Pain relief for men with prostate cancer

[Wendy_Winnall]

Pain can be a big issue for men with prostate cancer. It can be both a symptom of the cancer and a side effect from its treatment. For men with metastatic prostate cancer, bone pain is often one of their most difficult problems. This week’s blog looks at the latest research behind pain management for men with prostate cancer.

How does prostate cancer cause pain?

Pain is both a symptom of prostate cancer and a side effect of its treatment. It is often the most difficult part of living with the disease. Pain stops men from doing many daily activities, makes them miserable and unable to enjoy life. Fortunately, there are many good options for pain management. There is also ongoing research to help reduce the terrible effects of pain for men with prostate cancer.

Pain can be a problem for men with prostate cancer at different stages and for many different reasons.

Localised prostate cancer detected by a PSA test may come with no pain or other symptoms. Some men with localised prostate cancer experience pain during urination or in the lower back. Pain can also be a side effect of treatment for localised disease. Pain is often experienced in the short term after prostate surgery, and soreness can occur after radiotherapy.

Men with advanced prostate cancer are more likely to experience pain, particularly when they have metastatic tumours in their bones. Pain is often felt in the spine and pelvis, due to bone tumours. Pain can also result from tumours in lymph nodes and other regions such as their liver and lungs. Some men experience pain in other regions due to tumours pressing on their spinal cord, damaging nerves.

Aside from the pain caused by tumours, pain can also result from the treatments for advanced prostate cancer. Some side effects from chemotherapy and hormone therapy (androgen deprivation therapy; ADT) may cause pain. Docetaxel and cabazitaxel chemotherapy can cause nerve damage called peripheral neuropathy. This causes pain or numbness in the hands and feet. ADT leads to weakening of bones, which may also cause pain.

Treating and managing pain for men with prostate cancer

Most men with advanced prostate cancer are not living in constant pain. Treatments such as ADT and chemotherapy reduce the size of tumours, which relieves the pain they cause. A pain management plan helps men with metastatic tumours to live in reasonable comfort, despite their tumours. These plans usually provide regular medication to take, goals and strategies for pain relief and a strategy for relieving breakthrough pain (sudden pain that comes on despite current pain relief).

Men with prostate cancer who are experiencing considerable pain should discuss this issue with their doctors as soon as possible. For men with prostate cancer who need long-term or strong pain relief, there are numerous options for managing their pain. Some of these options are:

Common pain relief drugs Paracetamol and non-steroidal anti-inflammatory drugs (NSAIDS), such as Ibuprofen, are commonly used for mild pain.   

Opioids For stronger pain, opioids are often used. Opioids used in Australia include morphine, oxycodone, tramadol and fentanyl. Codeine (found in Panadeine) is a mild opioid used to manage weak or moderate pain. Fast-acting drugs, such as Endone, can be taken for breakthrough pain. This is sudden pain that comes on despite taking everyday pain relief. Adverse effects from opioids include addiction, drowsiness, nausea, constipation, vomiting, dry mouth and more. Oncologists pay careful attention to managing these side effects and have strategies for minimising and preventing them. Cancer Council NSW has some useful information about opioids for cancer patients.

Corticosteroids These are anti-inflammatory drugs that are also useful in counteracting the negative effects of chemotherapy. Corticosteroids can also reduce the pressure of tumours in the spine. Corticosteroids have side effects and their use needs to be carefully monitored by doctors.

Radiotherapy Radiotherapy can be used to treat metastatic tumours. A short-term treatment of painful bone tumours can slow or stop their growth, relieving the pain they cause in the long-term.

Treating the cancer Treatments such as hormone therapy (ADT), chemotherapy or radium-223 (Xofigo) that successfully reduce the size of tumours should reduce the pain they cause. As this takes time, it is a long-term pain-relief strategy.

Bisphosphonates and denosumab ADT and bone tumours can weaken the bones, causing pain. Drugs such as bisphosphonates and denosumab help to strengthen weak bones and slow further damage, reducing pain.

Complimentary therapies Exercise, massage, acupuncture and other complimentary therapies (those used alongside conventional medical therapies) may bring some pain relief to men with prostate cancer.

Exercise There is evidence that tailored exercise programs can help reduce pain and have many other benefits for men with prostate cancer. Your doctors should be able to recommend an exercise physiologist who can work with you to develop an appropriate program for your needs.

Other treatments Men who are having chemotherapy may be more susceptible to infections that cause pain. Treating these infections, such as by antibiotics, can help reduce the this pain.

Palliative care Palliative care is a combination of therapies aiming to give optimal care to a person who has a life-threatening illness. Palliative care is much more than end-of-life care. More information about palliative care can be found at this research blog. While there is more to palliative care than pain relief, palliative care providers are experts in pain relief for cancer.

There are other methods used to help with pain, depending on the specific circumstances in which the pain arises. PCFA recommends discussing pain management at length with your doctors for information specific to your own needs.

Latest research in pain management

As for other types of side effects, pain management for men with prostate cancer is a subject of ongoing research. Two recent studies of prostate cancer pain have been published in top journals.

COMET-2 trial: Trialling pain relief by Cabozantinib for men with metastatic castration resistant prostate cancer.

Most clinical trials for prostate cancer treatments test whether these new drugs improve survival rates or prevent the cancer from progressing. Pain relief is also measured, but not as a primary objective. A reduction in pain is rarely the most important aim of the trial. Given the importance of pain relief for men with bone tumours, it’s encouraging to see some clinical trials now have the primary aim of reducing pain. The COMET-2 trial is one such study.

119 men were enrolled and treated in the COMET-2 trial. They lived in the USA, Canada, UK and Australia. These men had mCRPC, including tumours in their bones. Their disease had progressed after treatment with docetaxel chemotherapy and either Abiraterone (Zytiga) or Enzalutamide (Xtandi). Their pain from the bone tumours required continual management with opioid drugs.

61 of the men were treated with cabozantinib and 58 with mitoxantrone plus prednisone. Cabozantinib is a chemotherapy drug that is a tablet, taken once a day. Cabozantinib was tested to see if it was more effective that mitozantrone/prednisone. Mitoxantrone is chemotherapy drug delivered intravenously every 3 weeks. Prednisone is an anti-inflammatory taken as a tablet, twice a day. Prednisone reduces some of the side effects of chemotherapy.

The primary objective of the COMET-2 trial was a reduction in pain. The researchers wanted to know if Cabozantinib was more effective than Mitoxantrone. Pain was measured before the medication, then after 6 weeks and 12 weeks. Pain was measured using a standard survey, validated and used in many other studies. The researchers hoped that their treatments would lead to at least a 30% drop in the “average daily worst pain intensity”.

The results showed that a small proportion of men saw their pain significantly reduced in response to medication. 15% of men taking Cabozantinib and 17% of men taking Mitoxantrone experienced a 30% or greater drop in pain intensity. There was no difference between the effectiveness of the two drugs.

Unfortunately, there were side effects from the treatments. All patients experienced one or more adverse effects. Some of the side effects included high blood pressure, diarrhoea, fatigue, shortness of breath and vomiting. Some of the men needed to stop using their drug due to the side effects.

This trial didn’t show that Cabozantinib was a better treatment for pain than Mitozantrone. But the results and lessons learned during the running of this trial have paved the way for more successful trials in the future that are aimed at reducing pain for men with mCRPC.

The ORIOLES initiative

Researchers from Johns Hopkins University School of Medicine in the US studied the use of opioid pain relief after prostate surgery. Opioid over-use and addiction are important concerns at the moment. In the USA, 40,000 people die each year under opioid-related circumstances. Opioid addiction can sometimes start after surgery.

The US study examined the ORIOLES initiative. This program was implemented at the Johns Hopkins Medical Institutes to measure prescriptions, use and disposal of opioids after prostate surgery. The experiences of 205 patients were studied. 56 had open surgery and 149 had robotic-assisted surgery. Their operations were performed by one of nine different surgeons available. 20% of these men had pain associated with their prostate cancer at the time of diagnosis.

Most of the men (90% of them) were prescribed oxycodone after their surgery. They were provided with an average of 227mg of drug to take home. The researchers then followed-up after 30 days to ask if they had taken the drug and what happened to the remainder.

Results from this study showed that an average of 52.5mg of drug was used by these men for pain relief after their surgery. They used only 23% of the drug provided to them. This was no different for the men who had robotic-assisted compared to open surgery. Less than 5% of the men reported pain continuing up to 30 days, but none were still using the medication by 30 days.

The results of this study also showed that regardless of the amount of pain each man had, if he was provided with a larger amount of pain relief, he was more likely to use it.

Only 9% of patients appropriately disposed of their left-over drugs. Appropriate disposal was considered to be dropping off at a pharmacy or clinic, or flushing the left-overs down the toilet. So 77% of the opioid drug wasn’t used, and was not properly disposed.

Overall, these results suggest that men are being over-prescribed opioid pain relief, have a lot left over and are not disposing of it properly after prostate surgery. The researchers suggest that a better approach to prescription is necessary. The ORIOLES initiative is now using this data to set up clinical prescription guidelines and provide better information to patients about use and disposal of these drugs.