Prostate cancer is a malignant tumor that occurs in the male prostate tissue as a result of abnormal and uncontrolled growth of prostate alveolar cells. The incidence of prostate cancer has significant geographical and racial differences. In developed countries and regions such as Europe and the United States, it is the most common malignant tumor in men and its mortality rate ranks second among all kinds of cancers; in Asia, its incidence is lower than that in Western countries, but it has been on a rapid rise in recent years.
Disease Profile
The incidence rate of prostate cancer in genitourinary system malignant tumor in Shanghai in 2007 has jumped from the 3rd place to the first place, and has rapidly risen from the 9th place to the 5th place in the ranking of top 10 male tumors. It is predicted that in 10 years, the incidence of prostate cancer in Shanghai will be promoted to the top three among malignant tumors in men.
Early detection of prostate cancer requires universal prostate screening. The most easily recognized method for prostate cancer screening is a combination of rectal prostate examination and serum PSA testing, both of which play a very important role in screening. The vast majority of prostate cancers are detected by abnormal PSA, accounting for 80% of cases, while only 20% of cases are found to have nodal abnormalities on rectal examination. The frequency of prostate cancer screening should ideally be once a year. If progressive increases in PSA levels and/or abnormalities on rectal exam are found during annual screening, further testing is needed. With prostate cancer screening, the incidence of prostate cancer-related complications and prostate cancer-related mortality can be reduced, which can effectively improve survival rates. Usually men should start prostate cancer screening at the age of 50; or at the age of 40 if there is a family history of prostate cancer. [1][2]
Disease classification
More than 95% of prostate cancers are adenocarcinomas that occur in the prostate gland tissue and usually follow a certain sequence of progression: confined to the prostate gland -> invasion of the prostate envelope -> breach of the prostate envelope -> invasion of the seminal vesicle gland -> metastasis to adjacent regional lymph nodes -> metastasis to bones and other organs. Another important type of prostate cancer is neuroendocrine carcinoma or small cell undifferentiated carcinoma, which may originate from neuroendocrine cells rather than from the prostate gland. This type of prostate cancer usually metastasizes and spreads earlier, but does not secrete prostate-specific antigen (PSA) and is less susceptible to chemotherapy than conventional prostate cancer treatments. In addition, some less common malignancies can occur in the prostate, such as rhabdomyosarcoma, smooth muscle sarcoma, malignant nerve sheath (membrane) tumors, malignant mesenchymal tumors, and malignant tumors from other organs that metastasize to the prostate. Patients with these rare tumors generally have no significant increase in serum PSA values, and the tumors are generally large in size, often producing localized compression of adjacent organs, with most patients presenting with difficulty urinating and/or defecating. [1][3][4]
Pathogenesis
The exact etiology of prostate cancer is still unknown and may be related to genetic alterations. For example, alterations in androgen receptor-related genes lead to an increased risk of prostate cancer; men with the BRCA1 gene have three times the risk of prostate cancer than men without the BRCA1 gene; and abnormalities in the P53 gene are strongly associated with high-grade, highly aggressive prostate cancer. Genetic alterations may also be associated with environmental factors such as diet. The more genetic alterations there are, the greater the risk of prostate cancer. In a few cases, prostate cancer may be hereditary.
The risk factors associated with the development of prostate cancer have been summarized as follows
1. Absolute risk factors.
(1) Age: Age is the main risk factor for prostate cancer. Prostate cancer is very rare in men younger than 45 years old, but with increasing age, the incidence of prostate cancer increases dramatically, and the majority of prostate cancer patients are older than 65 years old. Basically, the incidence of prostate cancer almost doubles with each 10-year increase in age after 40 years, and the risk of prostate cancer in men aged 50-59 years is 10%, while the risk of prostate cancer in men aged 80-89 years increases steeply to 70%.
(2) Family history: When there is an immediate male relative in the family who has prostate cancer, the incidence rate of men in the family is significantly higher. Immediate male relatives generally refer to the father and brothers. If one immediate male relative has prostate cancer, the probability of developing prostate cancer is one time higher than in the general population; if there are two, it will be three times higher. This suggests that the development of prostate cancer may be related to a gene or a group of genes in the body, but these genes have not been fully identified by scientists to date.
(3) Ethnicity: The incidence of prostate cancer is highest in African Americans (i.e., black Americans), followed by Hispanics and Caucasians, while the incidence of prostate cancer in black Africans is the lowest in the world. The incidence of prostate cancer in Asian men living in the United States is lower than in Caucasians, but significantly higher than in native Asian men. Although the incidence of prostate cancer among yellow men has not yet reached the level of European and American countries, the incidence of prostate cancer in both China, Taiwan, Hong Kong, and Japan, Korea, and Singapore is showing a yearly increase.
(4) Abnormal cellular pathological changes in the prostate: Men with high-grade intraepithelial neoplasia of the prostate have a significantly higher incidence of prostate cancer. High-grade intraepithelial neoplasia is a precancerous lesion that shows abnormal cell growth patterns under the microscope, which is not cancerous, but often suggests the presence of prostate cancer, just not yet detected.
2. Relative risk factors.
(1) Diet: Some studies have shown that men who regularly consume foods containing high animal fats are also vulnerable to prostate cancer because these foods contain high levels of saturated fatty acids. The results of studies from 32 countries found that prostate cancer mortality was associated with total fat intake. In contrast, people who usually have a diet rich in vegetables and fruits are less likely to develop the disease.
(2) Androgen level: High androgen level in the body is also one of the possible causes of prostate cancer. Androgens can promote the growth of prostate cancer.
The increase in the prevalence of prostate cancer among Chinese residents is related to the aging of the population, improvement in living standards, changes in diet structure and environmental pollution. The results of the study showed that smoking, alcohol consumption, divorce or widowhood, and regular consumption of milk, eggs and pork are the main risk factors for prostate cancer in Chinese; while eating green vegetables, fruits and legumes are important protective factors. [3][5]
Clinical presentation
Because prostate cancer mostly originates in the peripheral zone of the prostate gland, it is insidious and grows slowly, so early prostate cancer may not have any premonitory symptoms, but only elevated serum PSA values and/or abnormal prostate changes on rectal examination. Once symptoms appear, it is often a more advanced progressive prostate cancer.
(1) If the tumor of the prostate is progressively enlarged and compresses the urethra of the prostate gland, it may cause urinary disturbance, which may manifest as progressive difficulty in urination (thinning of urine stream, skewed urine stream, bifurcation of urine stream, or prolonged urination), frequent urination, urgent urination, painful urination, incomplete urination, etc. In severe cases, urine dribbling and urinary retention may occur. These symptoms are similar to those of benign prostatic hyperplasia (BPH) and are easily misdiagnosed and missed, delaying early diagnosis and early treatment of the disease.
(2) For advanced progressive prostate cancer, symptoms such as fatigue, weight loss, and generalized pain may occur. As the pain seriously affects the diet, sleep and spirit, the systemic condition becomes weaker and weaker after long-term torment, wasting and weakness, progressive anemia, and finally the systemic failure and cachexia.
(3) When prostate cancer metastasizes to bone, it can cause bone pain at the metastatic site. Common sites of bone metastasis include the spine, hip, ribs and scapula. Bone pain occurs in about 60% of patients with advanced disease and is commonly found in the lumbar, sacral, hip and hip pelvis. Bone pain can manifest itself in different ways, with some patients presenting with persistent pain and others with intermittent pain. Bone pain may be confined to a specific part of the body or may manifest as wandering pain in different parts of the body; it may vary at different times of the day and respond differently to rest and activity. If the bone is significantly brittle due to tumor invasion, pathological fractures are likely to occur. Certain areas are common sites of arthritis, such as the knee and shoulder joints. Pain in these areas is not necessarily due to prostate cancer metastasis and further testing is needed to clarify the presence of prostate cancer metastasis.
(4) In 1/2 to 2/3 of patients, lymph node metastases are present at the time of initial presentation, mostly in the internal iliac, external iliac, retroperitoneal, inguinal, mediastinal, and supraclavicular areas. If prostate cancer metastasizes to adjacent regional lymph nodes, there are usually no symptoms. In rare cases, when the lymph nodes metastasize extensively and the lymph nodes swell significantly, compressing the blood vessels and blocking the lymphatic return to the lower extremities, the symptoms of swelling of the lower extremities and scrotum will appear.
(5) Advanced prostate cancer with spinal metastasis, if the spine is fractured or the tumor invades the spinal cord, it can lead to nerve compression, which in turn can cause paralysis and requires immediate emergency hospital treatment.
(6) If prostate cancer invades the base of the bladder or has extensive metastases in the pelvic lymph nodes, unilateral or bilateral ureteral (the channel that drains urine from the kidneys to the bladder) obstruction may occur. Signs and symptoms of ureteral obstruction include oliguria (or anuria in the case of bilateral ureteral obstruction), low back pain, nausea, vomiting, and fever in the case of co-infection.
(7) Prostate cancer is usually not associated with hematuria and hematospermia; however, if hematuria and hematospermia occur, you should go to the urology clinic for relevant tests to exclude the possibility of prostate or seminal vesicle gland tumors.
(8) Patients with extensive metastatic prostate cancer may experience bleeding from ruptured tumors. In addition, patients with prostate cancer may develop anemia. The cause of anemia may be related to tumor bone metastasis, endocrine therapy, or the duration of the disease. Patients may not have any symptoms of anemia because blood cell counts generally show a slow decline. Some patients with severe anemia may experience weakness, postural hypotension, dizziness, shortness of breath, and a feeling of fatigue. [1][5]
Differential diagnosis
Ancillary tests
Pathological examination of prostate puncture biopsy tissue is currently the gold standard for confirming the diagnosis of prostate cancer. The only effective and accurate means of diagnosing tumors is pathological diagnosis, and prostate cancer is no exception. The so-called pathological diagnosis is to determine the final diagnosis of the tumor by removing the tumor completely or cutting a part of the tumor tissue, and after many steps of processing, the pathologist will analyze the morphology and other intrinsic characteristics of the tissue cells through microscopic observation.
The main other examinations are: ECT bone scan, chest X-ray, internal organ ultrasound, pelvic MRI or CT, etc. The purpose of these examinations is to make a comprehensive assessment of the disease, to determine whether the disease is early or advanced, and whether the tumor is confined to the prostate or has metastasized to distant organs or lymph nodes. For example, chest X-ray can observe whether there are lung metastases; internal ultrasound can observe whether there are metastases in the liver, spleen, kidneys and other important organs; ECT bone scan is more important to identify whether there are bone metastases; pelvic MRI or pelvic CT can determine whether there are enlarged pelvic lymph nodes; and MRI can further observe whether there is localized outward invasion of the prostate to the seminal vesicle gland, rectum and bladder neck. The results of these examinations play a decisive role in the choice of the patient’s treatment plan.
Differential diagnosis
1. Prostate hyperplasia: Prostate cancer should be differentiated from prostate hyperplasia. Prostate enlargement and prostate cancer are two different diseases, although both occur in the prostate, but in general, prostate enlargement itself will not turn into prostate cancer. If you compare the prostate gland to an egg, then the envelope of the prostate is the eggshell, the peripheral zone of the prostate is the protein, and the migrating zone of the prostate is the yolk in the center. The prostate enlargement occurs mainly in the central region of the prostate in the migratory zone, while prostate cancer occurs mainly in the peripheral zone of the prostate, and there is a big difference in the anatomical location of the two. In addition, prostatic hyperplasia and prostate cancer are two completely different pathological processes. To date, there is only evidence that androgens can contribute to the transformation of pathological prostate cancer to clinical prostate cancer, and there is no evidence to contribute to the transformation of benign prostatic hyperplasia to prostate cancer. However, prostate enlargement and prostate cancer can co-exist, never assume that with benign prostate enlargement no cancer will grow, also a small percentage of prostate cancer (about 10%) will occur in the prostate migratory zone, so sometimes prostate cancer can be found in specimens after prostate enlargement surgery. The actual fact is that you can find a lot of people who are not able to get a good deal on this kind of things.
2. Prostatitis: Generally speaking, prostatitis belongs to the category of inflammation and is not directly related to prostate cancer. The most common cause of prostatitis is in young and middle-aged men, while prostate cancer is mostly seen in older men. Prostatitis can be accompanied by fever and painful burning urination during acute attacks, and can also cause a temporary increase in serum PSA, but these inflammatory symptoms usually subside quickly after anti-inflammatory treatment, and PSA can drop rapidly to normal levels within a short period of time. Many of the triggers that lead to prostatitis, such as alcohol consumption and a spicy diet, are not conducive to prostate cancer prevention, so abstaining from these bad habits and dietary habits can be very beneficial in maintaining a healthy prostate. [3][5]
Treatment of the disease
There are several treatments for prostate cancer, each of which has its own advantages and disadvantages. Depending on the purpose of treatment, prostate cancer treatments are divided into curative and palliative treatments. Palliative treatments are those aimed at delaying tumor progression and relieving tumor-related symptoms.
Surgical treatment
Surgery is the most commonly used curative treatment, called radical prostate cancer surgery, to remove the prostate and tumor intact. Radical prostate cancer surgery can be performed by the retropubic route (incision from the umbilicus to the upper border of the pubic bone), the trans-perineal route (incision between the scrotum and anus) and laparoscopic or robot-assisted radical prostate cancer surgery. The appropriate surgical approach is chosen according to the patient’s body type and disease characteristics, as well as the surgeon’s technical expertise.
Other treatments
1.Extracorporeal EBRT: It is a new method of applying external radiation therapy to prostate cancer. By increasing the maximum dose of radiation to the prostate area and reducing the dose to the surrounding prostate tissue, it can reduce the adverse effects of traditional external radiation therapy and improve the treatment effect.
2.Radioactive particle implantation therapy (brachytherapy): Radioactive particles are implanted into the prostate through the skin of the perineum to kill prostate cancer by brachytherapy, which is one of the curative treatments for prostate cancer because of the small damage and usually does not require other treatment aids. According to the grading, stage and PSA value of the tumor, after the radioactive particle implantation treatment, it can be further treated with extracorporeal moderate radiation therapy.
Cryotherapy: It is a minimally invasive treatment, in which a probe is placed into the prostate through the perineal skin under ultrasound guidance, and then liquid nitrogen at -96 degrees Celsius is injected into the probe to freeze and kill the tumor cells. Currently, cryotherapy is often used as a second-line treatment for prostate cancer patients who have failed after external irradiation treatment.
4. High-energy focused ultrasound therapy and radiofrequency ablation of intra-tissue tumors: also a local treatment method that is still in the experimental stage. Compared with radical prostate cancer surgery and radiotherapy, their therapeutic effects on clinically limited prostate cancer are not well established and need to be evaluated in more clinical studies.
5.Endocrine therapy for prostate cancer: It is a kind of palliative treatment, including medication, injection, medication combined with injection, and bilateral orchiectomy. By removing or blocking the effect of testosterone (i.e. androgens) on prostate cancer cells to temporarily inhibit the growth of prostate cancer cells and slow down the progression of the disease.
6. Chemotherapy: It is used to treat patients with metastatic prostate cancer who are resistant to endocrine therapy in order to slow down the growth of the tumor and prolong the life of the patient. Studies have confirmed that docetaxel is effective in extending the survival time of patients with endocrine therapy-resistant prostate cancer; and cabazitaxel can further extend the survival time of those patients who have failed docetaxel treatment. Many clinical trials are investigating new drugs and drug combinations with the goal of finding more effective treatments with fewer adverse effects. Abiraterone is one of the most clinically useful new drugs, with a high efficiency for endocrine therapy-resistant prostate cancer.
7.Nucleotide therapy: It is a palliative treatment for patients with bone pain from prostate cancer bone metastases. Intravenous or oral diphosphonates can also be used to treat bone pain caused by bone metastases.
8. Other treatments: other treatments such as biologically targeted therapy are still in clinical trials. [1][4][5]
Disease prognosis
Stage A: 8-20% chance of distant metastases, 5-year survival rate 90-95%%.
Stage B: 30-40% metastasis within 5 years, with a 5-year survival rate of 60-70%.
Stage C: 50% distant metastases within 5 years, with a 5-year survival rate of 30-40%.
Stage D: 20% survival rate at 5 years, less than 10% survival rate at 10 years
Disease Prevention
Many dietary factors can increase the risk of developing prostate cancer. Several studies have shown that a high-fat diet can stimulate prostate cancer growth. Beef and high-fat dairy products appear to be stimulants for prostate cancer, and high dairy intake can increase the risk of prostate cancer; conversely, fruits and vegetables and a low-fat diet may help reduce the risk of prostate cancer. These healthy foods include soy (tofu and soy milk), tomatoes, pomegranates, green tea, red grapes, strawberries, blueberries, peas, watermelon, rosemary, garlic, and citrus.
Soy contains phytoestrogens, similar to estrogen in women. Phytoestrogens in dietary dose conditions (the dose contained in normal foods, not supplemental doses) can reduce the risk of prostate cancer.
Green tea contains a variety of antioxidants, with the main components at play being tea polyphenols and catechins compounds. The antioxidant components of green tea have a significant inhibitory effect on the malignant transformation of cells induced by a variety of carcinogens, including aflatoxins, benzo(a)pyrene, cigarette carcinogens, and amino acid cleavage products, helping to stabilize cell structure and reduce cell damage, which can cause cellular carcinogenesis.
Many fish such as salmon, tuna, sardines and herring are rich in Omega 3 fatty acids, which have both cardiovascular disease and cancer prevention effects.
Minerals play a very important role in the growth and normal functioning of the human body. There are more than 60 minerals in the human body, 22 of which are essential minerals that the body cannot synthesize on its own, which means they must be obtained from food or supplements. Selenium is an important antioxidant, and scientists have found that it has anti-cancer effects and can reduce the incidence of prostate cancer by up to 70%, so it can be consumed in appropriate amounts. Dietary selenium is mainly found in foods such as animal liver, seafood, whole grains, milk and dairy products, mushrooms, garlic and asparagus, and the amount of cancer prevention is 100 to 200 micrograms per day intake. White melon seeds contain essential zinc, which helps the body repair wounds, promotes cell regeneration and fights free radicals. The intake of zinc for adults is 15 mg per day. The body’s immunity decreases when zinc is deficient, although there is no positive evidence that zinc can reduce the incidence of prostate cancer.
Recent studies have found that the popular crimson pomegranate juice also has an anti-prostate cancer effect. Researchers in the United States injected human prostate cancer cells into rats to give them prostate cancer and then gave them pomegranate juice to drink. After a period of “food therapy”, they found that the tumors shrank. Pomegranate juice is rich in antioxidants, the chemicals that give fruits and vegetables their darker color, and it can counteract damage to cells that can then develop into cancer or other diseases. A recent study showed that drinking a glass of pomegranate juice a day significantly slowed the growth of malignant tumors in prostate cancer patients. Prostate cancer patients who were asked to drink one glass of pomegranate juice (225 ml) a day had significantly slower progression – their PSA levels only increased by a factor of one after 54 months. The use of pomegranate juice for adjuvant therapy was not only effective, but also produced no other adverse effects.
Disease care
(1) Maintain an appropriate body weight and keep the body mass index (BMI) less than 30, BMI = weight (kg)/height2 (m2).
(2) Adhere to physical exercise, and the amount of exercise should be appropriate.
(3) Choose a plant-based diet.
(4) Do not smoke and do not abuse alcohol.
(5) Limit the intake of fat to no more than 20% of total calorie intake.
(6) Do not eat junk food and avoid saturated fats in your diet as much as possible.
(7) Eat more fish as it is rich in certain beneficial fatty acids.
(8) Eat 7 to 9 meals a day of fruits and vegetables and limit the intake of sugar and salt to prevent cancer and maintain a healthy heart.
(9) Consume more fiber-rich foods, at least 30 grams per day.
(10) Consume soy products once or twice a day, which can be low-fat soy milk, tofu, soy protein powder, etc.
(11) Take adequate doses of calcium and vitamin D to prevent osteoporosis.
Physical activity plays a very important role in weight control, muscle preservation, keeping bones strong and reducing the incidence of heart disease. Consistent physical activity also helps maintain good balance in the body, promotes sleep and reduces anxiety. Through physical activity, you can also lose excess fat. Strength training (e.g. cycling, weight-bearing exercises, etc.) helps patients increase muscle mass and helps improve the ability to burn energy at rest; it also promotes bone health and improves balance, which helps reduce the incidence of falls and fractures. Aerobic training, which includes brisk walking, dancing, hiking, swimming and jogging, burns energy while exercising and continues to burn fat and expend energy for hours after the exercise is over. In addition, a healthy body gives the patient a better immune system, which is an important capital to beat prostate cancer. Light regular physical activity includes dancing, brisk walking to and from work, and cleaning the house. Moderate physical activity includes playing badminton for 30 minutes, basketball for 15 to 20 minutes, swimming for 20 minutes, paddling for 30 minutes, or running 2 kilometers in 15 minutes. The maximum amount of exercise varies for each person and try not to exceed a moderate intensity workout. Most experts recommend exercising at least three to four times a week for 30 minutes each time, with an exercise intensity of 60 to 70 percent of one’s maximum physical strength. Regardless of the type of exercise chosen, it is important to be consistent in order to obtain long-term benefits.