Prostate Cancer in the Elderly
Introduction
Introduction to prostate cancer in the elderly Prostate cancer in the elderly is a malignant tumor originating from the prostate and is a common malignant tumor of the male genitourinary system. Among the malignant tumors of all organs, the natural history of prostate cancer varies widely, and it varies from person to person and is difficult to predict. basic knowledge The proportion of illness: the incidence rate is about 0.005% - 0.009% Susceptible people: the elderly Mode of infection: non-infectious Complications: hematuria anemia
Cause
The cause of prostate cancer in the elderly
Androgen levels (30%):
The cause of prostate cancer is unknown. Although prostate cancer does not occur in castrated people, there is almost no prostate cancer in children with testicular dysplasia. Prostate cancer can be significantly reduced after testicular excision. However, there is no objective data to prove that androgen levels and prostate cancer in vivo. There is also no evidence that there is a causal relationship between prostate hyperplasia and prostate cancer.
Other (20%):
Excessive sexual life, repeated infection of the prostate or chronic inflammation, smoking, industrial carcinogen cadmium and other etiological hypotheses, can not explain the high incidence in Europe and the United States and the low incidence in Asia and the disparity in the incidence of different races and regions.
Cytogenetic damage (30%):
In recent years, more and more studies have shown that the genetic damage of cells plays an important role in the pathogenesis of prostate cancer. Environmental factors such as radiation, chemical substances, physical damage caused by DNA mutations or other types of abnormalities, namely, primary cancer Activation of genes such as Ha-ras, C-erbB-2, myc and loss or mutation of tumor suppressor genes such as P53 can cause carcinogenesis in sensitive cells.
Pathogenesis
The classification of prostate malignant tumors can be divided into: cell type and origin: 1 originated from the epithelium with adenocarcinoma, transitional cell carcinoma and neuroendocrine carcinoma; 2 originated from mesenchymal (stroma) with rhabdomyosarcoma and leiomyosarcoma; Carcinoma can be directly caused by bladder cancer or colon cancer, and can also be metastasis (such as lung cancer, melanoma), lymphoma is rare, adenocarcinoma accounts for 95% of all malignant tumors, and 90% of the remaining part is transitional cell carcinoma. .
1. The anatomical part of the origin of adenocarcinoma can be divided into the central zone, the peripheral zone and two sub-regions, namely the transition zone and the urethra zone, close to the proximal section of the prostate urethra. Most of the prostate cancer originates from the transition zone, ie In the so-called "outer prostate", the outer gland has two different sets of tubes, which are divided into two distinct areas in histology and biology:
1 outer circumference belt;
2 Central zone, prostate cancer originates from the central zone only 5% to 10%, the tumor located at the base of the prostate is not uncommon here, more than half of the cancer originates from the peripheral zone, and the peripheral zone accounts for the normal prostate gland. 70%, the rectal examination is easy to touch the tumor, and the anterior lateral wing of the peripheral zone is also like the transitional zone. It is only expected to be accessible when the tumor is quite large. The transitional mass is often closely related to benign prostatic hyperplasia. It is not easy to determine the susceptibility to cancer. It is estimated that 20% of adenocarcinomas originate from this site. The literature reports that anterior medial prostate cancer or transitional cancer exists in the area where BPH occurs, usually found in the removal of proliferating glands, clinically Occasional cancer (TA stage).
2. Pioneer lesions
Precancerous lesions are best determined by long-term observation of suspicious lesions, such as body surface and cavity, until infiltration occurs, but the prostate is a substantial organ, and the above-mentioned methods cannot be used to determine precancerous lesions, accompanied by prostate cancer. The two proliferative lesions that occur are considered to be cancer precursor lesions:
(1) adenosis (adenosis): is a kind of "atypical adenomatoid hyperplasia" or "adenomatosis" similar to glandular prostatic hyperplasia nodules, glandular cells are high columnar, cytoplasm is normal pale, just The enlargement and abnormality of the nucleus are not constant, and other lesions show uneven glandular size, which is singular in large glands.
(2) duct-acinar dysplasia: Many scholars such as Andrews and McNeal describe another precancerous lesion characterized by cell proliferation in pre-existing tube-gland units and adenoma disease. Usually there are no abnormal cells and nuclear abnormalities, "tube-glandular dysplasia" is also known as "prostatic intraepithelial neoplasia", dysplasia is often a small lesion with obvious boundaries, epithelial staining, in the absence of cancer Intra-prostate lesions rarely exceed 4 mm, but are common in cancerous prostates, especially near tumor infiltrates, usually suggesting a transitional phase of invasive cancer.
3. Histological characteristics
The small prostate cancer that can be detected clinically has at least moderate histology. McNeal reports that the prostate cancer volume found by autopsy is about 70% smaller than 1ml, and such small tumors are the most common prostate cancer patients in the population. On the contrary, on the contrary, about 80% of the patients with prostate cancer are more than 1ml in volume. The biological relationship between autopsy and clinical cancer is still controversial. The time of cancer may be the factor, about half of the clinical cancer. The undetected cancer in the prostate is multifocal. The shape of the prostate cancer cells is pleomorphic. The degree of cell differentiation is usually not used as a basis for classification. Immunohistochemical examination uses PSA and PAP as markers, according to its staining. Depth can be used to distinguish high, medium or poor differentiation of cancer cells, but in well-differentiated cancers, the staining tends to vary in depth, and the classification according to the depth of staining is not very reliable.
The cytoplasm of infiltrating prostate cancer is more deeply stained and loses the numerous small vacuoles contained in normal cells. The highly differentiated cancer cells can store transparent, pale diffuse vacuoles, so-called "clear cell cancer". For Gleasonl and Grade 2, it almost all originated in the transition zone, and such patients have a better prognosis.
The nucleus of prostate cancer has almost increased in degree, but it is only partially found in cells of well-differentiated cancer. Nuclear enlargement is often accompanied by deepening of staining and enlargement of nucleoli.
4. Structure type
The only type of tissue that can express tumor histology is the type of prostate cancer. These types are ranked according to the process of non-differentiation to estimate the prognosis and guide treatment. Among all the classification methods, two are more commonly used:
(1) Mostofi grading system The Mostofi system is divided into three levels, considering both gland structure and cytological characteristics. Grade I: good gland differentiation, slight nuclear deformation; grade II: gland structure exists, but nuclear moderate Change; Grade III: glands with significant nuclear deformation and undifferentiated tumor tissue, this classification is simpler but not perfect.
(2) Gleason grading system Gleason grades according to the gland morphology seen under low magnification, and the main structure (primary) and secondary structure (secondary) with dominant tumor morphology from differentiation to differentiation The worst is divided into 5 levels:
Grade 1: Tumors consist of structures that are homogeneous, single, separate, dense and bordered.
Level 2: Although the tumor has borders, a small number of tumor glands invade the adjacent non-tumor glands. The glands are still single and separated, but the arrangement is loose, not as uniform as level 1.
Grade 3: The tumor infiltrates into the normal prostate, the size and shape of the gland are different, and the sieving cancer nodules with smooth edges are also grade 3.
Grade 4: The glands are not single, separated, but merged with each other and the edges are not neat.
Level 5: The tumor does not differentiate into glands, is a solid cell mass, scattered cells infiltrate or nest with cancer cells with central necrosis.
Prevention
Elderly prostate cancer prevention
Third-level prevention
Primary prevention: also known as etiological prevention. It is an effective preventive measure for the causes and risk factors of malignant tumors. Since the 1940s, dietary and nutritional factors have become the focus of inducing tumors and reducing high fat. Diet, moderate intake of vitamin A, C, E and cellulosic foods will reduce the incidence of prostate cancer. Chemoprevention was initiated by Dr. Michael, Sporn in the mid-1970s. The definition of chemoprevention is to use The natural or synthetic compound is used to prevent the invasive cancer by reversing or inhibiting the cancer in its preclinical or early stage. Finasteride is a 5 reductase inhibitor that blocks the testosterone from being reversed to active. The metabolite dihydrotestosterone, which plays a very important role in the development of prostate cancer, has been an unprecedented clinical phase III trial in the United States by the Prostate Cancer Prevention Experimental Group (PCPT). The association conducted a one-year follow-up study on dietary intake and found that tomato-based foods and strawberries were The main source of pigment (a non-original vitamin A carotenoid that has antioxidant effects), it can reduce the risk of prostate cancer, with more than 10 times of tomato products per week, and less than 1.5 times In contrast, the risk of prostate cancer is inversely proportional. Selenium is an essential non-metallic trace element with anti-oxidant and anti-proliferative properties. It can induce apoptosis and promote differentiation. Clark et al. The role of selenium has been experimentally studied, and the incidence of prostate cancer can be reduced by follow-up observation.
Secondary prevention: Due to the long preclinical period of prostate cancer, the incidence of men over 50 years old is very high. It is necessary to carry out a general screening of prostate cancer. There are three kinds of census methods: physical examination, that is, rectal anal examination - DRE Serological examination, which is to determine the level of serum prostate specific antigen - PSA; imaging diagnosis, that is, transrectal ultrasound - TRUS, the American Cancer Society prostate cancer screening research program data shows that the sensitivity of DRE is 50% The specificity is 94%. It is suggested that men over 50 years old or with high risk factors should do DRE every year. Unlike carcinoembryonic antigen, PSA is only produced by prostate. The higher the level of PSA, the more it is for prostate cancer. Specificity, PSA levels greater than 10 ng / ml, its specificity exceeds 90%, such as the combination of PSA and DRE, will be better than either method alone.
Tertiary prevention: After the diagnosis of the disease, according to the clinical stage of the elderly cancer patients, physical status, and taking into account whether the patient's actual life expectancy is longer than the natural life expectancy of the tumor patients, take effective comprehensive treatment to prolong the survival period, The palliative treatment of advanced patients relieves pain and improves the quality of life of patients.
2. Risk factors and interventions
Many scholars have studied the risk factors associated with prostate cancer, and have not yet reached a definitive conclusion. It is generally believed that prostate cancer occurs more frequently in men with more sexual life and more fertility, but only a few statistically significant differences have been reported. Herpes Viral type II, Simian virus and cytomegalovirus were once thought to be carcinogenic factors. These are pathogens of sexually transmitted infections, but cervical cancer is rarely seen in spouses of prostate cancer patients. Occupational and environmental studies suggest that cadmium and zinc may It is a chemical carcinogen of this disease, but it has not yet reached a conclusion. Studies on diet suggest that excessive consumption of fat is positively correlated with the incidence of prostate cancer. A Japanese report suggests that more green and yellow vegetables can reduce the incidence of prostate cancer. The degree survey found that the incidence of primary education is high, low by university educators, high incidence of early marriage, low late marriage; high incidence of family history of prostate cancer, may be related to genetic susceptibility and the same living environment; More boys, for the risk factors, advocate late marriage, less education, pay attention to reproductive organs and appropriate Sex life, can reduce the incidence of prostate cancer in elderly patients.
3. Community intervention
According to the epidemiology of prostate cancer, prostate cancer in the elderly has an increasing trend year by year. Tumor is becoming a growing social problem. It is one of the major medical burdens in the modern era. In order to achieve early diagnosis and early treatment, many countries have The census of prostate cancer has been carried out. Community health stations are obliged to carry out census work for high-risk groups. Older men conduct annual census work, do a good job in anti-cancer publicity work, and provide nursing guidance and treatment for patients during rehabilitation.
Complication
Elderly prostate cancer complications Complications, hematuria anemia
The main complications are hematuria, anemia, and bone metastases.
Symptom
Prostate cancer symptoms in the elderly Common symptoms Prostatic hyperplasia Male abdominal pain Prostate hard knot Urinary frequency Blood urinary flow Slow urinary incontinence Urinary urgency interrupted without urine
Clinical symptoms
Early prostate cancer is often asymptomatic. When the tumor enlarges to block the urinary tract, there is a similar phenomenon of bladder neck obstruction similar to benign prostatic hyperplasia. There is a gradual increase in urinary flow, frequent urination, urgency, interruption of urinary flow, and urination. Urinary dysfunction and even urinary incontinence, hematuria is not common, late low back pain, leg pain (neural compression), anemia (broad bone metastasis), lower extremity edema (lymphatic, venous return obstruction), bone pain, pathological fracture, paraplegia (bone Metastasis), dysuria (rectal compression), oliguria, anuria, uremia symptoms (bilateral ureteral compression), some patients seek medical attention with metastatic symptoms, without primary prostate symptoms.
2. Digital rectal examination
Rectal examination is the primary diagnostic procedure. Check the size, shape, presence or absence of irregular nodules, size of the mass, hardness, extent of expansion and seminal vesicles during the examination. The prostate enlarges, hard, nodules, during routine physical examination. The surface is uneven, the central sulcus disappears, the gland is fixed or invaded the rectum, and the tumor originating in the transition zone can be reached when it is increased to a certain extent. The tumor is often hard as a stone, but the difference is large, the infiltration is extensive, and the variability occurs. The lesion may be soft, and the prostate rectal examination associated with benign prostatic hyperplasia is sometimes difficult to distinguish. The differential diagnosis of prostatic induration is granulomatous prostatitis, prostatic calculus, prostate tuberculosis, non-specific prostatitis and nodular prostatic hyperplasia. Care should be taken to identify it.
Examine
Elderly prostate cancer screening
PSA is the most important prostate cancer marker, prostatic acid phosphatase sensitivity is poor, alkaline phosphatase increased should pay attention to whether there is extensive bone metastasis, advanced prostate cancer compression bilateral ureter can cause serum creatinine, increased urea nitrogen and CO2 The bonding force is reduced.
1. Prostatic acid phosphatase (PAP)
Serum acid phosphatase has been used as a marker for prostate cancer for 40 years. Due to the lack of specificity of acid phosphatase and poor stability of enzyme at room temperature, there are biological variations in enzymes within 24 hours. The significance of abnormal enzyme increase is difficult to determine. In addition to prostate cancer, many other organs and tissues can cause acid phosphatase increase, so its practical value is very affected. In 1974, Cooper et al first used radioimmunoassay to measure serum prostatic acid phosphatase (PAP), making it sensitive. Sexuality and specificity were significantly improved. Li Quanlin et al reported a group of cases using the PAP radioimmunoassay kit produced by Jiangsu Atomic Energy Research Institute for routine radioimmunoassay. The normal value of male adults was <2.5 g/L, and the PAP level of 30 patients with prostate cancer was 4.18+3.33g/L (0.1513.64g/L), in which PAP is higher than normal, accounting for 63.3%, PAP increasing rate is 0 in stage A, 44.4% in stage B, 75% in stage C, and 81.8% in stage D. PAP was measured by biochemical enzymatic analysis in 30 patients. Only 26.7% of patients were higher than normal. The sensitivity was much lower than that of radioimmunoassay. The increase of PAP in patients with benign prostatic hyperplasia was below 3.0g/L. Foreign data also indicated that PAP was not Rational Markers, since serum prostate-specific antigen test later used in clinical scholars have replaced the PAP detected by PSA, in order to save money.
Prostate specific antigen
Prostate specific antigen (PSA) is an enzyme produced only by the prostate epithelium. It is a glycoprotein that hydrolyzes the clot of semen. Its function is related to male fertility. PSA has a molecular weight of about 30,000 and contains 240 amino acids. And 7% carbohydrate, which is similar to the protease of the kallikrein family. It is present in blood and seminal plasma. PSA is a more sensitive marker than PAP, but it is specific for the screening diagnosis of prostate cancer. Sexuality is still not high, serum PSA can be increased in patients with prostate cancer and benign prostatic hyperplasia (BPH). It is an important marker for monitoring the prognosis of prostate cancer. According to domestic literature, the upper limit of serum PSA is normal: the enzyme release method (EIA) is 3.6. Gg/ml, radioimmunoassay (EIA) is 2.8 or 3.0g/ml. The normal values of the kits produced by different companies are slightly different. China has been able to prepare PSA monoclonal antibodies with high specificity and high titer, and clinically PSA ( Radioimmunoassay) >3g/ml is suspicious, PSA increase in BPH patients is not significant, about 0.3g/ml/gBPH, PSA increase in prostate cancer patients is proportional to the volume of intracapsular cancer, except for a few reported A1 patients abroad, domestic reports A small number of patients with stage A and B PSA can be Outside the normal range, all stages of prostate cancer were higher than normal, PSA <10g / ml more than metastasis, >50g / ml more extensive infiltration and metastasis, severe cases can be as high as 500g / ml or more, a few exceptions are D2 Tumor-caused cancer cells lost their ability to differentiate. PSA histochemical examination showed that the staining was very light. In this case, the tissue-secreted PSA was reduced, and only the PSA value of the patients in the second phase was normal before treatment.
Serum PSA levels are fairly stable, and there is no significant correlation between concentration and day and night time. PSA can be reduced after bed rest. Transurethral resection of the prostate (TURP), radical prostatectomy, radiation therapy or hormone therapy can reduce PSA, limited to the capsule. In patients with prostate cancer after radical prostatectomy, PSA can be reduced to 0, PSA can be used as an indicator of treatment failure or recurrence, it should be noted that serum PSA value can be increased by 1 times after rectal examination, cystoscopy After the increase of 4 times, the biopsy TURP can be increased to 53 to 57 times, PSA value 1 week after the digital rectal examination, at least 4 weeks after the biopsy to the basic value, the PSA value will increase when the acute urinary retention caused by prostate hyperplasia Acute prostatitis with chills and fever can increase serum PSA significantly, and then decrease to the basic value after several months. Non-bacterial prostatitis will not cause PSA increase even if there is purulent prostatic fluid. PSA is in immunohistochemistry. It can also be used as a marker to clearly show latent cancer in the prostate and to determine whether metastatic cancer is derived from the prostate. Its specificity is higher than PAP. Gu Fangliu reports a group of patients with prostate. Monoclonal antibodies against specific antigens were examined by histochemistry, and both prostate cancer and metastatic carcinoma were positive. Other types of prostate malignant tumors were negative. Although PSA levels were closely related to the diagnosis and staging of prostate cancer, PSA was The positive rate of patients with benign prostatic hyperplasia is 32.5%47%, and 20% of acute prostatitis and 3.3% of patients with chronic prostate can increase PSA. Therefore, PSA cannot be used alone for the diagnosis and staging of prostate. It must be combined with digital rectal examination and rectum. Ultrasound should be combined with pathology.
3. Cytology and histology
Since cancer cells can be detected in the prostate fluid of prostate cancer patients, prostate cancer can be diagnosed by urinary sediment smear or prostatic fluid smear microscopy, and pathological diagnosis can be obtained by needle biopsy. 80% to 90%.
Transrectal B-ultrasound
Transrectal B-ultrasound examination is a more accurate examination method. It can be found that the tumor nodules with a volume of more than 4ml are often hypoechoic, single or multiple, and a few echogenic cancers are not detected during B-ultrasound examination. Ultrasound examination can be accurate. Understand the three-dimensional image of the tumor and measure the volume of the tumor.
2. Prostate biopsy
Finger-guided perineal or transrectal biopsy has been used for decades, but due to poor accuracy, the rate of diagnosis of earlier cancer nodules is low. In recent years, transrectal B-guided biopsy has been used. Higher, first to do a digital rectal examination to understand the location of the nodule or abnormal palpation area, and then do a rectal B-ultrasound examination, the accuracy of the biopsy of the hypoechoic nodules is high, due to the hypoechoic zone in the peripheral zone of the prostate and the central zone Not specific, and the prostate extends from the head-to-tail direction to an average length of only 4 cm. Stamay recommends a systemic biopsy for transrectal B-ultrasound, and 3 for each of the two lateral lobes in the sagittal plane. Puncture, take out a total of 6 pieces of 15mm cylindrical tissue, the outer layer of the whole layer of tissue in this plane rarely exceeds 10mm, are included in the tissue taken, because the distal (deepest) needle core tissue is taken from the sample of the moving belt, The distal end of the living tissue was labeled with blue ink prior to placement of the formaldehyde solution to show the transition zone tissue.
System biopsy can understand:
1 range of cancer (volume);
2 Estimate the total Gleason grading of the entire tumor;
3 determine the location of the tumor in the tip of the prostate or bladder neck, can help avoid positive margins;
4 pairs of palpable B1 cancer, when the ultrasound examination is equal echo (21%), system biopsy is the only way to understand whether the tumor invades another leaf, better differentiated cancer (Gleason 3) For mild hypoechoic or equal echoes, such tumors have a great chance of cure. It is often found that such tumors located in the peripheral zone or central zone often need to be diagnosed by system biopsy. Three to four biopsy specimens are required for any hypoechoic zone. If six biopsy specimens from three-dimensional space are obtained, more complete data can be obtained to enable the determination of the exact volume of the tumor.
3. Radioimmunoimaging
Radioimmunoimaging with 131I-human seminal plasma protein (r-sm) antibody can show prostate cancer and metastatic cancer lesions. The best imaging time is 96h, T/NT value is 6.9, and 66 cases of 69 prostate cancers. Positive, the positive rate was 95.7%, the smallest detected tumor diameter was 0.5cm, 13 cases of pelvic lymph nodes and bone metastases were detected at the same time, and the source of the lesion was determined. The detection rate was higher than B-ultrasound and CT, radioimmunoassay Imaging is a non-invasive test that can be used as a screening test, but the cost is high, and false negative results can also occur. It is still necessary to cooperate with the above tests to confirm the diagnosis.
4.CT and MRI
CT and MRI are of no value in the diagnosis of stage A and stage B prostate cancer. These two methods cannot show diagnostic images, nor can they provide biological manifestations of cancer. Patients with stage C and D can show tumors by CT and MRI. Whether it extends to the outside of the capsule and the seminal vesicle, with or without compression of the ureter causes hydronephrosis.
5. X-ray inspection
Intravenous pyelography can be found in advanced prostate cancer, prolonged bladder, compression of the ureter, renal ureteral hydrops, and bilateral renal function. When bone metastasis occurs, osteogenic bone destruction can be seen from the X-ray film. Pathological findings can be found. fracture.
6. Bone scan
Radionuclide whole body bone scan can detect prostate cancer bone metastasis earlier than X-ray film. Patients who have undergone radical prostatectomy, if PSA20ng/ml, bone scan will not be found abnormally.
Diagnosis
Diagnosis and diagnosis of prostate cancer in the elderly
Prostate cancer is differentiated from benign prostatic disease. The most common benign diseases of the prostate are benign prostatic hyperplasia and chronic prostatitis. The determination of PAP and PSA and the determination of plasma zinc all contribute to the identification of benign and malignant.
