Table of Contents

I. Introduction
• Definition of prostate cancer
• Location and function of prostate gland
• Prevalence of prostate cancer
II. Symptoms of Prostate Cancer
• Early stages
• Advanced stages
III. Diagnosis of Prostate Cancer
• Prostate biopsy
• Gleason grading scale
IV. Staging and Treatment of Prostate Cancer
• Treatment for early and advanced stages
• Radical prostatectomy
• 3D-conformal radiotherapy
• Cryotherapy, brachytherapy, and high intensity focused ultrasound
• Hormone blockade
• Chemotherapy
V. Conclusion and Prevention

Prostate cancer (PC) affects the prostate gland and is leading cause of cancer death in men over 50 years. The prostate is walnut-shaped gland located below the bladder. It produces fluid in semen that nourishes and transports sperm and also plays a role in urine control in men. If it is found in the early stages is also treatable. In the United States, it is the most common cancer in men 1 and in 2017, the American Cancer Society has predicted fresh cases of prostate cancer, leading to fatalities.

During the early stages of prostate cancer usually there are no symptoms. However, if symptoms appear, they usually involve – frequent urges to urinate, difficulty commencing and maintaining urination, blood in the urine, painful urination. Advanced PC include bone pain, renal failure, hematuria, pathological bone fractures, physical exhaustion, and weight loss. If cancer spreads to the spine and compresses the spinal cord, there may be leg weakness, urinary incontinence, fecal incontinence.

At present, PC diagnosis is made 5 to 10 years before symptoms appear. The most significant tools for PC diagnosis are prostate-specific antigen (PSA) levels (>4 ng/ml) and a suspicious digital rectal examination (DRE) (e.g., increased consistency or nodules). PSA screening due to its high sensitivity and low specificity lead to false positives. Up to 18% of PC cases are diagnosed by DRE as 5% of PCs do not show increased PSA levels. The PSA blood test has been used for the diagnosis and also as a useful marker for the PC monitoring. PSA screening has been found to show a progressive decrease in prostate cancer mortality 2. The prostate cancer gene 3 (PCA3) in urine has also been evaluated in screening 3. Prostate biopsy (BxP) is the current standard for the diagnosis of PC. A suspicious DRE and a PSA result higher than 4 ng/ml are the two main criteria for BxP. The objective of the biopsy is to obtain representative samples of the entire prostate gland for the pathologist to establish an accurate histological diagnosis. The most common prostate tumor is adenocarcinoma.

There is a special contribution by Donald Gleason of a grading scale which is fundamental for defining the stage and prognosis of PC patients. The scale is applied additively, with the first number representing the predominant histologic grade and the second number the secondary histologic grade. According to this reasoning, a Gleason value of 7 can reflect a 3+4 tumor (where 3 is the first number, i.e., less aggressive) or a 4+3 tumor (where 4 is the first number, i.e., more aggressive).

The stage of the disease plays a decisive role for both prognostic and therapeutic purposes. Treatment for PC is different for early and advanced stages. The cases with low and intermediate-risk PC with low tumor volume are actively monitored with PSA in blood and annual biopsies to determine disease progression. Radical prostatectomy (RP) as a treatment for PC has existed for over 100 years. In the case of radical prostatectomy the prostate is surgically removed. However, complications related to RP has led to the acceptance of other more conservative treatments. The National Comprehensive Cancer Network (NCCN) recommends a geriatric assessment in all patients over 65 with oncological disease to choose the therapy with the least physical impact and thus better quality of life for the patient 4. 3D-conformal radiotherapy (RT) has shown comparable results to RP without the immediate surgical morbidities. In conformal radiation therapy, radiation beams are shaped so that the region where they overlap is as close to the same shape as the organ or region that requires treatment. This minimizes healthy tissue exposure to radiation. In the advanced form of conformal radiation therapy, the Beams with variable intensity are used. The last 10 years have seen an increase in the use of new technologies for the surgical treatment of PC, such as laparoscopic and robotic techniques.

Among other modalities, cryotherapy, brachytherapy, and high intensity focused ultrasound (HIFU) have also been proposed for localized disease. The ultimate goal is to achieve tissue necrosis either from seeds of radioactive material (brachytherapy), freezing (cryotherapy) or ultrasonic waves (HIFU). Treatment recommendations depend on individual cases. The patient should discuss all available options with their urologist or oncologist. In the case of locally advanced disease therapies such as adjuvant or salvage radiation, monitoring or androgen deprivation can be offered. Hormone blockade is used as a palliative treatment in recurrent disease after radiation therapy. In the last decade, numerous studies have shown that hormone blockade, coupled with either of these therapies, can significantly increase the overall survival rate and decrease disease progression. However, castration is not without complications 4,5.

Disease in the metastatic stage is more aggressive and will have spread further throughout the body. Chemotherapy may be recommended, as it can kill cancer cells around the body. Androgen deprivation therapy (ADT), or androgen suppression therapy, is a hormone treatment that reduces the effect of androgen. Androgens are male hormones that can stimulate cancer growth. ADT can slow down and even stop cancer growth by reducing androgen levels. Hormone blockade is the preferred therapy for metastatic disease, though it is not a curative treatment. Its goal is the deprivation of androgen sources by surgical castration (orchiectomy) or by suppression or pharmacological castration (anti-androgens, similar inhibitors or GnRH agonists).

Prostate cancer is a slowly developing disease and early diagnosis with PSA screening has been beneficial. Overtreatment due to PSA is also a reality. The PSA test has high sensitivity but low specificity. PSA remains a valuable, although again imperfect, tool in the monitoring of men after treatment of the localized disease or with advanced prostate cancer. PC evolution based on PSA, the Gleason scale and DRE results help to predict but difficult to say that whether the PC will be indolent or aggressive. The patient must be involved throughout the examination with or without PSA and DRE, as well as in the selection of the most suitable treatment, ranging from observation to more radical treatments. The best therapeutic solution will be the one that provides survival with the best quality of life and can be supported by a multidisciplinary team. The development of novel diagnostic tests may allow a new, more rational approach to prostate cancer screening.

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