Which Treatment Should Be Chosen for Newly Diagnosed Stage 4 Prostate Cancer?

Newly diagnosed disease not previously treated with hormones, metastatic prostate cancer is defined as hormone-sensitive prostate cancer. This group includes patients with metastases to bone and other organs and patients who previously, for prostate cancer, without any hormonal treatment , underwent surgery or local radiotherapy and subsequently developed metastatic recurrence.

Two important advances have occurred in recent years in treating recurrent or newly diagnosed metastatic prostate cancer not previously treated with hormones:

• the first is adding to conventional hormonal treatment the chemotherapy drug docetaxel ,
• the other is adding to conventional hormonal treatment abiraterone acetate , a new-generation hormonal treatment.

Both strategies have shown superiority over the conventional hormonal treatment used for years in high-risk patients. These two discoveries have also raised an important question.

-Related topic: What Is Prostate Cancer Risk Classification?

Which of these two treatment methods should be chosen?

For nearly 80 years, androgen (testosterone)-suppressing treatments have been accepted and used as standard treatment for hormone-sensitive metastatic prostate cancer. Medicines used to suppress androgens stop signals from the brain to the testes (the hypothalamic-pituitary-testicular axis). A GnRH analog or antagonist that interrupts this signal is selected. Administering these hormone treatments every three months stops testicular androgen production, and this method is called medical castration . Another method is surgical removal of the testes, but this is not often preferred because it causes psychological trauma; similarly effective medical castration is used instead.

Medical castration produces responses in %80-90 of patients. However, disease control lasts 2 years and median survival is around 40-50 months. This duration is longer in patients with low metastatic burden or a low Gleason score , while it may be shorter in high-risk patients.

The main reason disease cannot remain controlled over time is what prostate cancer cells develop against hormone suppression, called castration: resistance.

Studies show that the main reason for resistance to hormonal treatment is prostate cancer cells becoming able to survive on the very small amounts of adrenal androgens produced outside the testes. Two important drug groups developed in recent years have sought, successfully, to overcome this resistance. The first of these new-generation hormonal treatments is abiraterone (brand name Zytiga). It acts on the adrenal glands, stopping production of cortisol and androgens synthesized from cholesterol. Combined with medical castration, abiraterone eliminates the androgens prostate cancer cells need. It not only cuts adrenal androgen secretion but also prevents autonomous androgen production acquired by prostate cancer cells over time. Low-dose cortisone is given with abiraterone to replace cortisol no longer produced in the adrenal glands, correcting this vital deficiency.

Development of abiraterone began in the 1990s; it first showed success after chemotherapy in patients resistant to medical castration and, in 2006, received FDA approval. Subsequent studies used it before chemotherapy in castration-resistant patients, and finally LATİTUDE and STAMPEDE tested it as first-line treatment in hormone-sensitive metastatic prostate cancer.

The successful results of these two studies were sufficient to challenge the single hormonal treatment used for nearly 80 years, particularly in high-risk hormone-sensitive prostate cancer. In LATİTUDE, median disease control improved from 15 to 33 months with abiraterone, more than doubling, while death risk decreased significantly by %37.

The success of abiraterone in hormone-sensitive metastatic prostate cancer raised an important question:

Can an oral hormonal treatment replace chemotherapy for hormone-sensitive metastatic prostate cancer?

After 2014, studies adding the chemotherapy drug docetaxel to medical castration produced positive results. CHAARTED and STAMPEDE found survival increases of more than 10 months with added docetaxel. Survival in newly diagnosed hormone-sensitive metastatic prostate cancer therefore approached 60 months, nearly 5 years. The difference was particularly pronounced with high tumor burden and smaller when metastatic burden was low.

High-risk patients were the group benefiting from both strategies. Analyses of indirect comparisons found similar efficacy but different side effect profiles.

Treatment-specific side effect profiles may guide patient selection.

Although patients tolerated abiraterone well, cardiac, liver and vascular side effects increased; docetaxel recipients could experience low blood counts and infection (neutropenic fever), nerve damage in the hands and feet (peripheral neuropathy) and, rarely, treatment-related death.

Docetaxel's cost is lower, whereas abiraterone's cost, although varying by country, is markedly higher. However, in March 2018, JCOpublished a phase-2 clinical trial showing that, when abiraterone is taken with a low-fat diet , instead of the usual daily dose of 1000 mg (4 tablets), 250 mg (1 tablet) could be taken. This means that out of 4 parts of the cost, 3 could be eliminated simply through a dietary change.

Physician experience, patient preference and reimbursement coverage are other important factors in choosing docetaxel or abiraterone.

Nevertheless, treatment availability, social support for the patient and family, and control of accompanying illnesses are important determinants of treatment choice.

The encouraging point is the remarkable positive change and increase in treatment options for patients with metastatic prostate cancer.

It is extremely important that all physicians treating prostate cancer closely follow and absorb rapidly changing scientific data, and that patients and families trust modern medical practitioners familiar with these processes and recognize the expanding treatment options.

RELATED TOPICS

Advances in Prostate Cancer Treatment—2017 and 2018

Effective Results with Actinium Alpha Therapy in Stage 4 Prostate Cancer

Testosterone Deficiency Symptoms, Treatment, Andropause and Prostate Cancer

How Does a High-Fat Diet Trigger Prostate Cancer Spread?