bubble_chart Overview

Prostate cancer is one of the leading causes of cancer-related deaths among men in Europe and America. The incidence increases with age, with half of men over 80 showing cancerous lesions upon prostate examination. However, the actual clinical incidence is much lower than this figure. There are significant regional and racial differences in prostate cancer incidence, with statistics showing the lowest rates among Chinese, the highest among Europeans, and intermediate rates among Africans and Israelis. Countries like China and Japan are considered low-incidence regions for prostate cancer. However, unselected autopsies of men over 50 reveal that the number of latent cancerous lesions in the prostate is similar to that in Europe and America. This has led some to believe that prostate cancer grows more slowly in Eastern populations, resulting in fewer clinical cases. Additionally, prostate cancer is also associated with environmental factors.

bubble_chart Etiology

The reasons why prostate cells develop into cancer remain unclear to this day. A 1985 U.S. report suggested that oncogenes are the most critical factor. Viruses are also a possible cause of disease. The relationship between sex hormones and prostate cancer is well-known—castration during adolescence prevents prostate cancer, and suppressing androgens can eliminate prostate cancer. Statistics indicate a correlation between sexual activity during adolescence and the incidence of prostate cancer, with excessive sex hormones during adolescence being a contributing factor. Evidence shows that prostate cancer has a familial predisposition. Among environmental factors, cadmium is now considered significant for the lipid metabolism and function of prostate cancer. In Alberta, Canada, there is a village with an extremely high incidence of prostate cancer, where the cadmium content in drinking water is also elevated, warranting attention.

bubble_chart Pathological Changes

Over 95% are adenocarcinomas, with the remainder being transitional cell carcinomas, squamous cell carcinomas, and fleshy tumors. Prostate cancer originates from its acini and ducts, often arising in the peripheral zone (i.e., the area that becomes atrophied in old age due to compression by hyperplastic periurethral glands). Cancer can occur in any part of the prostate, but the vast majority of malignancies are in the peripheral zone. The prostate acini are structures arranged in a linear radial pattern from the urethra, and during carcinogenesis, the histological variations are extreme, disrupting the glandular arrangement. Grading prostate cancer cells is challenging because of the significant cellular differences among tissues. Often, the most poorly differentiated cells are used to represent its biological characteristics, which affect prognosis. Prostate cancer is frequently multifocal, with single nodules accounting for less than 10%.

Within the prostate, nerve bundles are adjacent to the acini, so cancer most commonly invades the perineural space, accounting for over 85%. The spread of prostate cancer can occur through three pathways: local, lymphatic, and hematogenous.

After originating in the acini, prostate cancer often extends toward the urethra. The prostate acinar membrane is an important barrier; if the membrane is breached, the prognosis is poor. Advanced-stage tumors may invade the urethra, bladder neck, and seminal vesicles. Invasion of the bladder trigone leading to ureteral obstruction is also not uncommon, but rectal invasion is generally rare.

The first lymph nodes to be invaded are the obturator-internal iliac chain, though the obturator lymph nodes in the obturator region are usually spared. Bone metastasis is the most common hematogenous spread, with the most frequent sites being the pelvis, lumbar vertebrae, femur, thoracic vertebrae, and ribs. Visceral metastases occur in the lungs, liver, adrenal glands, etc. Among those who die from prostate cancer, 25% have lung metastases, but clinically detected lung metastases account for less than 6%.

Transitional cell carcinomas and squamous cell carcinomas account for less than 3% and often arise from the transitional epithelium covering the ends of the prostatic ducts, sometimes coexisting with adenocarcinoma. The average age of onset is 10 years younger than that of adenocarcinoma, and acid phosphatase levels are often normal. These cancers do not respond to radiation or endocrine therapy and have an extremely poor prognosis.

bubble_chart Diagnosis

Prostate cancer often begins without clinical symptoms and can only be detected as a prostate nodule during a digital rectal examination in a physical check-up. Prostate cancer originates in the peripheral zone of the prostate, making it easily palpable. Urinary retention and hematuria may be related to concurrent benign prostatic hyperplasia, while difficulty in urination and hematuria caused by cancer often indicate an advanced stage. Clinically, a significant number of prostate cancers are discovered through pathological examination of surgical specimens from benign prostatic hyperplasia procedures, and many cases are diagnosed due to symptoms of metastasis.

The diagnosis of prostate cancer focuses on three key points: ① primary tumor; ② lymph node metastasis; ③ distant metastasis.

(1) Primary tumor: A prostate nodule detected by digital rectal examination can be further evaluated through tru-cut biopsy or transrectal Franzen fine-needle aspiration cytology. Transrectal prostate ultrasound can determine the size and extent of the tumor. Normal prostate tissue shows uniform echogenicity, while invasion of the capsule results in unclear boundaries. Changes in echogenicity may also be caused by inflammation or calculi, which should be differentiated. CT and magnetic resonance imaging (MRI) can also assess the extent of the tumor and involvement of the bladder, seminal vesicles, and lymph nodes.

(2) Lymph node metastasis: The first lymph nodes invaded by prostate cancer are the obturator-internal iliac chain, though the lymph nodes in the obturator region are usually unaffected. Clinically, the internal iliac lymph nodes are often referred to as obturator lymph nodes, located medial to the external iliac vein and along the internal iliac vessels. These are the most critical lymph nodes to remove.

In recent years, the diagnosis of lymph node metastasis has relied on CT and MRI, but these methods cannot detect small lesions. Lymphangiography can identify 70–90% of metastases, but its high rates of false negatives and false positives have led to reduced usage. The most valuable diagnostic method is modified lymphadenectomy, which involves removing lymph nodes between the internal and external iliac vessels and the obturator region. This approach provides more accurate staging and avoids complications such as lymph fistula, lymphedema, and lower limb swelling caused by extensive lymph node dissection (e.g., iliac vessels, obturator, pelvic wall, and pre-iliac lymph nodes). Extensive dissection does not prevent existing spread.

(3) Distant metastasis: If intravenous urography reveals ureteral obstruction, it suggests tumor invasion of the seminal vesicles, bladder neck, and lymph nodes, with possible distant metastasis.

Bone metastasis is common, second only to lymph node metastasis. If whole-body isotope scanning shows increased uptake while plain radiographs appear normal, metastasis should be suspected. Chest X-rays can detect lung metastases, which are often due to lymphatic spread, with nodular lesions being rare.

Elevated serum acid phosphatase is associated with prostate cancer metastasis but lacks specificity. Recent advances in radioimmunoassay have improved specificity. Monoclonal antibodies for prostatic acid phosphatase and prostate-specific antigen (PSA) testing are being refined for better specificity. In stage C prostate cancer, 20–70% of cases show elevated acid phosphatase levels, which also rise with lymph node metastasis. Persistent elevation confirms bone metastasis. A postoperative decline in serum acid phosphatase or prostatic acid phosphatase levels is a favorable prognostic sign. In prostate cancer confined within the capsule, acid phosphatase is secreted by prostate cells and excreted through prostatic ducts. In cancer, the ducts may be obstructed by tumor cells, leading to enzyme absorption into the bloodstream and elevated acid phosphatase levels.

Based on these examinations, prostate cancer can be staged. Literature reports indicate stage A accounts for 10–20%, stage B 25%, stage C 25%, and stage D 35%, showing that over half of cases are no longer localized at diagnosis. Clinical staging often underestimates the actual extent of the disease.

bubble_chart Treatment Measures

The treatment of prostate cancer can be divided into radical prostatectomy, radiation therapy, endocrine therapy, and chemotherapy. The choice of method is primarily based on the tumor stage. Stage A1 refers to cancer incidentally discovered during surgery for benign prostatic hyperplasia, with lesions confined to within three high-power fields. Most cases are well-differentiated, and the majority of patients remain stable. Approximately two-thirds of untreated cases progress slowly, with only about 1% potentially dying from the cancer. Due to its favorable prognosis, radical prostatectomy, radiation therapy, or endocrine therapy is generally not recommended. Regular follow-ups, including digital rectal exams and ultrasound, along with serum acid phosphatase measurements, are advised. Stage A2 has a 35% risk of progression without treatment, so radical prostatectomy or radiation therapy should be considered. Stage B prostate cancer should undergo radical prostatectomy. Most B1 cases are well-differentiated, with 5–20% showing lymph node metastasis during surgery. The 15-year cancer-free survival rate post-radical surgery is 50–70%. For B2 cases, radical prostatectomy reveals that 50% have seminal vesicle invasion and 25–35% have lymph node metastasis. If no lymph node metastasis is found during surgery, 86% of cancers remain confined to the prostate. The 15-year cancer-free survival rate for B2 cases post-radical surgery is 25%, prompting some to advocate concurrent radiation therapy. Stage C is more challenging to treat, with half of cases already showing pelvic lymph node metastasis. Radical surgery for Stage C typically requires adjuvant radiation or endocrine therapy, yielding a 5-year survival rate of around 60%, a 10-year survival rate of 30–36%, and a 15-year cancer-free survival rate of 11%. Stage D primarily involves radiation, endocrine, and chemotherapy, with a 5-year survival rate of about 30%. Below, the various treatment methods are discussed separately.

(1) **Radical Prostatectomy** Primarily suitable for prostate cancer confined to the prostate without seminal vesicle or lymph node invasion, radical surgery offers long-term survival. Previously, perineal prostatectomy was common, but retropubic radical prostatectomy is now widely used. Complications include impotence, complete urinary incontinence, stress incontinence, rectal injury, urethrovesical anastomotic stricture, wound infection, thromboembolism, and lymphedema. The surgical mortality rate is 1–5%. Currently, the "nerve-sparing radical prostatectomy" is more commonly performed. (2) **Radiation Therapy** External beam radiation controls 80–90% of Stage A and B prostate cancers. Failure is often due to metastasis (10% from local radiation inefficacy, 25–30% from combined distant metastasis and local inefficacy). About 70% of treated cases occur within 24 months. The 5-year tumor-free survival rate is highest for Stage B (80%) and Stage C (56%). Some reports indicate cancer-free survival exceeding three years even with tumor invasion into the rectum, bladder, pelvic wall, or ureter. Radiation therapy can alleviate metastatic bone pain.

**Complications of Radiation Therapy**: - Acute gastrointestinal reactions (30–40%), often occurring by the fourth week, include diarrhea, rectal discomfort, and tenesmus; about 5% discontinue treatment due to these. - Chronic gastrointestinal complications (12%) include chronic diarrhea, rectal ulcers, strictures, and fistulas. - Urinary complications include frequency, dysuria, hematuria, urethral stricture, and incontinence. - Other reported complications include vulvar and lower limb edema, as well as impotence.

(3) Endocrine Therapy The normal metabolic function of prostate cells depends on androgens, which are converted into dihydrotestosterone (DHT) within the prostate. Testosterone, 90% of which is produced by the testes, circulates in the blood with 57% bound to sex hormone-binding globulin (SHBG), 40% bound to albumin, and only 3% as free, functional testosterone. This free testosterone enters the cytoplasm of prostate cells, where it is converted into DHT. The DHT then binds to receptors, forming a complex that enters the cell nucleus and binds to the DNA of nuclear chromatin. The activated DNA produces mRNA, which encodes proteins essential for prostate cell metabolism. The dependence of prostate cells on androgens varies. Most cancer cells rely on androgens, and endocrine therapy, which directly removes androgens, can inhibit their growth. The more prostate cancer cells resemble normal prostate cells, the more androgen-dependent they are. In contrast, undifferentiated carcinomas and ductal carcinomas often do not rely on androgens, rendering endocrine therapy ineffective. The adrenal glands secrete androstenedione and dehydroepiandrosterone (DHEA), but recent studies suggest these androgens play a minimal role in the initiation and progression of prostate cancer.

(4) Orchiectomy Orchiectomy can reduce serum testosterone from 500ng/dl to 50ng/dl, effectively halting the metabolism of most androgen-dependent prostate cancers and causing tumor regression. Post-orchiectomy symptoms may include paroxysmal fever, sweating, and impotence.

(5) Estrogen Both natural and synthetic hormones can lower testosterone levels via the pituitary-gonadal axis, inhibiting the pituitary release of luteinizing hormone (LH). They also increase sex steroid-binding globulin, reduce intratesticular testosterone synthesis, elevate pituitary prolactin secretion, and decrease DNA synthesis in prostate cells. Commonly used diethylstilbestrol at 1mg–2mg monthly can achieve castrate testosterone levels. However, it may cause cardiovascular complications, and continuous estrogen use for over two years can lead to irreversible castration.

(6) Antiandrogen Drugs Their primary role is to block androgen action on target cells and inhibit DNA synthesis in prostate cell nuclei.

(7) Gonadotropin-Releasing Hormone Analogs (LHRH-A) Prolonged high-dose use of LHRH-A not only initially increases gonadotropin secretion but subsequently suppresses pituitary gonadotropin release. LHRH-A initially raises testosterone production by Leydig cells for about 3–5 months, followed by a decline over 21–28 days to castrate levels. Its advantages include fewer side effects, no cardiovascular complications, and reversible testicular function upon discontinuation. It can also be used to test androgen dependency in prostate cancer; if dependent, treatment can continue or orchiectomy may be performed. The commonly used LHRH-A is Buserelin, achieving chemical castration within a month. Recent long-acting slow-release LHRH-A formulations provide efficacy for up to one month per dose.

(8) Chemotherapy Since 70–80% of prostate cancers are androgen-dependent, endocrine therapy is prioritized. Chemotherapy is typically reserved after failure of endocrine, radiation, and other treatments.

In summary, chemotherapy for prostate cancer is suboptimal, with objective tumor regression rates of 10–15%, a median duration of about 6 months, and survival time around 8 months.

bubble_chart Prognosis

D2 stage: 50% die from prostate cancer within 3 years, 80% within 5 years, and 90% within 10 years.

For any patient who relapses after endocrine therapy, 90% die within 2 years.