined by metastasis, meaning it has started to spread to other structures in the body, such as bones or the lymph nodes. However, the development of castration resistance is part of the eventual and expected progression of the disease—even while on ADT.

Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Basically, mCRPC can be defined as mHSPC that has spread and progressed further, though the exact mechanism of how one leads to the other is not fully understood.

Notably, this type is characterized by the persistence of the disease following ADT, with cancer cells spreading to bone, lymph nodes, and other organs despite the lack of androgen. It’s a more severe, advanced form of cancer and yields a poorer prognosis.

Symptoms of mCRPC/mHSPC    

What’s challenging about some prostate cases is that there’s a chance they can be asymptomatic, especially in their earlier phases. When it comes to mCRPC and mHSPC, symptoms will arise not only in and around the prostate but in those other body systems to which the cancer has spread. These include:

  • Frequent urination
  • Nocturia (frequent need to urinate at night)
  • Difficulty during urination
  • Hematuria (blood in the urine)
  • Painful urination
  • Inability to maintain erection
  • Painful ejaculation

If the cancer has started to spread, it can affect other bodily systems, leading to:

  • Severe bone pain (primarily pelvis, vertebrae, hips, femur, or ribs)
  • Tingling sensations in the legs or lower back
  • Leg weakness
  • Paralysis
  • Urinary/fecal incontinence

If you’ve been diagnosed with prostate cancer, or are experiencing any of these symptoms, seek out medical attention immediately.

Causes

Generally speaking, mCRPC and mHSPC arise as cancer cells start to develop and divide in the prostate and continue to spread despite therapy. Doctors still don’t fully understand the exact mechanism that causes this disease to arise; however, they have been able to localize a range of risk factors and associated conditions. Here’s a quick breakdown:

  • Sex: The prostate only exists in males, so females are not at risk.
  • Age: Older age is a strong predictor of prostate cancer formation, though seniors typically develop less malignant forms of this disease.
  • Increased height: Males that are taller are more likely to develop prostate cancer.
  • Obesity: Among the health effects of being clinically obese is a higher risk of this condition.
  • High blood pressure (hypertension): A history of hypertension also increases the chances of developing prostate cancer.
  • Genetics: As with all cancers, there’s a strong genetic component to mCRPC and mHSPC. Men with a father or brother who has developed prostate cancer have a doubled risk of developing this disease. 
  • Diet: Put broadly, the typical Western diet has been linked with this disease. Advanced prostate cancer risk increases with elevated calcium intake, foods high in saturated fats, dairy consumption, and insufficient amounts of vitamin D. Some studies have linked red meat consumption with this condition, while others noted a vegetarian diet reduces risk. Despite some evidence, more research is needed to confirm these associations.
  • Lack of exercise: Likely because this also contributes to obesity and hypertension, lack of exercise has been linked with prostate cancer development.
  • Elevated testosterone levels: Higher levels of testosterone (androgen) also increases the chances of developing this disease.
  • Race/ethnicity: Incidence of prostate cancer is higher in Black men when compared to white and Hispanic populations. Notably, mortality is also significantly higher among this demographic group.
  • Exposure to chemicals: Incidence of advanced prostate cancers have been seen among those who’ve been exposed to the toxic chemical, Agent Orange.
  • Prior infections: Those who have or have had chlamydia, gonorrhea, or syphilis have higher rates of developing this cancer. There is some evidence that human papillomavirus (HPV) is linked as well.

Diagnosis

Generally speaking, prostate cancers are graded on a scale that goes from a score of 1, meaning least likely to metastasize to a score of 5, the most severe from. The aim of diagnosis, then, is to assess not only the presence of cancer, but to assess whether it’s spreading, and if so, where it’s spreading to. This is typically done using several methods, including physical examination, blood tests, imaging, and core needle biopsy.

Physical Examination

The first step of diagnosis involves a careful review of medical history as well as physical examination of the patient. This entails an assessment of any reported symptoms alongside an evaluation of relevant risk factors.

In addition, the doctor will perform a digital rectal examination (DRE), where they insert a gloved, lubricated finger into the rectum to physically feel for the presence of any tumors. If a potential problem is detected, they’ll order blood testing. 

Prostate-Specific Antigen (PSA)

The primary blood work done if prostate cancer is suspected is the PSA blood test. This tests for the presence of a specific protein called the prostate-specific antigen. While all men have some PSA, higher levels may indicate the presence of cancer.

The PSA blood test is not definitive, but it can help doctors rule out cases where cancer is unlikely. Elevated levels will indicate the need for further tests.

Core Needle Biopsy

To confirm the diagnosis, a specialized doctor—usually a urologist—will need to perform a core needle biopsy. This involves taking samples of prostate tissue and evaluating them for the presence of cancer cells.

In the procedure, a specialized needle is inserted either through the rectum or the skin between the scrotum and anus. The samples are then evaluated by a pathologist.

Imaging

During biopsy and afterward, doctors will rely on imaging approaches, such as transrectal ultrasound, magnetic resonance imaging (MRI), computerized tomography (CT/CAT scan), X-ray, or positron emission tomography (PET scan) to assess the full extent of cancer spread and tumor growth.

The specific approach used is based on the location of the issues; for instance, transrectal ultrasound will focus on the prostate area, while CAT scan is typically best to assess if the cancer has spread to lymph nodes. Since prostate cancer easily spreads to bones, a specialized bone scan X-ray will be needed to fully assess the spread.

Treatment

As highlighted, the tricky thing about mCRPC and mHSPC is that they are, by definition, more aggressive and resistant to initial treatments. That said, there are an increasing number of treatment approaches, improving outcomes for cancer patients. Specific treatment regimens will vary based on individual cases and may include:

  • Docefrez/Taxotere (docetaxel): The most frequently prescribed chemotherapy drug to treat mCRPC and mHSPC is the drug Docefrez (docetaxel). This medication functions by targeting microtubules (tubes in cells that help move nutrients and cellular structures) on cancer cells, inhibiting their ability to divide and spread.
  • Jevtana (cabazitaxel): Jeytana is another chemotherapy drug that, like Docefrez, binds to microtubules in cells to prevent their functioning and reproduction. 
  • Zytiga (abiraterone acetate): Zytiga is a drug that blocks a specific enzyme, cytochrome P (CYP) 17, that’s essential to the synthesis of androgen. Since the presence of androgen boosts cancer growth and activity, this can help prevent the disease from getting worse or spreading.
  • Enzalutamide: Where Zytiga prevents the development of androgen, Enzalutamide is a drug that targets and blocks receptors of this hormone. In effect, this lowers androgen levels and thereby helps rein in cancer.
  • Radium-223: For cases where the cancer has spread into the bone, radiation treatment with radium-223 may be indicated. Used either alone or in combination with chemotherapy, this therapy yields fewer side-effects than some other forms of radiotherapy.
  • Provenge (sipuleucel-T): Approved for use on asymptomatic or minimally-symptomatic cases of mCRPC, sipuleucel-T is a drug that activates the immune system to target cancer cells.
  • Olaparib: Though primarily indicated for breast, ovarian, and fallopian cancers in women, Olaparib works by inhibiting poly(ADP–ribose) polymerase (PARP), an enzyme associated with cellular repair that becomes overactive in tumor formation. Currently, this drug has been designated “breakthrough designation” by the Food and Drug Administration (FDA), meaning it’s on a faster track to be approved for use on mCRPC and mHSPC. It's currently being evaluated in patients with certain genetic mutations in their tumors, such as a BRCA2 mutation.
  • Keytruda (pembrolizumab): This drug is part of a class called “check-point inhibitors,” which function by trying to increase the activity of the body's own immune system to fight the cancer. While there’s evidence that this class of drug can work against castration-resistant prostate cancers, more research is necessary to more fully establish its efficacy.

As with many cancer cases, more than one treatment approach may be necessary to yield therapeutic results.

Prognosis

Unfortunately, since mHSPC and mCRPC are more aggressive cancers, and since there’s no definitive cure, prognosis is relatively poor. That said, thanks to newly devised therapies and treatments, the numbers are improving.

Keep in mind that the numbers presented here are averages, and there can be a great deal of variation. Among the important measures when discussing cancer is survival rate at five years.

While the outlook for prostate cancers that have not spread is quite positive—if caught in time and treated, the majority of these patients are expected to be alive in five years. For those that have metastasized cancers, like mHSPC and mCRPC, the number is significantly lower—about 31%.

The most challenging question, of course, is the most important one: How long do patients have? There are many factors at play here, and probably the most crucial is timing. The sooner this cancer is discovered, the better the chances of a positive outcome.

Following a diagnosis of mCRPC, the expected prognosis has been found to be pretty grim—with a median of 11 to 24 months.

Encouragingly, newer therapies have improved the outlook. As these have hit the market, researchers have already started seeing significant changes. 

Coping

There’s no doubt that a cancer diagnosis can be incredibly upsetting and unsettling. At the end of the day, mHSPC and mCRPC represent advanced stages of a deadly disease, and there’s no doubt that treatment can be disruptive and difficult.

For patients, it’s absolutely essential to have a support system in place; though it can be very challenging, it’s helpful to talk to your family about what’s happening. Alongside close friends, they’ll be an essential source of help and support. The better you’re able to communicate, the easier everything will be.

Outside of friends and family, though, you may find the need to seek out professional counseling or a support group to help you cope. Psychiatrists and other mental health professionals can certainly help in this difficult time, so you may find it helpful to ask your oncologist about any services or experts they know.

In addition, there are many support groups and services for those with cancer. Alongside providing clinical information, organizations such as the Cancer Survivor’s Network or the Urology Care Foundation help foster an enriching and supportive community of and for those suffering. The burden of this condition is intense; there’s no reason you should go it alone.

A Word from Verywell

There’s no way around the fact that a cancer diagnosis is a massive, life-altering event. On top of that, most treatment approaches can be themselves very difficult and draining on both physical and emotional levels.

As hard as it all can be, it’s important not to lose hope. While prognosis for mHSPC and mCRPC is relatively poor, it’s important to remember that it has been steadily improving as new therapies and approaches have been developed.

Today, people with metastatic prostate cancer, put simply, are in a much better position than they’ve ever been before. With the right care, and the support of loved ones, you can put yourself in a good position to combat this cancer.     

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