Androgen deprivation therapy (ADT) has been a mainstay of treatment in advanced (metastatic) prostate cancer for more than fifty years. In the past decade or so, doctors who treat advanced prostate cancer have come to understand that ADT alone is not enough. As a result, treatment intensification has become common.
Chemotherapy was the first treatment intensification approach to be adopted. Now so-called novel hormonal therapies (NHTs) are the treatment intensification used for most patients. NHTs are also known as androgen receptor-axis-targeted therapies (ARATs).
While ADT effectively decreases the testosterone within the body that drives prostate cancer growth, the success of these treatments clearly shows that targeting testosterone-driven pathways can help treat advanced prostate cancer.
Abiraterone Acetate
The first NHT to have proven benefit was abiraterone acetate. Abiraterone is an “androgen biosynthesis inhibitor.” It acts to block one of the key enzymes in the testicles, adrenal glands, and prostate cancer cells needed to produce testosterone. Because the production pathway of testosterone is shared with other important hormones in the body, patients who receive abiraterone acetate also take a corticosteroid (prednisone, prednisolone, etc.) to prevent a lack of these other hormones.
Who might be prescribed abiraterone acetate?
Abiraterone is approved and has shown survival benefits for men with metastatic castration-sensitive prostate cancer (mCSPC) where abiraterone will be started at the same time or shortly after ADT and in metastatic castration-resistant prostate cancer (mCRPC) in which abiraterone will be started as a result of disease progression while on ADT.
Patients receiving abiraterone for metastatic castration-resistant prostate cancer may or may not have already had chemotherapy.
The LATITUDE and STAMPEDE trials showed that men with mCSPC who received ADT + abiraterone had a 38% and 37%, respectively, decreased risk of death compared to men receiving ADT alone.
Among men with mCRPC that had not already had chemotherapy in the COU-AA-302 trial, men receiving abiraterone had a 25% decreased risk of death compared to men receiving placebo + prednisone. Among men with mCRPC that had already had chemotherapy in the COU-AA-301 trial, men receiving abiraterone had a 35% decreased risk of death compared to men receiving placebo + prednisone.
Patients who should not take abiraterone
There are a few reasons why patients should not take abiraterone. Patients with an allergy or hypersensitivity to abiraterone should not receive it.
Similarly, those with severe liver disease, too many or not enough hormones in the pathway that abiraterone affects (too much mineralocorticoid or not enough adrenocorticoid), severe heart disease, and those with low blood potassium (hypokalemia) should take abiraterone with caution.
Instructions for taking abiraterone
Abiraterone acetate is prescribed at four tablets to be taken each day. It should be taken by mouth on an empty stomach, either one hour before or two hours after eating food, to maximize absorption. Also, as mentioned before, you will be prescribed a corticosteroid to be taken either once or twice daily.
Abiraterone is metabolized (processed) by specific enzymes in the liver. As a result, there may be interactions between abiraterone and medications that block these enzymes or increase their activity.
Medications that may block these liver enzymes include:
- ketoconazole
- itraconazole
- clarithromycin
- atazanavir
- nefazodone
- saquinavir
- telithromycin
- ritonavir
- indinavir
- nelfinavir
- voriconazole
Medications that increase the activity of liver enzymes include:
- phenytoin
- carbamazepine
- rifampin
- rifabutin
- rifapentine
- phenobarbital
As your doctor discusses treatment options for advanced prostate cancer, make sure they are aware of all of the other medications that you are taking. Further, a cancer pharmacist can be very helpful to make sure that there are no harmful interactions between medications.
Side effects of Abiraterone
The most common side effects of abiraterone relate to it stopping the production of testosterone and other related hormones.
Abiraterone side effects include:
- high blood pressure
- low blood potassium (hypokalemia)
- swelling of the hands or legs (peripheral edema)
- urinary tract infections
- diarrhea
- rash
- increases in liver enzymes
Many other side effects are possible and may be related to abiraterone treatment.
As always, the content on this site is not intended to serve as specific medical advice. Discuss the specifics of your clinical situation and your treatment options with your doctor.
Enzalutamide
Enzalutamide emerged shortly after data for abiraterone acetate as the first NHT became available. Unlike abiraterone which acts to block the production of testosterone and its related hormones, enzalutamide blocks the action of testosterone. Enzalutamide does this in many ways:
- By blocking the binding of testosterone to the androgen receptor (the interaction necessary to turn on the receptor)
- By blocking the activation of the androgen receptor that comes following its binding with testosterone (the “on switch” for testosterone’s function)
- By blocking the movement of the androgen receptor into the nucleus of the cell (the inside of the cell) where it exerts its effects on DNA (stopping the movement of testosterone and the receptor to the part of the cell where they carry out their function). In this mechanism, enzalutamide acts as a more potent version of prior anti-androgens such as bicalutamide.
Who might be prescribed Enzalutamide?
Enzalutamide is approved and has shown survival benefits for men with:
- Metastatic castration-sensitive prostate cancer (mCSPC). Enzalutamide will be started at the same time as or shortly after ADT.
- Non-metastatic castration-resistant prostate cancer (nmCRPC). Enzalutamide will be started after the PSA goes up even though the testosterone is low while on ADT and there are no sites of metastasis (cancer spreading) on imaging.
- Metastatic castration-resistant prostate cancer (mCRPC). Enzalutamide will be started as a result of disease progression while on ADT.
Patients who receive enzalutamide for mCRPC may or may not have already had chemotherapy.
Both ENZAMET and ARCHES have provided randomized controlled data demonstrating the benefit of enzalutamide for treating mCSPC disease, even among patients receiving docetaxel, with a 33% and 34% reduction in the risk of death, respectively, compared to men receiving ADT alone.
For patients with nmCRPC, the PROSPER trial was designed to show a decreased chance of developing metastatic disease. Not only did enzalutamide do this (with an impressive 72% decreased risk of metastasis), use of enzalutamide for nmCRPC also decreased the risk of death by 31%, despite the fact that patients who originally received placebo were offered enzalutamide when they developed metastases.
Finally, in the mCRPC context, enzalutamide reduced the risk of death (compared to placebo) for patients who had both received docetaxel before (37% decreased risk in the AFFIRM study) and those who had not received chemotherapy before (29% decreased risk in the PREVAIL study).
Patients who should not take Enzalutamide
Patients with the following history should not take enzalutamide:
- A history of seizures
- Stroke
- Prior brain injuries
- Those whose cancer has spread to the brain
Also, patients with an allergy or hypersensitivity to enzalutamide should not receive it. As always, let your physician know if you have heart or kidney problems.
Instructions for taking Enzalutamide
Enzalutamide is prescribed at four tablets to be taken each day. These should be taken at the same time each day. They may be taken either with or without food.
Because enzalutamide can affect the liver, it may affect other medications that you are taking. This is particularly notable if you are taking medications for any of the following:
- high cholesterol
- pain
- epilepsy
- severe anxiety
- schizophrenia
- sleep problems
- heart problems
- high blood pressure
- thyroid problems
- gout
As your doctor discusses treatment options for advanced prostate cancer, make sure they are aware of all of the other medications that you are taking. Further, a cancer pharmacist can be very helpful in ensuring that there are no harmful interactions between taking multiple medications.
Side effects of Enzalutamide
There are both common (and often relatively mild) and uncommon (and sometimes severe) side effects. Among the more common side effects are:
- significant fatigue (tiredness)
- hot flushes
- breast tenderness and swelling
Men taking enzalutamide also have an increased risk of falling and breaking bones (fractures). Other side effects include muscle pains, diarrhea, and constipation.
There is a small increased chance of having a seizure for men taking enzalutamide. This risk is higher if:
- You have had seizures before
- Drink a lot of alcohol
- Have other health problems that affect the brain (a stroke, head injuries, or cancer spread to the brain)
- You are taking medications that make seizures more common
Many other side effects are possible and may be related to enzalutamide treatment.
As always, the content on this site is not intended to serve as specific medical advice. Discuss the specifics of your clinical situation and your treatment options with your doctor.
Apalutamide
More NHTs have become available since the introduction of abiraterone and enzalutamide. One such medication is apalutamide. Apalutamide, like enzalutamide, acts to block the action of testosterone by affecting the androgen receptor. It blocks the androgen receptor’s ability to carry out its functions in many ways including:
- Blocking its movement within the cell
- Blocking its ability to interact with DNA
- Blocking its ability to create signals within the cell. In this mechanism, apalutamide acts as a more potent version of prior anti-androgens such as bicalutamide.
Who might be prescribed Apalutamide?
Apalutamide is approved and has demonstrated survival benefits, for men with advanced prostate cancer in two different scenarios. First, in men with non-metastatic castration-resistant prostate cancer (nmCRPC; in which apalutamide will be started after the PSA is going up even though the testosterone is low while on ADT and there are no sites of metastasis on imaging), the SPARTAN study showed the using apalutamide reduced the risk of men developing metastases by 72%. Further, even though men who developed metastases received additional treatment at that time, starting apalutamide early before the metastases developed (at nmCRPC) reduced the risk of death by 22%.
Apalutamide may also be used in men with metastatic castration-sensitive prostate cancer (mCSPC; where apalutamide will be started at the same time as or shortly after ADT). In this setting, the TITAN trial showed that using apalutamide with ADT, as compared to ADT only, reduced a man’s risk of death by 35%.
Patients who should not take Apalutamide
Patients with the following history should not take apalutamide:
- History of seizures
- Stroke
- Prior brain injuries
Those whose cancer has spread to the brain may not be well suited to taking apalutamide.
Also, patients with an allergy or hypersensitivity to apalutamide should not receive it. As always, let your doctor know if you have heart or kidney problems.
Instructions for taking Apalutamide
Apalutamide is prescribed at four tablets to be taken each day. These should be taken at the same time each day and may be taken either with or without food.
Apalutamide may have effects on other medications that you are taking. As your doctor discusses treatment options for advanced prostate cancer, make sure they are aware of all of the other medications that you are taking. Further, a cancer pharmacist can be very helpful in making sure that there are no harmful interactions between taking multiple medications.
Side effects of Apalutamide
There are both common (and often relatively mild) and uncommon (and sometimes severe) apalutamide side effects.
Common side effects
- significant fatigue (tiredness)
- high blood pressure
- nausea, diarrhea
- heart disease
A notable risk of apalutamide that is less common for other similar medications is rash. This can often be treated with creams but sometimes requires other oral medications to treat.
Patients taking apalutamide may have issues with thyroid function that require them to take thyroid-replacement pills. They also may have an increased risk of falling and breaking bones (fractures). Other side effects include muscle pains, diarrhea, and constipation.
There is a small increased chance of having a seizure for men taking apalutamide. This risk is higher if you have had seizures before, drink a lot of alcohol, have other health problems that affect the brain (a stroke before, head injuries or cancer spread to the brain), or are taking medications that make seizures more common.
Many other side effects are possible and may be related to apalutamide treatment.
As always, the content on this site is not intended to as specific medical advice. Discuss the specifics of your clinical situation and your treatment options with your doctor.
Darolutamide
Darolutamide was the last of the approved NHTs to become available. Like enzalutamide and apalutamide, it acts to block the action of testosterone by affecting the androgen receptor. It blocks the androgen receptor’s ability to carry out its functions in a variety of ways including:
- Blocking its movement within the cell
- Blocking its ability to interact with DNA
- Blocking its ability to create signals within the cell
In contrast to apalutamide and enzalutamide, darolutamide cannot access the brain so it has fewer brain-related side effects.
Who might be prescribed Darolutamide?
Darolutamide is approved and has shown survival benefits for men with advanced prostate cancer in two different scenarios. First, in men with non-metastatic castration-resistant prostate cancer (nmCRPC) in which in darolutamide will be started after the PSA is going up even though the testosterone is low while on ADT and there are no sites of metastasis on imaging, the ARAMIS study showed that using darolutamide reduced the risk of men developing metastases by 59%. Further, even though men who developed metastases received additional treatment at that time, starting darolutamide early before the metastases developed reduced the risk of death by 31%.
Darolutamide has also, very recently, been approved for men with metastatic castration-sensitive prostate cancer in combination with docetaxel chemotherapy (mCSPC; where darolutamide will be started at the same time as or shortly after ADT) based on the ARASENS study. In this study, the authors compared the combination of darolutamide with docetaxel chemotherapy and ADT to docetaxel chemotherapy and ADT. This study showed that the so-called “triplet” combination with darolutamide, chemotherapy, and ADT reduced the chance of death by more than 32% compared to chemotherapy and ADT. This triplet approach was approved by the FDA on August 5, 2022.
Patients who should not take Darolutamide
There are a few reasons why some patients should not take darolutamide. Patients with an allergy or hypersensitivity to darolutamide should not receive it. As always, let your doctor know if you have heart, liver, or kidney problems. Your doctor may choose to give you a lower dose of darolutamide in some of these circumstances. Importantly, unlike apalutamide and enzalutamide, men with a history of seizures or a past stroke may take darolutamide safely.
Instructions for taking Darolutamide
Darolutamide is prescribed as two tablets to be taken two times each day. These should be taken at the same time each day. They may be taken either with or without food.
Darolutamide may have effects on other medications that you are taking. As your doctor discusses treatment options for advanced prostate cancer, make sure that they are aware of all of the other medications that you are taking. Further, a cancer pharmacist can be very helpful in making sure that there are no harmful interactions between taking multiple medications.
Side effects of Darolutamide
There are both common (and often relatively mild) and uncommon (and sometimes severe) side effects. Among the more common side effects are significant fatigue (tiredness), pain in your arms or legs, and rash.
Darolutamide may also increase the chance of heart disease and may have effects on blood tests for liver function. Importantly, darolutamide does not increase the risk of seizures, falls, or fractures (broken bones), unlike apalutamide and enzalutamide.
As always, the content on this site is not intended to as specific medical advice. Discuss the specifics of your clinical situation and your treatment options with your doctor.
Is this an accurate definition?
After being diagnosed with prostate cancer, your urologist may recommend treatment with either surgery or radiotherapy. Both of these represent good treatment options for many men who are diagnosed with prostate cancer that has not spread outside the prostate. Additionally, for some men whose disease has spread, radiation therapy to the prostate may still be appropriate.
What is radiation therapy?
Radiation therapy is a cancer treatment that uses the effects of radiation (high energy rays or particles) to kill cancer cells and shrink tumors. In men with prostate cancer, radiation therapy may be used on its own or as part of a combination of the first treatment along with hormone therapy. It may be used after surgery for those men whose cancer is not removed completely or comes back. Finally, it can also be used to help control cancers and prevent or relieve symptoms for those with more advanced disease.
How is radiation therapy given?
Generally speaking, there are two main ways that radiation therapy is given for prostate cancer: external beam radiotherapy (also known as EBRT) and brachytherapy.
External beam radiation therapy focuses beams of radiation on the prostate gland and the tumor. The experience of receiving each treatment is kind of like having an X-ray or a CT scan. However, the radiation used is much stronger.
Over the last two decades, there have been major advances in the technology that radiation oncologists (radiation therapy doctors) can use to target the prostate and prostate cancer while avoiding the healthy normal tissues nearby. These approaches, called intensity-modulated radiation therapy (IMRT), are commonly used. They may also do repeated imaging before each treatment or use systems to track internal seeds or the surface of a patient’s skin, which is called image-guided radiotherapy (IGRT).
These treatments are often given over the course of weeks. More recently, radiation oncologists have focused on giving fewer, higher doses of radiation therapy for prostate cancer. This is a process called stereotactic body radiation therapy (SBRT). This may be appropriate for some men with prostate cancer but is not right for all men.
Each of the types of radiation therapy listed so far uses a “photon” to deliver energy from the radiotherapy machine to the prostate tumor. There also are machines that use “proton beams.” Proton beam radiotherapy is much more expensive and has less long-term evidence than photon radiotherapy. For prostate cancer, it is not clear that this approach gives better outcomes.
When you have external beam radiotherapy, the radiation therapist will take images to make sure that you are correctly positioned to target the treatment in the right place. Once you are positioned, the radiation therapist will begin treatment. This only takes a few minutes, but you will need to stay as still as possible. While you are being treated, the machine will not touch you and you should not feel anything. After treatment is done, you can leave the treatment center and return to your normal activities.
The second way of giving radiotherapy is called brachytherapy. This is a form of internal radiotherapy. Brachytherapy involves placing a radioactive source directly into the prostate gland and the tumor. These implants may be permanent (seeds that are left in the body; low dose rate brachytherapy) or temporary (high dose rate brachytherapy).
While external beam radiotherapy can be done while patients are awake, brachytherapy requires an anesthetic (either a general anesthetic or spinal) for the surgery to place the radioactive implants. Brachytherapy may be given by itself or in combination with external beam radiation.
How do I choose?
There are pros and cons to each prostate cancer treatment. Radiation for prostate cancer can irritate the bladder and bowels. Symptoms can include:
- Pain or a burning sensation when urinating (peeing)
- The need to pee often
- Blood in the urine (known as hematuria)
- Feeling like you need to pee but very little comes out
- Stomach bloating or cramps
- Thin, watery, or loose stools
- Blood in the stool
- Feeling an urgent need to have a bowel movement
However, these symptoms don’t usually last long and only a small number of men have long-term problems with these issues after treatment.
Unlike surgery, radiation therapy doesn’t tend to affect sexual function right away. But, over time, sexual function may be affected as a man ages. This is because the same nerves that are affected after surgery are also affected long-term after radiotherapy). Some men also note fatigue when they are receiving radiation therapy.
There may be certain reasons that mean you are not able to receive specific kinds of radiation therapy. These can include the size of your prostate or other medical conditions or surgeries you’ve had or symptoms you are experiencing. You should meet and discuss your treatment options with your doctor and find out the details you need to make the right choice for you.
If you are diagnosed with prostate cancer, your doctor may recommend hormonal treatments called androgen deprivation therapy (ADT). Over 80 years ago, a team of researchers discovered that the hormone testosterone drives prostate cancer growth. They learned that prostate cancer could be treated by decreasing levels of testosterone in the body of a man with prostate cancer.