Hormone Therapy as Treatment for Prostate Cancer
Dhwani Patel, Ching Yung Yuan, Mackenzie Smith
November 2023
Prostate cancer is a top contributor to cancer-related deaths in men, second only after lung cancer (1). According to Canadian Cancer Statistics, approximately 1 in 8 Canadian men will develop prostate cancer during their lifetime (2). The population of men around the age of 65 are especially vulnerable to this type of cancer.
The prostate is a male reproductive gland located in front of the rectum and plays a role in semen production. Under normal circumstances, male sex hormones (androgens), such as testosterone, are required for the prostate gland to grow. In prostate cancer, the same androgen hormones cause uncontrolled growth of cancer cells (3). Thus, hormone therapy is one of the common treatments for prostate cancer, along with radiation therapy and chemotherapy. Typically, radiation therapy is used in early-stage prostate cancer due to its higher precision in targeting cancer at the site of the prostate (4). On the other hand, chemotherapy is often used for prostate cancer that has spread to other organs and is associated with more adverse side effects such as fatigue, hair loss, nausea and vomiting. There are different types of hormone therapy that are either used alone or in combination with either radiation or chemotherapy.
Hormone therapy uses drugs to block the effects or overall production of androgen hormones. It typically begins with drugs that reduce the amount of androgens produced by the testicles. This type of treatment is referred to as androgen deprivation therapy (ADT) (3). When ADT stops working, other hormone therapies that block the action of androgens, called antiandrogen therapies, are used (3).
There are some challenges with the current, available therapies for prostate cancer. For ADT specifically, patient perspectives have revealed hesitancy about using ADT due to its systemic impacts on the body. Blocking the production of androgens like testosterone in the body can lead to side effects such as decreased bone density and muscle mass, decreased libido, sexual dysfunction, and hot flashes. Studies show that prostate cancer patients are more willing to live with an enhanced quality of life and slightly shorter overall survival than a longer life with a poor quality of life (5). Another issue with hormone therapies, in general, is drug resistance, where cancers become unresponsive to drugs and continue to grow despite the application of hormone therapies. Although this is uncommon, drug resistance is still a major contributor to the drop in 5-year net survival of prostate cancer patients, which goes from a high of 101% net survival in stage 1 prostate cancer to 41% net survival in stage 4 cancer. Stage 4 prostate cancer is also known as metastatic castration-resistant prostate cancer (mCRPC) (6).
Overall, there is a lot of incentive for the medical community to develop new strategies for successfully treating prostate cancer. The undesirable side effects of ADT and the drug resistance problem in mCRPC are two prominent drivers of research and innovation.
One major area of exploration is the utilization of technology to predict the best treatment option for patients. For example, the ability of artificial intelligence (AI) technology to process vast amounts of data is being co-opted for a variety of cancer treatments. In prostate cancer, AI can be used to compare and contrast patient information against existing databases to form predictions about whether ADT would work well for a particular patient (7). This way, AI can help avoid unnecessary application of ADT if there are potentially poor results. Alternatively, AI can also increase the efficiency of treatment by identifying potential drug candidates that will be more effective for a specific patient (7). This is especially important for a more personalized treatment approach, which would allow treatment options to be specifically tailored to each patient for maximal treatment efficiency.
Additionally, genetic testing for prostate cancer risk factors is also gaining traction and is strongly recommended for men with known prostate cancer risk factors. This includes individuals who are middle-aged, have a family history of prostate, breast, ovarian, colon or pancreatic cancers, or have African-American heritage (8). Regular screening increases the chances of detecting cancerous lesions at earlier stages so treatment can begin sooner (9). Applying treatment interventions at earlier points of cancer development leads to higher efficacy and efficiency of treatment, along with faster recovery. As well, lower-intensity drug regimens can be used when the cancer is still at an early stage, which means fewer side effects for the patient (9). Due to these benefits, more patients are being recommended for genetic assessments. Screening for prostate cancer should typically begin around age 50, but can be earlier for certain high-risk populations. For more information on the risk factors and importance of screening for prostate cancer, please visit the Canadian Cancer Society website.
New hormone therapies are also being developed as alternatives or supplementary treatments to ADT. Aside from undesirable side effects, another problem with ADT is that it does not completely eliminate androgens from the body. In some cases, the small number of leftover androgens in the bloodstream can still stimulate tumour growth. Enzalutamide is a hormone therapy that works by blocking hormone function. When ADT and enzalutamide are used together, the former can help deplete hormone levels while the latter makes the remaining hormones nonfunctional (10). In a phase 3 trial involving prostate cancer patients with a high risk of cancer recurrence, ADT in combination with enzalutamide reduced the risk of cancer resurgence and patient death by 58% compared to ADT alone (11). When enzalutamide was taken alone it was found to be 37% more effective than ADT. Some patients would much prefer to avoid ADT altogether in favour of taking only enzalutamide to avoid the ADT side effects. But more importantly, adding enzalutamide greatly increased treatment efficiency and the patient’s quality of life.
To target the problem of drug resistance (especially in mCRPC), new drugs are being introduced for the treatment of prostate cancer. mCRPC is resistant to a lot of anticancer drugs in part because of the tumour’s ability to ‘hijack’ healthy immune cells. mCRPC uses the immune system to avoid the impact of drugs through a complicated system of interactions. AZD5069 is a newly approved drug designed to prevent those interactions between cancer cells and immune cells (12). Once the interactions are blocked off by AZD5069, the tumour can no longer take advantage of immune cells. One of the benefits of AZD5069 is in reversing mCRPC drug resistance. This means when AZD5069 is added, drugs that previously did not work well on mCRPC now can suppress the tumour. Thanks to the development of ‘sensitizing’ drugs like AZD5069, patients with mCRPC can access more treatment options for their cancer (12).
As discussed, finding new directions for research requires scientists to consider a combination of both clinical challenges and patient perspectives. For prostate cancer, patient perspectives regarding quality of life under ADT treatment and cancer treatment have led to innovations such as AI to match patients with the most effective drug option, and genetic testing to catch prostate cancer as early as possible. Drug development also focuses on improving the patient experience by introducing new drugs with lessened side effects, such as Enzalutamide, as well as sensitizing drugs such as AZD5069. Feedback from the patient population is vital in driving technological advances, the creation of screening protocols, and research for new anticancer drugs. As such, patient outreach is extremely important to give the scientific and medical community a better perspective on where the needs are and how to meet them.
References
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