Metastatic Prostate Cancer

Summary
Prostate cancer is a common malignant tumor of male urinary system and the most prevalent male cancer in United States1. As the wester life style is getting more common in China, the incidence and morality of prostate cancer has picked up in the last decade2.
Prostate cancer, known as carcinoma of the prostate, is the development of cancer in the prostate a gland in the male reproductive system, most prostate cancers are slow growing; however, some grow relatively quickly. The cancer cells may spread from the prostate to other parts of the body, particularly the bones and lymph nodes. Once the tumor cells migrate to bone and / or lymph node beyond pelvic, the disease turns into metastatic prostate cancer. High risk metastatic hormonal sensitive prostate cancer (mHSPC) and metastatic castration resistant prostate cancer (mCRPC) are difficult to treat thus attract clinician’s more interests. mHSPC denotes the metastatic prostate cancer cells have response to androgen deprivation therapy (ADT). Once the patients have radiological or biochemical progression against castration, the disease will develop to mCRPC stage.
Causes

Prostate cancer is driven by the activation of androgen – androgen receptor pathway3. Men who have first-degree family members with prostate cancer appear to have double the risk of getting the disease compared to men without prostate cancer in the family.

Symptions
  • Early prostate cancer usually has no clear symptoms. Sometimes, however, prostate cancer does cause symptoms, often similar to those of diseases such as benign prostatic hyperplasia.  include frequent urination, difficulty starting and maintaining a steady stream of urine, hematuria(blood in the urine), and dysuria(painful urination).
  • Prostate cancer is associated with urinary dysfunction as the prostate gland surrounds the prostatic urethra. Changes within the gland, therefore, directly affect urinary function. Because the vas deferens deposits seminal fluid into the prostatic urethra, and secretions from the prostate gland itself are included in semen content, prostate cancer may also cause problems with sexual function and performance, such as difficulty achieving erection or painful ejaculation.
  • Advanced prostate cancer can spread to other parts of the body, possibly causing additional symptoms. The most common symptom is bone pain, often in the vertebrae (bones of the spine), pelvis, or ribs. Spread of cancer into other bones such as the femur is usually to the proximal or nearby part of the bone. Prostate cancer in the spine can also compress the spinal cord, causing tingling, leg weakness and urinary and fecal incontinence. 
Treatment
  • Many men diagnosed with low-risk prostate cancer are eligible for active surveillance. This term implies careful observation of the tumor over time, with the intention of treatment for cure if there are signs of cancer progression. Active surveillance is not synonymous with watchful waiting.an older term which implies no treatment or specific program of monitoring, with the assumption that palliative, not curative, treatment would be used if advanced, symptomatic disease develops. Treatment of aggressive prostate cancers may involve surgery (i.e. radical prostatectomy), radiation therapy including brachytherapy (prostate brachytherapy) and external beam radiation therapy, high-intensity focused ultrasound (HIFU), chemotherapy, hormonal therapy.
  • mHSPC should be mainly treated by hormonal therapy, namely castration therapy, which includes medication and surgical castration. LHRHa is the most widely used castration treatment, which surgical castration is rarely used in China. For the high risk mHSPC patients, current standard cares are abiraterone prednisone plus castration or docetaxel plus castration.
  • Most mHSPC patients become mCRPC finally. Before 2004, no treatment proved to prolong the survival. However, there are now several treatments available to treat mCRPC that improve survival, abiraterone is one of them. current standard cares are abiraterone prednisone plus castration or docetaxel plus castration8. Bone targeted therapies could prevent skeleton related events, relieve bone pain and improve quality of life.

1.  Siegel, R.L., et al. Cancer Statistics, 2017. CA Cancer J Clin, 2017. 67(1):7-30.
2.  Chen, W., et al., Cancer statistics in China, 2015. CA Cancer J Clin, 2016. 66(2):115-32.
3.  Tan MH et al. Androgen receptor: structure, role in prostate cancer and drug discovery.Acta Pharmacol Sin. 2015 Jan;36(1):3-23.
4.  Fizazi, K., et al., Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med, 2017.2017 Jul 27;377(4):352-360.
5.  2017 European Association of Urology, Updated Guidelines for mHSPC AAP+ADT is Another Standard.
6.  Sweeney C J , Chen Y H , Carducci M , et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med, 2015.373(8):737-46.
7.  Sun, Y., et al., Abiraterone acetate for metastatic castration-resistant prostate cancer after docetaxel failure: A randomized, double-blind, placebo-controlled phase 3 bridging study. Int J Urol, 2016.23(5):404-11.
8.  Ye, D., et al., A phase 3, double-blind, randomized placebo-controlled efficacy and safety study of abiraterone acetate in chemotherapy-naïve patients with mCRPC in China, Malaysia, Thailand and Russia. Asian J Urol, 2017.4(2):75-85.
9.  Petrylak DP, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004;351:1513-1520.

CP-87251 Approved date 2019-5-6