Introduction to prostate cancer

Introduction:

Prostate cancerIt is one of the main causes of cancer death in European and American men. The incidence rate increases with age. Half of the prostates over the age of 80 have cancer lesions, but the actual clinical incidence is far below this number. There are obvious regional and ethnic differences in prostate cancer incidence. According to statistics, the Chinese are the lowest, the Europeans are the highest, and Africa is the highest. In Israel, countries such as China and Japan are low-risk areas for prostate cancer, but there is no choice of males over 50 years old. The number of lesions of the prostate cancer is similar to that of Europe and the United States. Therefore, some people think that the growth of oriental cancer is slower than that of Westerners. There are fewer cases. In addition, prostate cancer is also related to the environment.

Cause:

(1) Causes of the disease

The cause has not been fully identified and may be related to race, genetics, sex hormones, food, and the environment. According to research from countries such as Northern Europe, Sweden, and Finland, a large extent (40%) is due to genetic variation, and recent molecular biology studies have revealed multiple chromosomal aberrations. The complex and interdependent relationship between these factors and environmental carcinogens (60%) is not well understood.

(two) pathogenesis

Several important steps in the cancer-causing mechanism of prostate cancer are now known. About 9% of prostate cancers and 45% of prostate cancers under 55 years of age are due to a hereditary oncogene. It is extremely useful to understand that these genes are undoubtedly understood for the cancer-causing principle of prostate cancer. Recently, Ohio reported that they found that the allelic imbalance in the 23.2 segment of the long arm of chromosome 16 may be a tumor suppressor gene for familial hereditary prostate cancer (Paris et al., 2000). Another idea is that the intensity of the androgen receptor response to androgen in the epithelial cells is inversely proportional to the length of the CAG microsatellite in the 5promotor promoter region of the receptor gene, and the shorter the length, the response of the cells to androgens The stronger, the faster the cells grow. The length of CAG was shorter in blacks and whites with cancer than in the control group. Clearly, the length of the androgen receptor CAG microrepetition region is potentially related to the development of prostate cancer.

DNA methylation changes in the early stages of solid tumor growth, and prostate cancer is no exception. High methylation of DNA can lead to the inactivation of many tumor suppressor genes. For example, the hypermethylation of the short arm of chromosome 17 is inactivated, and tumor suppressor genes in this region may lead to prostate cancer. Prostate cancer growth depends on the balance between cell proliferation and mortality. Normal prostate epithelial hyperplasia and mortality are low and balanced, with no net growth, but when epithelial cells are converted to high grade prostate In high grade prostatic intraepithelial neoplasia (HGPIN), cell proliferation has exceeded cell death. In the early stage of prostate cancer, cell proliferation is due to inhibition of apoptosis (not due to increased cell division, further leading to gene dissimilation). Increased risk. Increased expression of cdc37 gene in precancerous lesions and cancer cells may be an important step in the initiation of canceration.

It has been speculated that the androgen receptor gene is catabolized to allow the androgen receptor to respond to its growth factors, such as insulin-like growth factor I or keratinocyte growth factor. These growth factors are activated by the binding of the growth factor to the androgen receptor after the cancer cells are not sensitive to androgen, resulting in cancer growth. Androgen promotes prostate cancer growth through an androgen receptor-mediated mechanism that enhances the activity of endogenous genetically altered carcinogens, such as estrogen metabolites, estrogen-induced oxides, oxides produced by prostate cancer, and Fat and other substances. In addition, methylation of the androgen receptor is associated with prostate cancer that is not sensitive to hormone therapy in the advanced stage.

The interaction of growth factors with the epidermal matrix is also associated with the development of prostate cancer. Transfoming growth factor-beta, epidermal growth factor, platelet derived growth factor, and neuroendocrine peptides have been shown to be involved in proliferation, differentiation, and invasion of the prostate epithelium. These growth factors produced by the epithelium interact with the tissue matrix to cause stromal cells to produce growth factors, which in turn act on epithelial cells. For example, it has been shown that bone cells secrete growth factors that stimulate prostate epithelial growth, while prostate epithelium is also produced. A growth factor that stimulates bone formation. These explain why prostate cancer can be selectively transferred to the bone.

symptom:

Clinical manifestation

In the early stage of prostate cancer, most patients with prostate cancer have no obvious symptoms, which are often found by chance during physical examination, and can also be found in surgical specimens of benign prostatic hyperplasia.

As the tumor continues to develop, prostate cancer will have a variety of different symptoms, mainly in three aspects:

1. Obstructive symptoms can have dysuria, urinary retention, pain, hematuria or urinary incontinence.

2. Local invasive symptoms The bladder rectal space is often the first to be involved. This gap includes the prostate, seminal vesicle, vas deferens, and the lower end of the ureter. Organs such as tumor invasion and compression of the vas deferens can cause low back pain and side testicular pain. Some patients Also complained that the ejaculation pain.

3. Other metastatic symptoms Prostate cancer is prone to bone metastasis. It can be disease-free at the beginning, and there are also cases of prostate cancer caused by nerve compression or pathological fracture caused by bone metastasis.

98% of prostate cancer is adenocarcinoma, and about 2% is squamous cell carcinoma. 75% originated in the peripheral zone, 20% originated in the transition zone, and 5% originated in the central zone. The staging of prostate cancer is as follows:

T1: T1a is clinically negative, TUR specimen cancer accounts for less than 5% of total volume; T1b is clinically negative, TUR specimen cancer accounts for more than 5% of total volume; T1c is clinically negative, PSA>4μg/L, and biopsy confirms cancer.

T2: T2a is limited to 2 leaves; T2b is limited to 2 leaves.

T3: T3a breaks through the capsule; T3b invades the seminal vesicle.

T4: Violation of surrounding tissues.

N: N0 lymph nodes without metastasis; N1 basin lymph node metastasis; N2 distant lymph node metastasis.

M: M0 has no metastasis in the distance; M1 distant organ metastasis.

Prostate cancer is classified according to gland differentiation, polymorphism, and nuclear abnormality. Gleason classification is used to divide cancer cell differentiation into two major and minor grades, each of which is 1 to 5 points. The scores of the two grades are added together, and the total score is 2 to 4 points, which is a well-differentiated cancer, 5 to 7 points are moderately differentiated cancer, and 8 to 10 are moderately differentiated cancers.

Prostate cancer is mostly androgen-dependent, its occurrence and development are closely related to androgen, and non-hormone-dependent type is only a minority. Prostate cancer can be spread through local, lymphatic and blood lines, and blood is transferred to the spine and pelvis.

diagnosis

1. Early asymptomatic, can be found in the physical examination of the prostate induration, hard as a stone, the surface is not flat.

2. Late symptoms of prostatic hypertrophy, such as frequent urination, dysuria, fine urine flow, difficulty urinating, etc., may be associated with prostatic hypertrophy. However, at this time, rectal examination can be found that the gland is hard and fixed to the surrounding tissue, and the activity is poor, which is very important for clinical diagnosis. Metastatic symptoms such as low back pain, hematuria, weight loss, fatigue, loss of appetite, etc. may also occur.

3. Prostate specific antigen (PSA) serum determination of patients with serum PSA levels can be increased, the ratio of free PSA to total PSA decreased; serum acid phosphatase may increase when there is metastasis. The combined inspection and diagnosis rate of the two is higher.

4. B-ultrasound examination of hypoechoic nodules in the prostate, but must be differentiated from inflammation or stones.

5. Radionuclide bone scans often show metastatic lesions earlier than X-ray films.

6. CT or MRI examination can show prostate morphology changes, tumors and metastasis.

7. Prostate biopsy can be used as a method to diagnose prostate cancer. Failure to puncture and remove the tumor tissue cannot be denied.

diagnosis:

Prostate cancer is a malignant disease that should be detected early and treated early, so it must be differentiated from some diseases to confirm the diagnosis.

(1) should be differentiated from benign prostatic hyperplasia: the two are generally easy to identify. However, in the prostatic glandular gland, some areas of epithelial cells are atypical and can be mistaken for cancer. The main difference is: the acinar in the hypertrophic gland is larger, the surrounding collagen fiber layer is intact, the epithelium is double-layered and high-columnar, the nucleus is smaller than that of the prostate cancer patient, and it is located at the base of the cell, and the gland is arranged regularly to form an obvious knot. Section.

(2) differentiation with prostate atrophy: prostate cancer often begins in the atrophy of the gland, should be noted for identification. The atrophic acinus sometimes gathers tightly, shrinks and becomes smaller, the epithelial cells are cuboid, and the nucleus is large, much like cancer. However, this type of atrophy changes mostly affects the entire leaflet, the collagen connective tissue layer is still intact, the matrix is not invaded, and it itself is sclerotic atrophy.

(3) Differentiation from the squamous epithelium or transitional metaplasia of the prostate: often occurs in the healing part of the infarcted area of the gland, and the squamous epithelium or transitional epithelium differentiate well, without degeneration or division. The most prominent feature of metaplasia is ischemic necrosis or fibrous connective tissue matrix lacking smooth muscle.

(4) Granulomatous prostatitis: the cells are large and can be gathered into a sheet. It has a transparent or reddish stained cytoplasm, a small vesicular nucleus, much like prostate cancer, but it is a macrophage. The other type of cells are pleomorphic, the nucleus is pyknotic, vacuolated, small in size, arranged in rows or clusters, and sometimes some acinus is visible. At the time of identification, attention should be paid to the formation of acinar granulomatous prostatitis, and the relationship between the lesion and the normal glandular duct is unchanged. Degenerative amyloid and multinucleated giant cells are often seen. The cells of prostate cancer are low column or cuboid, with clear cell wall, dense eosinophilic cytoplasm, larger nuclei, staining and morphology, and inactive division. The acinus is small, lacking a curved tube, the normal arrangement is completely lost, irregularly infiltrating into the matrix, and the collagen connective tissue layer is no longer present. The acinus contains a small amount of secretions, but few amyloids. If prostate cancer develops obvious degenerative changes, the tissue structure disappears completely and there is no tendency for acinar formation.

(5) In addition, prostate cancer should be differentiated from prostate tuberculosis and prostatic stones. See the relevant section for details.

diagnosis

1 digital rectal examination: found hard nodules, the correct rate of 80%;

2 more accurate after rectal puncture or perineal incision prostate biopsy;

3 serum acid phosphatase assay: can be significantly elevated.

4B super, isotope scan: the prostate has changed.

5X line: urethral bladder displacement after urethral angiography; spine, pelvis, femur, sternum radiograph, see metastatic bone destruction lesions.

complication:

Lymphatic metastasis The first lymph node invaded by prostate cancer is the obturator-sacral chain. In fact, the lymph nodes in the obturator are generally not invaded. Clinically, the intraorbital lymph node is often called the obturator lymph node. It is located inside the external iliac vein. It is the most important thing to clear the lymph nodes along the iliac vessels.

The diagnosis of lymph node metastasis relies on CT and MR in recent years, but small lesions cannot be found. Lymphatic angiography can detect 70% to 90% of metastases. However, false negatives and false positives are higher, and have been less used in recent years. The most valuable diagnosis of modified lymphadenectomy, that is, the removal of the lymph nodes between the internal and external iliac vessels and the obturator, as a more accurate staging, can avoid the previous removal of the iliac vessels, closed pores, pelvic wall, anterior lymph nodes caused by lymphatic leakage Complications such as lymphadenopathy and lower extremity swelling, because even extensive cleaning does not prevent existing spread.

When distant venous urography reveals ureteral obstruction, it indicates that the tumor has invaded the seminal vesicle, bladder neck and lymph nodes, and there is a possibility of distant metastasis.

Bone metastases are common, second only to lymph nodes. Whole body isotope scan enhancement and normal flat film should be thought of as metastasis. Pulmonary radiography can be found in lung metastases, often in the spread of lymphatic vessels, and nodules are rare.

treatment:

(a) treatment

Treatment of prostate cancer includes follow-up observation, transurethral resection of the prostate (TURP), radical prostatectomy, radiation therapy, cryotherapy, endocrine therapy, and comprehensive therapy. The choice of specific treatment plan should be based on the patient's age, general condition, various examinations, and predicted clinical stage of prostate cancer, tumor histological grade obtained by biopsy specimens, Gleason score, and presence or absence of pelvic lymph node metastases and distant metastases. Other factors determine.

1. Principles of treatment for patients with various stages of prostate cancer

(1) Prostate cancer T1a:

1 observe waiting.

2 radiotherapy.

3 radical surgery: life expectancy > 10 years, Gleason > 7, after Pura > PVA > 4μg / L.

(2) T1b, T1c, T2a, T2b:

1 Life expectancy <10 years, observe waiting or radiotherapy.

2 life expectancy > 10 years, radical surgery or radiotherapy.

(3) T3a:

1 to androgen treatment.

2 radiotherapy.

3 radiotherapy to androgen treatment.

4 can be considered radical prostate surgery (expected life > 10 years, Gleason <7).

(4) T3b, T4, N0:

1 to androgen treatment.

2 radiotherapy.

3 radiotherapy to androgen treatment.

(5) TxN1:

1 observe waiting.

2 radiotherapy to androgen therapy.

3 radiotherapy.

(6) TxN2: androgen treatment.

2. Specific treatment options

(1) The natural course of treatment and treatment of localized prostate cancer: At present, the main treatments for patients with localized prostate cancer (clinical stage T1 and T2) include radical prostatectomy, radiation therapy or clinical follow-up observation. So far, there is no large randomized paired study to directly compare the two methods of surgery and radiotherapy. Some retrospective studies suggest that if the study considers the pathological grade of the tumor and the PSA level, these two The 5-year survival rate of the patients treated by the method was basically the same, and there was no significant difference. Since there is no evidence to suggest which method is better for these two methods, we mainly consider the patient's general condition and health status, the side effects of the treatment, the patient's preferences and wishes, etc. when selecting the appropriate treatment for the patient. . For example, compared with radiation therapy, the risk of urinary incontinence and erectile dysfunction after radical prostatectomy is greater, but has little effect on intestinal function. Therefore, in the treatment of localized prostate cancer, the needs and wishes of patients should be fully considered.

(2) Clinical observation and follow-up: A large proportion of patients with early-stage localized prostate cancer can be followed up for clinical observation without immediate treatment, because the long-term survival rate of these patients during the observation period is the same as that of the same age without prostate cancer. The survival rate is basically the same. Most patients with prostate cancer who were selected for follow-up observation were older patients with short life expectancy, possibly occult tumors, and no obvious clinical manifestations. In addition, due to the small chance of tumor invasion into the rectal bladder space in the transition zone, the possibility of distant metastasis is small, and follow-up observation is also one of the feasible options. Ideal patients for follow-up observation should be patients with serum PSA < 4 ng / ml, short life expectancy, and low tumor pathology. The most appealing aspect of this "therapy" is that it does not have mortality issues associated with various treatments. However, patients often realize that there is untreated cancer in their body, which will cause serious mental burden and psychological burden, which is why people rarely choose to follow up.

(3) Radical prostatectomy: Radical prostatectomy has undergone a century of development. In 1904, Young, a physician at Johns Hopkins University in the United States, completed the first transfemoral radical prostatectomy, which included the entire prostate, seminal vesicle, and Denonvilliers fascia. In 1945, Young reported the results of 184 cases of perineal approach surgery, followed up for 5 to 27 years, the cure rate reached 55%. In 1948, Minin first underwent a radical resection of the prostate after the pubic bone; in 1954, Chute detailed the surgical method of retropubic radical prostatectomy; in 1958, Campbell introduced the transsexual radical prostatectomy. The treatment of surgery. Due to the high incidence of traumatic radical prostatectomy, postoperative urinary incontinence and erectile dysfunction, and high operative mortality, the clinical application of radical prostatectomy is greatly limited. In 1979, Walsh et al. of Johns Hopkins University in the United States proposed a radical prostatectomy technique based on anatomical findings, which greatly reduced the amount of blood loss during surgery and the incidence of postoperative urinary incontinence and impotence. Radical prostatectomy has now been accepted by most urologists as a classic surgical procedure for prostate cancer, especially for localized prostate cancer.

1 radical resection of the posterior pubic prostate: With the emphasis on health screening, more and more prostate cancer is discovered in the early stage. Therefore, prostate cancer patients undergoing radical prostatectomy are also increasing year by year. Compared with the transperineal approach, radical resection of the retropubic prostate can also be performed with pelvic lymphadenectomy, which can accurately assess the involvement of pelvic lymph nodes, and the postoperative pathological staging is more accurate. Therefore, most urologists at home and abroad have used radical retroperitoneal resection of the prostate to treat prostate cancer patients, and the surgical technique is mature. Surgery for patients with prostate cancer who are suitable for surgery can completely remove the tumor in the patient, and the mortality rate of the operation is currently much lower than 1%. However, 2% to 20% of patients will have persistent urinary incontinence after surgery, 70% of patients will have erectile dysfunction, and a considerable number of patients will have anastomotic stenosis after surgery. The causes of postoperative urinary incontinence include injury to the neurovascular bundle during surgery, age of the patient, history of TURP surgery, and urinary control problems before surgery. In order to reduce the incidence of postoperative urinary incontinence, surgery must pay attention to the preservation of the nerves supporting the external urinary sphincter and the ventral plexus. Once attention is paid to the protection of the urinary nerve, the incidence of urinary incontinence after surgery is significantly reduced, and the time to resume control of urination after surgery is also greatly accelerated.

Although the effect of reserving the nerves of the retropubic prostatectomy is controversial, people are very happy to see the advent of CaverMap. This is a device that helps us find and locate neurovascular bundles during surgery, with bright prospects. The use of this device allows us to more accurately detect the nerve vascular bundle during surgery and avoid damage, helping us to determine whether to retain the neurovascular bundle, which can reduce the incidence of post-operative impotence.

Previous studies have also shown that after radical prostatectomy, there may be defects in incomplete tumor resection and low postoperative 10-year disease-free survival. Pound et al reported a 6-year non-PSA recurrence rate of 87% in patients with T1 prostate cancer who underwent radical prostatectomy. Recent improvements in radical prostatectomy techniques will help reduce the positive rate of tumor margins.

Recent studies suggest that preoperative TRUS examination may be helpful in preoperative understanding of the need to adequately remove the tumor at the tip of the prostate and the possible tension during an anastomosis of the bladder and urethra, which may be beneficial in reducing postoperative complications. In addition, it has been suggested that the clinical application of laparoscopic retropubic radical prostatectomy (TLRRP) can also reduce postoperative complications. A recent published study of TLRRP data shows that compared with open surgery. TLRRP has no obvious advantages in the thoroughness of tumor resection, the incidence of urinary incontinence, the incidence of impotence, postoperative hospital stay, length of recovery, and cosmetic effects. The average operation time required for TLRRP is 9.4 hours. In the future, the patient may have a small intestine incision from the puncture site. Therefore, considering these factors, future laparoscopic prostate cancer surgery remains to be further improved and improved.

If the patient's serum PSA drops to undetectable after radical prostatectomy, prostate cancer has been cured. Long-term follow-up of serum PSA after surgery is one of the sensitive indicators to check whether the postoperative cancer persists. The continuous increase of postoperative PSA level often means clinical evidence that the tumor has spread. The most commonly used standard for PSA biochemical recurrence after surgery is a continuous increase in PSA values of more than 0.4 ng/ml in two consecutive serum PSA tests. Recently, it has been suggested that postoperative detection of elevated PSA levels in urine (uPSA) can be used as one of the indicators for local tumor recurrence after surgery. The use of this indicator requires the investigator to massage the bladder urethral anastomosis before taking the specimen to promote the release of uPSA. Because after radical prostatectomy, elevated uPSA can come from the paraurethral gland or from recurrent prostate cancer tissue. Therefore, after artificial stimulation of the bladder and urethral anastomosis, the physician needs to judge whether the elevated uPSA is due to prostate cancer recurrence or other reasons, and further research is needed to understand the value of this index. The sensitivity of pelvic CT to the discovery of tumor recurrence is very low, so it is not recommended to use this test for review.

Although PSA testing has been used as a gold standard for reviewing postoperative recurrence of prostate cancer, many scholars are still working tirelessly to find better biochemical methods for predicting the prognosis of prostate cancer patients and early recurrence of tumors after cure. Bauer et al. used a combination of patient racial, preoperative PSA levels, postoperative Gleason scores, and pathological staging to derive a formula for predicting the likelihood of postoperative recurrence in patients with clinically localized prostate cancer. Postoperative PSNA and PAP levels continue to increase, and patients eventually have tumor biochemical recurrence, suggesting that PAP and PSMA have potential value in predicting the prognosis of patients undergoing radical prostatectomy.

Postoperative pathological staging and vascular involvement are also important in predicting the prognosis of radical prostatectomy. Although PSA can help detect tumor recurrence after radical surgery, postoperative pathological staging is the best indicator for predicting postoperative prognosis. In addition, the content of nuclear matrix protein YL-1 in excised specimens may be promoted in the future, because YL-1 content is one of the potential tumor markers for determining whether prostate cancer patients are advanced prostate cancer and prognosis. Postoperative pathological examination of vascular involvement is also conducive to understanding the prognosis of patients. The study found that postoperative pathological examination found that patients with vascular invasion were 2.5 times more likely to develop locally advanced tumors than patients without vascular invasion. The condition of vascular invasion is also closely related to the invasion of the seminal vesicle, the presence or absence of the capsule, the positive or negative margin of the tumor, the infiltration around the nerve, the high clinical stage, and the high Gleason score, which further emphasizes the blood vessel. Invasion plays an important role in judging the prognosis of patients.

How to treat patients with PSA biochemical recurrence after surgery is still inconclusive. A patient with localized prostate cancer with pathological diagnosis of low pathological grade and low clinical stage tumors, when the PSA once fell to an undetectable level and then re-emerged with PSA biochemical recurrence, it was often local recurrence; Local advanced cancer with a capsule, a positive margin after surgery, and a seminal vesicle are also invaded. This recurrence is mostly distant metastasis. Therefore, different types of relapse require different treatment options. Local recurrence can be given to radiation therapy, and patients with distant metastases should be given systemic endocrine therapy. However, recent literature reports that postoperative pelvic radiotherapy can prevent the development of local tumors in patients with prostate cancer who have developed extracapsular infiltration, normal serum PSA levels, or uninvasive pelvic lymph nodes. Valicenti et al. presented a clinical T3 tumor and postoperatively. Postoperative adjuvant radiotherapy is beneficial in patients with very low PSA levels. In addition, postoperative adjuvant radiotherapy is beneficial for patients with organ-limited tumors after radical surgery, even if there is no PSA recurrence, but it is not appropriate for salvage radiotherapy in patients with extracapsular invasion and biochemical recurrence. Endocrine therapy should be used for this type of patient. The 10-year survival rate for this treatment is reported to be 84%.

2 perineal radical prostatectomy: transesophage radical prostatectomy is the earliest surgical method for the treatment of prostate cancer, because the perineal route surgery can not accurately evaluate the pelvic lymph node metastasis, can not simultaneously pelvic lymphadenectomy, Therefore, the pathological stage of the postoperative patients is still not accurate. This greatly restricts the clinical application of this procedure. In addition, there are certain difficulties in the removal and complete removal of the seminal vesicles after perineal surgery. The high incidence of postoperative impotence also makes most physicians choose the retropubic surgery. However, surgery through the perineal approach also has its advantages, such as the clear urethra of the prostate at the time of surgery, the urethra and bladder are easy to operate, and the intraoperative bleeding is less than the posterior pubic approach. If the anatomical protection of the neurovascular bundle is also noted during surgery, the incidence of postoperative impotence can be reduced.

(4) Radiation therapy and cryotherapy for prostate cancer: Radiation therapy can effectively control prostate cancer, and the local control rate is 65% to 88%. In the past, the main reasons for the failure of radiotherapy for prostate cancer were: insufficient radiotherapy dose, tolerance of tumor cells to radiation, too small calculation of tumor volume, and insufficient effective boundary of irradiation. Nowadays, the development of computer technology has made radiotherapy enter the stage of three-dimensional conformal radiation therapy (3DCRT). The advantage of 3DCRT is that the tumor tissue and the tissue in the surrounding safe area are included in the target area, and the irradiation dose in the target area is increased. The high dose rarely damages the surrounding normal tissue and does not exceed the tolerance of the normal tissue. Factors affecting the efficacy of radiotherapy for prostate cancer include PSA values before and after treatment, and Gleason scores for tumors. The ideal indication for localized prostate cancer to receive radiation therapy should have a longer life expectancy, no significant risk factors for radiotoxicity, and patients are willing to receive radiation therapy. Modern radiation therapy has changed a lot from previous radiotherapy, not only curing the patient's tumor but also being tolerated by most male patients. The side effects of modern radiotherapy are limited, including rectal irritation, diarrhea, frequent urination, and difficulty urinating. The incidence of persistent serious complications is only 1%, including erectile dysfunction, urinary incontinence cystitis, and proctitis. At present, photon beam external beam radiotherapy has become the main choice for patients with prostate cancer receiving radiotherapy. Although it is very difficult to compare the efficacy of surgical therapy with external radiation therapy, it is suggested that the survival rate after treatment is the same as that of biochemical success rate and surgical treatment if the standard radiotherapy dose range is 45-50 Gy. Recently, there is also evidence that patients with a PSA recurrence rate are lower than those of a standard dose when the dose of radiotherapy is >67 Gy, indicating that it is more effective in treating localized prostate cancer.

(5) Treatment of locally advanced cancer and metastatic prostate cancer: Although endocrine therapy has been widely accepted as one of the effective methods for the treatment of advanced prostate cancer, and various antiandrogenic therapies are emerging, how to properly use males Hormone blockade therapy remains controversial. What's more, the subsequent prostate cancer cells from the androgen-dependent to androgen-independent transformation pose a greater challenge to us.

Currently, endocrine treatments for prostate cancer include orchiectomy, estrogens, LHRH analogues, and steroid or non-steroidal antiandrogen drugs. The purpose of these treatments is to reduce the effects of androgens on the prostate, but there are differences in the principles of action, efficacy, and side effects. For a long time, surgical castration or orchiectomy has been considered the gold standard method for endocrine therapy of prostate cancer. Physicians can perform this operation in an outpatient clinic under local anesthesia at a low price. In patients with advanced prostate cancer, 70% to 80% of patients undergoing orchiectomy can achieve different degrees of relief. 80% to 90% of patients with prostate cancer who have undergone bone metastases can disappear after surgery. In addition, the operation has a good effect on patients with prostate cancer with bladder outlet obstruction. The volume of prostate tumors will be significantly reduced 4 to 6 weeks after surgery, and the symptoms of urination will be relieved. Orchiectomy can also be used to rapidly relieve the condition when the bilateral hydronephrosis and the spinal cord are invaded by prostate cancer, and the critical situation such as spinal cord compression and uremia is about to occur.

However, the side effects of surgical castration are also obvious. We cannot ignore the psychological barriers caused by surgery. Rapid decline in testicular androgen levels after surgery can lead to decreased libido and erectile dysfunction. Some patients still have erectile function after surgical castration, and this phenomenon remains to be further studied and explained. 70% of patients will have redness and fever after surgery, such as the simultaneous use of steroid antiandrogen drugsCyclophosphamide(CPA), its progestational effect can alleviate this phenomenon. Other side effects after surgical castration include osteoporosis, weight gain, fatigue, and anemia.

In the process of blocking androgen action, the role of estrogens is to inhibit the secretion of LH from the pituitary secretion and further inhibit the testis.TestosteroneSynthesis and secretion. These drugs can be taken orally, at a low price, and their efficacy is comparable to surgical castration. Therefore, the combination of surgical castration and estrogen drugs has become the first choice for endocrine therapy for prostate cancer. But soon the use of such drugs is limited by its serious cardiovascular system side effects. In addition, estrogen drugs may cause side effects such as thrombosis, heart and brain infarction, water and sodium retention, breast enlargement, and feminization of male breasts.

LHRH analogues such as leuprolide (statin), goserelin (Noride) and other drugs have the same effect of surgical castration plus estrogen drugs. The advent of these drugs makes people go for drugs. The understanding of potential treatment of advanced prostate cancer has undergone great changes and improvements. Although these drugs can also cause the same side effects as surgical castration, the patient's testicles are still present to avoid the patient's psychological problems, while also avoiding cardiovascular disease caused by estrogen application. However, there are still about 5% of patients with facial fever and redness and bone pain, which is caused by the temporary increase of LH and testosterone due to the action of LHRH analogues in the first 2 to 3 weeks of treatment. This side effect can be alleviated if both cyclophosphamide (CPA) is applied.

The previously described surgical castration and drug castration techniques can only reduce the amount of testosterone produced by the testes and do not affect the amount of testosterone produced by the adrenal gland, which may explain why patients cannot be completely removed after undergoing surgical castration or drug castration. Eliminating the effects of DHT, the major androgenic form of the prostate, these patients will develop treatment tolerance after 1-2 years. Thus, the concept of total androgen blockade therapy has been proposed, including both castration and antiandrogen therapy. Antiandrogen preparation can selectively block the action of androgen at the level of prostate. The treatment of androgen blockade can simultaneously block the source of testis and adrenal androgen and promote the apoptosis of prostate cells. Two types of anti-androgen preparations currently used in endocrine therapy for prostate cancer are steroids and non-steroidal drugs. The resistant gland action of both formulations directly acts on the prostate to inhibit the action of androgens by competitively binding to the androgen receptor.

Steroid anti-androgen preparations block androgen action directly at the cell and hypothalamic levels. At the hypothalamic level, its progesterone-like action inhibits the secretion of gonadotropins LH and FSH and inhibits testicular production of androgens. Progesterone side effects include weight gain, hair loss, adrenal insufficiency, changes in carbohydrate metabolism, etc. Progesterone-like effects can also reduce facial flushing. Occasionally, such drugs can cause side effects such as hepatitis, liver tumors, and liver damage. With the blockade of androgen action, libido and erectile dysfunction will inevitably occur. Cyclophosphamide (CPA) is a steroid antiandrogen formulation, and cyclophosphamide (CPA) is still widely used in Europe and other parts of the world, except in the United States. Flutamide, nilu-tamide, bicalutamide and the like are non-steroidal antiandrogen preparations. Unlike steroid antiandrogen preparations, these compounds have no progesterone action and their main advantage is their ability to maintain the patient's libido and erectile capacity.

The purpose of total androgen blockade is to remove tumors from patients, so clinicians should be aware of the development of tumor cells that are not sensitive to androgen. In order to avoid the growth of such tumor cells, we should discontinue the treatment of androgen blockade. In addition, the efficacy of adjuvant therapy with anti-androgen preparations prior to radiotherapy or radical surgery is currently inaccurate and remains to be further studied.

(6) Treatment of prostate cancer that is insensitive to endocrine therapy: Most prostate cancer tumors are composed of different androgen-dependent or androgen-independent tumor cells. The cell types of early prostate cancer are often dominated by androgen-dependent cells. When the patient receives endocrine therapy, the androgen-dependent cells in the tumor rapidly apopulate rapidly, leaving only a small proportion of androgen-independent tumor cells in the tumor, and the latter proliferate. It became the main cell type of the tumor. Although such cells are not sensitive to androgen therapy, such as their rapid proliferation, they will increase sensitivity to currently used chemotherapeutic drugs. However, because prostate cancer cells usually grow very slowly, they are highly resistant to chemotherapy. In view of this, many researchers have long been committed to finding new chemotherapy drugs that can effectively kill cancer cells in non-proliferative phase. The chemotherapeutic drugs found today include Endo-statin, Linomide, tumor angiogenesis inhibitors, and Lapachone (a plant extract). However, their specific efficacy remains to be seen in the future.

Gene Therapy: Because there is still a lack of effective treatments for advanced prostate cancer, scientists have been trying to study prostate cancer cells at the genetic level to find solutions to problems. Although some preliminary studies on gene therapy for prostate cancer have shown that the therapy has a very broad prospect, some therapeutic research is also underway, but gene therapy is truly a common treatment for prostate cancer. There are still many long-term roads to go, and there are many difficulties and obstacles to be overcome. Steiner et al. proposed that the use of transgenic and non-competitive replication of retroviruses can transcribe antisense c-myc fragments into prostate cancer cells, resulting in a reduction in tumor volume implanted in experimental animals. This treatment shows us the prospects of the application. In the future, the main suitable patients for this type of treatment are those with advanced anti-androgen therapy and treatment failure. Prostate cancer gene therapy studies using adenovirus carrying heat-induced suicide genes such as p53, p21 and p16 also yielded satisfactory results in the laboratory. At the same time, scientists applied this method to identify and study the effects of some special proto-oncogenes, such as the androgen-regulated epithelial cell attachment molecule (c-CAM) in prostate cancer cells by both justice and antisense methods. The tumor suppressive effect was studied. Another important part of gene therapy is to activate the tumor cell apoptosis mechanism and promote prostate cancer cells by regulating and modifying a class of genes that induce tumor cell apoptosis, such as protooncogenes and/or tumor suppressor genes such as bcl-2. Apoptosis. Because many gene variants occur during the development of prostate cancer, identifying and using a genetic variant as a potential diagnostic and therapeutic direction for prostate cancer is a very difficult and critical step. Based on this, it is still necessary to conduct in-depth research and evaluation of its efficacy before determining whether gene therapy is a reliable treatment for prostate cancer.

(two) prognosis

Prostate cancer is a common malignant tumor in elderly men. Due to the early symptoms and the older age at diagnosis (mean age is 72 years old), the possibility of advanced or metastasis is increased, such as early diagnosis and treatment. Yes, the prognosis is poor in the late stage.

prevention:

Prostate cancer mainly has the following preventive measures:

1. An effective method currently accepted by the census is to measure the concentration of serum PSA with a digital rectal examination.

Male citizens aged 40 to 45 years were tested with serum PSA levels and were followed up once a year. This census method is cost-effective, such as PSA over 4.0 ng / ml and then a digital rectal examination or ultrasound, if a positive or suspicious then acupuncture biopsy. This method is very effective in detecting early localized prostate cancer. A population-based census in Sweden found that the time span from a serum PSA increase of more than 3 ng/ml to a clinical diagnosis of prostate cancer was 7 years. Therefore, a PSA survey of the population can be used to diagnose prostate cancer early and treat it early. Because PSA blood concentration increases with age, the study of the Gunma University School of Medicine in Japan found that the blood PSA age of men aged 60-64 years, 65-69 years old, 70-74 years old, 75-79 years old and over 80 years old corrected normally. The upper limit of the values should be 3.0, 3.5, 4.0 and 7.0 ng/ml, respectively. The sensitivity, specificity, and efficiency of these normal range were 92.4%, 91.2%, and 84.3%, respectively. The normal upper limit of serum PSA concentration in Austrian men aged 45-49 years and 50-59 years old was 2.5 ng/ml and 3.5 ng/ml, respectively. Many studies have used free PSA percentages to increase the sensitivity of PSA assays for serum PSA 4.0 to 10 ng/ml. In general, the increase in free PSA is seen in benign prostatic hyperplasia, and free PSA is reduced in patients with prostate cancer. Therefore, if the patient with free PSA > 25% is likely (less than 10% probability) without prostate cancer, if <10%, the patient is very likely (60% to 80% probability) with prostate cancer, this time to do prostate A biopsy makes sense.

2. Avoiding risk factors is difficult to achieve in this regard. Because there are many clear risk factors, heredity, age, etc. are unavoidable, but potential environmental risk factors such as high-fat diets, cadmium, herbicides, and other undetermined factors may be avoided. It is now known that approximately 60% of the factors leading to prostate cancer come from the living environment. Studies from Sweden have shown that occupational factors are associated with prostate cancer. The statistically significant occupations are agriculture, related industrial soaps and perfumes and the leather industry, so farmers, tanners and management staff in these industries are There is a significant increase in morbidity. In addition, people exposed to chemicals, herbicides, and fertilizers increase the risk of prostate cancer. According to New Zealand, fish oils containing antioxidants in food can protect and reduce the risk of prostate cancer. Taiwan reported that magnesium in drinking water can prevent prostate cancer. In addition, adhering to a low-fat diet, eating soy-based foods rich in vegetable protein, drinking Chinese green tea for a long time, and appropriately increasing the levels of trace elements such as selenium and vitamin E in the diet can also prevent prostate cancer.

3. Chemoprevention According to the intervention of drugs, chemoprevention can be divided into the following main categories, such as tumor suppressor, anti-tumor growth drugs and tumor progression inhibitors. Because the occurrence and development of prostate cancer is a long-term process, we can use drugs to prevent or inhibit the occurrence and development of prostate cancer. For example, finasteride can inhibit the conversion of testosterone into an active substance that acts on the prostate, dihydrotestosterone, so it may inhibit the growth-promoting effect of testosterone on prostate cancer cells. This effect is still in clinical research observation. Confirmed. Other drugs, such as retinal, have the effect of promoting cell differentiation and anti-tumor progression, and are also in clinical research, and may become potential chemopreventive drugs.