Key takeaways
- You may need to switch prostate cancer treatments if the cancer progresses, side effects become unmanageable, or current medications interact negatively with other drugs.
- Signs that your current prostate cancer treatment may no longer be effective include changes in radiographic imaging, worsening PSA blood test trends, or new and worsening symptoms like bone pain or fatigue.
- Open and honest communication with your oncologist is crucial when considering a treatment switch, allowing you to discuss your goals, potential side effects of new treatments, and overall quality of life.
Switching treatments in prostate cancer is common for many different reasons. The treatments in advanced prostate cancer range from injections to oral medicines to intravenous chemotherapy to radiopharmaceutical medications administered intravenously.
The most common reason for switching treatments in prostate cancer is due to the cancer worsening (spreading/growing larger) despite being treated with a medicine. We call this “progression of the cancer.”
Many oncologists refer to these options as “first-line” or “second-line” therapy, depending on how many times a patient has had to switch their cancer therapy. When a switch is made from one line of therapy to the next, because of the condition’s progression, the current medicine is usually stopped and the next medicine is started. This typically occurs without any delay.
Another common reason to switch treatments in prostate cancer is if you have intolerable side effects. All of the medicines in prostate cancer have potential side effects and not everyone is guaranteed to have the listed potential side effects.
One of the most common medicines used to treat prostate cancer is called leuprolide (Lupron) injection. The prescribing information lists many side effects including suicidal ideation; however, most patients do not experience these thoughts. But for someone who is having these thoughts, discussing alternative treatment options with the care team is critical.
If you’re switching medicines because of intolerable side effects, it’s likely that your practitioner will first attempt to reduce the dose or frequency of the medicine prior to stopping it all together. This is mostly done when the side effects are not life-threatening:
- intolerable fatigue
- hot flashes
- diarrhea
- joint aches
- weakness
If the intolerable side effect is life-threatening (i.e., suicidal ideation), it is most appropriate to discontinue the medication without attempting to reduce the dose of the medicine.
Another reason for switching medicines when treating prostate cancer is related to “drug-drug interactions” or DDI. This happens when two medications interact in a way that changes how one of them is processed in the body, potentially causing either more side effects or reduced effectiveness.
In this case, there may be an alternative medicine in the same class that has the same mechanism of action as the initial drug but which does not interact with other medications.
For example, in prostate cancer patients with a history of blood clots who are taking the blood thinner apixaban, there is a potential drug–drug interaction with apalutamide, an oral medication commonly used to treat prostate cancer.
Taking these two medications together can make the blood thinner work less well, which could raise the risk of blood clots.
Therefore, an oncologist can consult with a pharmacist about which medications in each of the classes for Apixiban or Apalutamide would be reasonable alternatives so that a DDI does not occur.
If a switch is to be made, it usually only requires one medication change. The switch can occur instantly or after a little bit of delay (“wash out period”) to delay supratherapeutic (higher-than-safe) levels of the drug if the previous interaction was leading to a high level of the medicine in the blood.
The most common signs that prostate cancer treatment is no longer working is a larger burden of cancer on radiographic images, new cancer lesions on radiographic images, or worsening serum tumor markers. In prostate cancer, the most commonly used radiographic imaging to locate the cancer and assess its burden/size is a PSMA PET scan or CT scan and bone scan.
MRI could also be used, but it’s less common. When a patient has advanced prostate cancer, these radiographic images are obtained in intervals to measure if the medication is working. These intervals can be months apart. Each scan is compared to the prior to see if the tumor/cancer changed in size/location in that interval period.
We call this a “restaging scan.” Sometimes scans are not as necessary in following advanced prostate cancer as they would be with other types of cancer because of a fairly reliable tumor marker (blood test) called
The PSA blood test is usually obtained every 3 to 6 months and is compared to the most recent PSA results to assess whether the treatment is still working or if the treatment has stopped working. The overall trend of the PSA is more important than the absolute number itself.
The doubling time of a PSA (PSADT) has also been shown to be predictive in when prostate cancer is becoming more aggressive and likely to spread.
If you experience worsening symptoms from the cancer, it may be that a medication has stopped working. Examples include complaints of new bone pain, increased fatigue, decreased appetite, or worsening urinary symptoms.
Usually, these symptoms would persist and worsen until the treatment is changed if the symptoms are secondary to
Prostate cancer hormonal blockade therapy was historically treated with surgical castration of the testicles. Eventually a medical form of castration was discovered in the form of medication that manipulates the hormone GnRH (gonadotropin-releasing hormone) agonists or antagonists, which decreases the production of testosterone.
A GnRH agonist will cause surging testosterone for a small period of time before leading to an eventual decrease in testosterone. A GnRH antagonist will cause a quick decline in testosterone.
An oral alternative, relugolix (Orgovyx), is a GnRH antagonist. It carries many of the same side effects as injectable GnRH therapies but does not cause injection-site reactions such as pain or swelling.
These oral treatments, such as reluoglix, have side effects similar to injectable GnRH therapies, including:
- fatigue
- hot flashes
- sexual dysfunction
- bone loss
- heart problems
The drawback to oral GnRH antagonist like relugolix is having to remember to take the pill every day. The benefit is there are no injection site side effects.
There are other oral medicines which can manipulate the androgen receptor or androgen synthesis. These have more unique side effects andare not medications that can replace the injectable hormone blockade therapies like GnRH agonists/antagonists as they diminish the prostate cancer in different ways.
When prostate cancer treatment is working well and diminishing or controlling the cancer, but the side effects are significantly reducing a person’s quality of life, it can be difficult to know how to proceed.
Many patients will be treated when there are no further options or the cancer has spread to distant parts of the body. The treatment in this case may be palliative, placing the patients’ QoL as the utmost priority.
Hormonal blockade with other medications to treat prostate cancer commonly carry unique side effects including but not limited to:
- fatigue
- hot flashes
- sexual dysfunction
- joint discomfort
- lack of concentration/motivation
These side effects can lead some people to question whether continuing treatment to extend their life is the right choice. It’s an understandable and reasonable concern.
Discussing options with your oncologist about goals and expectations is wise. Voicing one’s opinion when side effects from the medicine are starting to effect the QoL is essential in the doctor-patient relationship.
A conversation with the oncologist about treatment goals can help set expectations early.
The first priority of the patient when a treatment is changed is to know why the treatment was changed. Treatment changes can happen due to:
- progression of the cancer
- lab abnormalities
- intolerable side effects
- medicine-to-medicine interactions
It is reasonable to ask the oncologist if the new treatment carries similar or different side effects than the current treatment.
Patients should also ask about the likelihood that the switch will achieve the intended goal, how long the new treatment is expected to be used, how it is administered, and whether it needs to be started right away or after a short washout period from the previous medication.
Switching prostate cancer treatments is common and usually happens because the cancer progresses, side effects become intolerable, or medications interact with each other.
Monitoring through scans, PSA trends, and symptoms helps determine when a change is needed. Open communication with your oncologist about goals, side effects, and quality of life is key when considering a switch.
Dr. Sheel Patel is an ABMS board certified physician in hematology, oncology, and internal medicine. Dr. Patel is a practicing physician at the Orlando VA Medical Center in Florida. He specializes in genitourinary oncology.