Prostate Cancer

Overview

Prostate cancer develops in the prostate gland, a walnut-sized organ located below the bladder and in front of the rectum. The prostate produces seminal fluid that nourishes and transports sperm. Prostate cancer is the most common cancer in men (excluding skin cancers) and the second leading cause of cancer death in men. Approximately one in eight men will be diagnosed during their lifetime, with an average age at diagnosis of 66 years. Most prostate cancers grow slowly and may never cause clinical problems, while others behave aggressively and require prompt treatment. The five-year survival rate exceeds 95% for cancer confined to the prostate.

Unlike benign prostatic hyperplasia, which develops in the central transition zone of the prostate and causes urinary obstruction early, prostate cancer typically arises in the outer peripheral zone. This anatomic difference explains why early prostate cancer rarely produces urinary symptoms and why screening plays such an important role in detection.

Symptoms

Early-stage prostate cancer is often completely asymptomatic. The tumor’s location in the peripheral zone means it does not obstruct the urethra until advanced stages. This silent nature makes screening particularly valuable for men at elevated risk.

When symptoms do occur, they may include difficulty starting urination, a weak or interrupted urinary stream, frequent urination particularly at night, urgency, or blood in the urine. However, these symptoms overlap substantially with benign prostatic hyperplasia and are more commonly caused by that benign condition than by cancer. Blood in the semen, painful ejaculation, or new erectile dysfunction can also occur with locally advanced disease.

Advanced prostate cancer that has spread beyond the prostate causes different symptoms. Bone metastases, which occur in the spine, pelvis, and hips most frequently, produce persistent bone pain, unexplained weight loss, and fatigue. Spinal cord compression from vertebral metastases can cause leg weakness, numbness, or bowel and bladder incontinence, requiring emergency evaluation.

Risk Factors

Age is the strongest risk factor for prostate cancer. The disease is rare before age 40, increases substantially after age 50, and most cases are diagnosed in men over 65. Autopsy studies show that a significant proportion of elderly men harbor microscopic prostate cancer that never caused symptoms during life.

Family history significantly increases risk. Having a first-degree relative with prostate cancer doubles or triples a man’s likelihood of developing the disease. Risk increases further when multiple relatives are affected or when relatives were diagnosed at younger ages. The BRCA1 and BRCA2 gene mutations, known for their association with breast and ovarian cancer, also increase prostate cancer risk, particularly BRCA2.

Ethnicity plays an important role. Men of African ancestry have the highest prostate cancer incidence and are more likely to develop aggressive disease at younger ages. Men of Asian ancestry have lower risk, though this increases with adoption of Western dietary patterns.

Other possible contributing factors include a diet high in red meat and saturated fat, obesity (linked to more aggressive disease at diagnosis), certain chemical exposures, and Agent Orange exposure among veterans.

Diagnosis

PSA (Prostate-Specific Antigen) Testing measures a protein produced by the prostate. Elevated PSA can indicate prostate cancer but also rises with benign prostatic hyperplasia, prostatitis, and recent prostate manipulation. Generally, PSA below 4 ng/mL is considered normal, levels between 4 and 10 ng/mL fall into a gray zone where cancer is found in about 25% of biopsies, and levels above 10 ng/mL carry roughly 50% cancer risk. PSA testing has limitations: it can miss aggressive cancers with deceptively low values and can detect slow-growing cancers that might never cause harm.

Digital Rectal Examination (DRE) allows the physician to feel the prostate through the rectal wall, checking for nodules, asymmetry, or unusual firmness. DRE can detect some cancers missed by PSA testing but has limited sensitivity.

Screening Recommendations emphasize shared decision-making between patient and physician. For average-risk men, the discussion should begin around age 50. For higher-risk men, including those of African ancestry or with a family history, discussion should start at age 45. Men with multiple affected relatives should consider discussion at age 40. Screening is generally not recommended after age 70 or for men with limited life expectancy.

Prostate Biopsy is performed when PSA or DRE findings suggest cancer. Using ultrasound or MRI guidance, the urologist obtains multiple tissue cores (typically 12 or more) for microscopic examination. MRI-fusion biopsy, which targets suspicious areas identified on imaging, improves detection of clinically significant cancers while reducing detection of insignificant tumors.

Staging

The Gleason grading system describes how aggressive prostate cancer appears under the microscope. A pathologist assigns scores from 1 to 5 to the two most prevalent tumor patterns, creating a combined Gleason score from 2 to 10. Gleason 6 cancers are considered low-grade with slow growth potential. Gleason 7 represents intermediate grade, with 3+4 patterns carrying better prognosis than 4+3 patterns. Gleason 8-10 cancers are high-grade with greater potential for aggressive behavior.

The newer Grade Group system simplifies communication: Grade Group 1 (Gleason 6) represents low-risk disease, Grade Groups 2 and 3 (Gleason 7) represent intermediate risk, and Grade Groups 4 and 5 (Gleason 8-10) represent high-risk disease.

The TNM staging system evaluates tumor extent (T), lymph node involvement (N), and distant metastases (M). T1 tumors are not palpable and are found incidentally or on biopsy. T2 tumors are confined to the prostate. T3 tumors extend through the prostate capsule. T4 tumors invade adjacent structures such as the bladder or rectum. N1 indicates regional lymph node metastases. M1 indicates distant metastases, most commonly to bone.

Risk stratification combines PSA, Gleason score, and clinical stage. Low-risk disease (PSA below 10, Gleason 6, T1-T2a) often qualifies for active surveillance. Intermediate-risk disease warrants careful treatment selection. High-risk disease (PSA above 20, Gleason 8-10, or T3-T4) typically requires definitive treatment.

Treatment

Active Surveillance is appropriate for low-risk prostate cancer and involves careful monitoring without immediate treatment. This approach includes regular PSA tests, periodic repeat biopsies (typically every 1-2 years), and MRI monitoring. Treatment is initiated if the cancer shows signs of progression. Active surveillance avoids or delays treatment side effects, and many men on surveillance never require treatment. This approach recognizes that some prostate cancers will never cause harm and that treatment side effects can significantly impact quality of life.

Radical Prostatectomy surgically removes the entire prostate gland and seminal vesicles. Robotic-assisted surgery has become the most common approach, offering precise dissection with smaller incisions. The procedure may also include removal of pelvic lymph nodes for staging. Urinary incontinence typically improves over several months following surgery. Erectile dysfunction is common, though nerve-sparing techniques can preserve function in many men. Infertility is inevitable since semen is no longer produced.

Radiation Therapy provides an alternative to surgery for localized disease with equivalent long-term cancer control. External beam radiation therapy (EBRT) delivers radiation from outside the body over multiple sessions. Modern techniques including IMRT, SBRT, and proton therapy minimize exposure to surrounding tissues. Brachytherapy involves implanting radioactive seeds directly into the prostate, either permanently (low dose rate) or temporarily (high dose rate). Radiation side effects develop gradually and may include urinary symptoms, bowel changes, and erectile dysfunction.

Hormone Therapy (Androgen Deprivation Therapy) exploits prostate cancer’s dependence on testosterone for growth. Treatment options include LHRH agonists or antagonists given as injections, or oral antiandrogen medications. Hormone therapy is used in combination with radiation for intermediate and high-risk localized disease, and as primary treatment for metastatic cancer. Side effects include hot flashes, sexual dysfunction, fatigue, weight gain, bone loss, cardiovascular effects, and cognitive changes.

Focal Therapy treats only the cancer within the prostate while preserving healthy tissue. Options include high-intensity focused ultrasound (HIFU), cryotherapy, and laser ablation. These approaches offer fewer side effects but have less long-term data than traditional treatments and are typically offered to carefully selected patients.

Chemotherapy is reserved for advanced disease that no longer responds to hormone therapy. Docetaxel and cabazitaxel can extend survival in this setting. Newer hormonal agents such as abiraterone and enzalutamide have expanded treatment options for advanced disease. Other treatments for metastatic disease include immunotherapy, PARP inhibitors for men with BRCA mutations, radium-223 for bone metastases, and lutetium-177 PSMA therapy.

When to See a Doctor

Any man experiencing new urinary symptoms should be evaluated, though these symptoms are more commonly caused by benign prostatic hyperplasia than by cancer. Men should discuss prostate cancer screening with their physician based on their age and risk factors.

Seek prompt evaluation for blood in urine or semen, new or worsening bone pain, unexplained weight loss, or any urinary symptoms affecting quality of life. Emergency evaluation is needed for sudden leg weakness or numbness, or for new loss of bladder or bowel control, which could indicate spinal cord compression from metastatic disease.

Men diagnosed with prostate cancer face complex treatment decisions. Understanding your specific cancer characteristics, obtaining second opinions, and consulting with multidisciplinary teams including urologists, radiation oncologists, and medical oncologists helps ensure informed decision-making. Quality of life considerations regarding urinary, sexual, and bowel function should factor prominently into treatment selection alongside cancer control.