Prostate Cancer Symptoms: Understanding the Progression and Potential Impacts of Delayed Diagnosis.

In the early stages, most prostate cancer patients do not exhibit any noticeable symptoms. However, in the middle stages, there may be urinary obstruction, such as difficulty urinating, the need to exert force to urinate, frequent urination, and other symptoms. The skeleton is the most common organ for prostate cancer metastasis, and in advanced stages, patients may experience back pain or pathological fractures, depending on the severity. Due to the lack of obvious symptoms, it is easy for patients to overlook the condition and cause delays in treatment [3].

Vitamin D and Prostate Cancer: The Link Between Gene Expression and Cell Proliferation

The most widely recognized causes of prostate cancer are aging, family inheritance, and genes in different ethnic groups. Among them, the incidence of prostate cancer is highest among African American men. In addition, factors such as a diet high in saturated fats and dairy products, insufficient vegetable intake, lack of exercise, alcohol abuse, high blood sugar, environmental influences, and excess male hormones are also contributing factors to the development of prostate cancer [1]. For example, insufficient sunlight exposure can lead to vitamin D deficiency and increase the risk of cancer [3]. Vitamin D mainly circulates in the body in the form of 25-hydroxyvitamin D3 (25(OH)D3) bound to vitamin D-binding protein (DBP), and circulates throughout the body. DBP can transport vitamin D into cells and, upon entry into the cell, is catalyzed by an enzyme called 1α-OHase into the form of 1,25(OH)2D3. The 1,25(OH)2D3 form can then bind to the vitamin D receptor (VDR) in the cell nucleus. The resulting VDR-VDRE complex then binds to retinoic x receptors (RXR) to form a heterodimer. This heterodimer can then affect gene expression and transcription [7]. Therefore, various studies have shown that vitamin D3 gene expression can affect prostate cell proliferation, induce cell apoptosis and differentiation, and reduce cancer cell metastasis and invasion [3][7].

 (Figure 1) Mechanism of Vitamin D and Vitamin D receptor (VDR) in the prostate [7].

Prostate Cancer Treatment Options: Surgery, Radiation Therapy, Hormone Therapy, Chemotherapy, and Emerging Immunotherapy

Prostate cancer treatment options include surgical removal, androgen deprivation therapy (ADT), also known as hormone therapy, radiation therapy, stereotactic ablative radiation therapy (SABR), chemotherapy, and emerging immunotherapy. Surgery is usually the primary treatment for prostate cancer.

Radiation therapy

SABR is an early and low-risk cancer treatment method. Radiation therapy is used to replace surgical treatment and to control localized late-stage cancer or metastatic tumors that are not suitable for surgery [2].

Hormone therapy

ADT is commonly used for advanced cancer and tumor metastasis to other sites, known as metastatic prostate cancer. ADT includes testicular removal or the use of various anti-androgen drugs.

Chemotherapy

If the patient's drug therapy fails or the prostate tumor has recurrent and metastatic characteristics, the subsequent treatment will switch to chemotherapy [2].

Immunotherapy

Targeted treatment of the patient's immune system can be used for the treatment of metastatic tumors. FDA-approved therapeutic drugs include Docetaxel, Cabazitaxel, Abiraterone acetate, Enzalutamide, Sipuleucel-T, and Ra-223.

Ra-223 Special Treatment

It is a radioactive drug that emits alpha particles. The emitted alpha particle radiation will only target the damaged target area (such as bone cells) and cause DNA double-strand breaks within a 100 uM range, without any damage to surrounding tissues [6].

The latest trend in medication: FDA approves Orgovyx for oral treatment of prostate cancer.

In 2020, the FDA approved the first oral medication for the treatment of prostate cancer, called Orgovyx (relugolix). Orgovyx is specifically used for the treatment of advanced prostate cancer. It is a gonadotropin-releasing hormone (GnRH) receptor inhibitor. The epithelial cells of the prostate gland grow rapidly in response to stimulation by male hormones. Therefore, if the level of male hormones in the blood is reduced, tumor growth can be controlled. Orgovyx can competitively bind to the GnRH receptor, reducing the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which leads to the prevention of the release of the male hormone testosterone. The National Comprehensive Cancer Network (NCCN) guidelines consider GnRH inhibitors to have the same effect as orchidectomy surgery in preventing the release of male hormones, and the use of medication can avoid the physical and psychological discomfort associated with orchidectomy surgery [4]. Research also indicates that Orgovyx can lower testosterone levels more quickly than another GnRH inhibitor injection called Leuprolide acetate, and can reduce the risk of subsequent cardiovascular disease [5].

參考資料
1.Rawla P. (2019). Epidemiology of Prostate Cancer. World J Oncol.10(2):63-89. doi: 10.14740/wjon1191.
2.Evans, A. (2018). Treatment effects in prostate cancer. Mod Pathol .31: 110–121 doi: 10.1038/modpathol.2017.158.
3.Daniyal M, Siddiqui ZA, Akram M, Asif HM, Sultana S, Khan A. (2014). Epidemiology, etiology, diagnosis and treatment of prostate cancer. Asian Pac J Cancer Prev. 15(22):9575-8. doi: 10.7314/apjcp.2014.15.22.9575.
4.Cornford P, van den Bergh RCN, Briers E, Van den Broeck T et al..(2021). EAUEANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer. Part II-2020 Update: Treatment of Relapsing and Metastatic Prostate Cancer. European Urology. 79(2):263282. doi: 10.1016/j.eururo.2020.09.046.
5.Elliott, William; Chan, James. (2021).Internal Medicine Alert. Vol. 43:3.
6.Komura K, Sweeney CJ, Inamoto T, Ibuki N, Azuma H, Kantoff PW. (2018).Current treatment strategies for advanced prostate cancer. Int J Urol. 25(3):220-231. doi: 10.1111/iju.13512. 
7.Espinosa G, Esposito R, Kazzazi A, Djavan B.(2013).Vitamin D and benign prostatic hyperplasia -- a review. Can J Urol. 20(4):6820-5. PMID: 23930605.