Prostate cancer is one of the major cancer types that cause mortality and it is the second most incident cancer type in men worldwide. According to World Health Organization (WHO), prostate cancer is the second most diagnosed cancer type in men with 1.3 million diagnoses in 2018 and the fourth most diagnosed cancer type in total sex-independent cases.
Prostate cancer is classified based on factors such as aggressiveness, grade of the cancer and age of the patient. Mainly, prostate cancer classes can be listed as aggressive and nonaggressive prostate cancer (PCa), high and low-grade PCa, early onset and indolent PCa (occurring after age of 55). The class and grade of the prostate cancer has a big role in prognosis of the disease and mortality because patients who are diagnosed in early stages have higher survival rates.
Development of prostate cancer is multifactorial which means that it is dependent on more than one condition; both genetic and environmental factors have essential roles as well as diet and age. According to American Cancer Society, 6 in 10 prostate cancer patients are 65 or older. Additionally, average diagnosis age is 66 and cases under age of 40 are rare. Correlation of prostate cancer with age can be described with change in testosterone:oestrogen ratio with age.
In men, serum testosterone level declines as the age gets older but oestrogen level is constant. It causes a change in testosterone:oestrogen ratio which is supposed to be one of the main reasons of prostate cancer. Testosterone is an androgen which binds to androgen receptors (AR). As testosterone level decreases, AR level increases to stabilize the AR-dependent signaling which causes DNA damage and development of prostate cancer consequently. In addition to this, environmental factors such as radiation and cellular stress cause cells to divide in an uncontrolled manner and may cause prostate cancer.
Diagnosis of Prostate Cancer
Diagnosis of prostate cancer, especially early detection of it, is important for good prognosis of the disease. In addition, not only late diagnosis causes mortality but also overdiagnosis, which means diagnosis of a person as prostate cancer when he is healthy, and overtreatment; treatment of an individual as a result of screening whereas he would not have any symptom without treatment have huge impact. Serum Prostate Specific Antigen (PSA) level and biopsy are currently used for diagnosis of prostate cancer.
First step in diagnosis is checking the PSA level if it is out of the normal/expected range. Secondly, biopsy is performed if PSA level is out of range and grade of the cancer is identified. However, for some patients despite the fact that they have high PSA levels, the biopsy results show that there is no tumor in prostate or benign hyperplasia is detected so the person with high PSA level comes out to be healthy. This is because PSA level can change depending on many factors in addition to cancer so it can be misleading.
Therapy of Prostate Cancer
There are main therapy options in prostate cancer; radical prostatectomy, radical radiotherapy, conservative management, immunotherapy, hormonal therapy and chemotherapy (docetaxel). Radical prostatectomy means removing the tumor from the body by surgery. On the other hand, radical radiotherapy is the method that high-energy X-rays are used and it is a non-surgical therapy. On the other hand, conservative management is watching the disease progression and healing the symptoms rather than treating it.
Immunotherapy has been one of the best choices for therapy of prostate cancer in some patients and its efficiency depends on the cancer stage and history of the patient. Prostate has many tumor-associated antigens which can be targeted for vaccines. This is the reason that prostate cancer is a good cancer type for developing therapeutic cancer vaccines. In addition, development of prostate cancer is relatively slow so there is time for development of anti-tumor immune response in the body which is an advantage for cleaning the tumor. However, prostate cancer cells can prevent immune response by making the antigen presentation inefficient by downregulating human leukocyte antigen class I.
Sipuleucel-T (Dendreon Corp.) is the therapeutic vaccine approved by the US Food and Drug Administration (FDA). Phase III researches show that it is most efficient on early prostate cancer because there was an increase in overall survival of patients with early prostate cancer. The mechanism of this therapeutic vaccine is not understood completely and it is known that tumor sizes or PSA levels are not affected but overall survival increases. For high-risk prostate cancer patients, combinational therapies such as chemotherapy and hormonal therapy (enzulatamid) combinations are applied frequently.