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Prostate cancer: the story on HearLore | HearLore
Prostate cancer
In 1817, the English surgeon George Langstaff described a prostate mass during an autopsy of a 68-year-old man who had died with lower-body pain and urinary symptoms, marking the first recorded observation of what would become known as prostate cancer. For decades, the disease remained a medical curiosity, with an 1893 report finding only 50 cases described in the entire medical literature. The true scale of the problem only emerged when prostate surgery to relieve urinary obstruction became common around the turn of the 20th century, allowing surgeons to examine removed tissue and discover cancer in as many as 10% of surgical specimens. Today, prostate cancer is the second-most frequently diagnosed cancer in men globally, with around 1.2 million new cases diagnosed each year and more than 350,000 deaths annually. Despite its prevalence, the disease often remains silent for years, with autopsies showing cancer in the prostates of more than 40% of men over age 50 and nearly 70% of men autopsied between ages 80 and 89. This biological reality means that for many men, the disease is present but never causes symptoms or death, creating a complex landscape where the line between a harmless condition and a lethal threat is often blurred.
The Screening Paradox
The discovery of prostate-specific antigen (PSA) in the 1970s revolutionized detection, yet it introduced a profound medical dilemma regarding the value of early diagnosis. A typical man's blood contains around 1 nanogram of PSA per milliliter, but levels above 4 nanograms per milliliter indicate an increased risk, with more than half of men in that group developing cancer. While screening can reduce the risk of dying from the disease, it also leads to the detection of cancers that would never have impacted a man's health, resulting in anxiety, unneeded biopsies, and treatments that cause unwanted complications. Men with PSA levels over 10 nanograms per milliliter face an even higher risk, yet the test is not perfect; benign prostatic hyperplasia, prostate infection, recent ejaculation, and certain urological procedures can all artificially elevate levels. Consequently, major health organizations offer differing recommendations, with some advising against screening for men over age 70 or those with a life expectancy of less than 10 years, as a newly diagnosed prostate cancer is unlikely to impact their natural lifespan. The uptake of screening varies wildly by geography, with more than 80% of men screened in the US and Western Europe compared to only 20% in Japan and rare screening in regions with a low Human Development Index.
The Gleason Score
When a biopsy is performed, the pathologist assigns a Gleason score, a numerical system that determines the future trajectory of the disease and the urgency of treatment. This score ranges from 3, representing tissue most similar to healthy prostate, to 5, representing the most severely cancerous tissue, with the final score calculated by adding the two numbers that represent the largest areas of the biopsy sample. A Gleason score of 6 is the lowest possible score and represents the best prognosis, while a score of 10 represents the worst. These scores are grouped into five grade groups, where a score of 7 can be either grade group 2 or 3 depending on which Gleason score covers more area, and scores of 9 or 10 are designated as grade group 5. The staging system combines these scores with PSA levels and imaging results to categorize cancer cases into one of four stages, with stage 1 to 4 indicating the extent of growth and spread. This grading system is critical because it dictates whether a man will undergo active surveillance, monitoring the tumor with regular tests to ensure it has not grown, or if he requires immediate intervention such as radiation therapy or radical prostatectomy.
When was prostate cancer first recorded in medical history?
The first recorded observation of prostate cancer occurred in 1817 when English surgeon George Langstaff described a prostate mass during an autopsy of a 68-year-old man. This case marked the initial documentation of what would later become known as prostate cancer.
What percentage of men over age 50 have prostate cancer according to autopsies?
Autopsies show that cancer is present in the prostates of more than 40% of men over age 50. Nearly 70% of men autopsied between ages 80 and 89 also have the disease, indicating it is often present but never causes symptoms or death.
What PSA level indicates an increased risk of prostate cancer?
Levels above 4 nanograms per milliliter indicate an increased risk of prostate cancer. More than half of men in that group develop cancer, while men with levels over 10 nanograms per milliliter face an even higher risk.
What is the highest Gleason score for prostate cancer and what does it mean?
A Gleason score of 10 represents the most severely cancerous tissue and the worst prognosis. Scores range from 3 to 5, with the final score calculated by adding the two numbers that represent the largest areas of the biopsy sample.
When did Charles Huggins publish studies on prostate cancer treatment?
Charles Huggins and Clarence V. Hodges published studies showing that surgical castration or oral estrogen could reduce androgen levels in 1941. This discovery earned Huggins the 1966 Nobel Prize in Physiology or Medicine.
What is the five-year survival rate for men with metastatic prostate cancer?
The five-year survival rate for men with metastases in distant body sites remains relatively poor at 30 to 40 percent. Bone metastases are present in around 85% of those with metastatic prostate cancer and are the primary cause of symptoms and death.
The history of prostate cancer treatment was fundamentally altered in 1941 when Charles Huggins and Clarence V. Hodges published studies showing that surgical castration or oral estrogen could reduce androgen levels and improve symptoms, earning Huggins the 1966 Nobel Prize in Physiology or Medicine. This discovery established that prostate cells require androgens, or masculinizing sex hormones, to survive, and that reducing these levels could halt tumor growth in more than 95% of those treated. However, the disease eventually evolves resistance, leading to a stage called castration-resistant prostate cancer (CRPC) where tumors continue to grow despite reduced testosterone levels. In the 1960s, large studies showed that estrogen therapy was as effective as surgical castration but carried an increased risk of blood clots, leading to the development of GnRH agonists like leuprolide and goserelin by Andrzej W. Schally, who was awarded the 1977 Nobel Prize for his work on GnRH. Despite these advances, CRPC remains incurable and kills a majority of those whose disease reaches this stage, necessitating a sequence of therapies including the chemotherapy drug docetaxel, which was approved in 2004 as the first chemotherapy to increase survival in these patients.
The Bone Metastasis
While early-stage prostate cancer often remains confined to the prostate with a 99% survival rate at 10 years, the disease becomes most dangerous when it metastasizes to other areas of the body, particularly the bones and lymph nodes. Bone metastases are present in around 85% of those with metastatic prostate cancer and are the primary cause of symptoms and death, causing severe bone pain, leg weakness, or paralysis. A quarter of those with metastatic prostate cancer develop a bone fracture, and growing metastases can compress the spinal cord, causing weakness in the legs and feet or limb paralysis in up to 12% of cases. The pain associated with these metastases can be unpredictable, with patients experiencing breakthrough pain that resolves within around 15 minutes before pain medications can take effect. Treatments for bone metastases include external beam radiation therapy to shrink nearby tumors, radioactive compounds like radium-223 that accumulate in bone, and systemic chemotherapeutics that reduce pain by shrinking tumors. Despite these interventions, the five-year survival rate for men with metastases in distant body sites remains relatively poor at 30, 40%, highlighting the lethal nature of the disease once it escapes the prostate.
The Genetic Blueprint
Prostate cancer is caused by the accumulation of genetic mutations to the DNA of cells in the prostate, affecting genes involved in cell growth, replication, and DNA damage repair. Some genomic alterations are particularly common in early prostate cancer, such as gene fusion between TMPRSS2 and the oncogene ERG, which occurs in up to 60% of prostate tumors, and mutations that disable SPOP in up to 15% of tumors. As the disease progresses to metastatic stages, the genetic landscape changes, with mutations in genes like p53 and RB1 becoming more common, and mutations in DNA repair-related genes like BRCA2 and ATM found in at least 7% and 5% of metastatic disease cases respectively. Men with an affected first-degree relative have more than twice the risk of developing prostate cancer, and those with two first-degree relatives have a five-fold greater risk compared with men with no family history. Variations in the BRCA2 gene can increase risk up to eight-fold, while variants in the HOXB13 gene increase risk three-fold, demonstrating that genetics play a significant role in the development and aggressiveness of the disease.
The Modern Surgeon
The surgical treatment of prostate cancer has evolved from the perineal prostatectomy first performed in 1904 by Hugh H. Young at Johns Hopkins Hospital to the robot-assisted surgeries common in wealthier countries today. Young's method became the widespread standard, initially done primarily to relieve symptoms of urinary blockage, but it was later improved upon by Patrick C. Walsh's 1983 description of a retropubic prostatectomy approach that avoided damage to the nerves near the prostate, preserving erectile function. Modern radical prostatectomy aims to surgically remove the cancerous part of the prostate, along with the seminal vesicles and the end of the vas deferens, with robotic tools allowing for small and exact movements that result in shorter hospital stays and less blood loss. However, the skill and experience of the individual surgeon are among the greatest determinants of success, as damage to nearby tissue during surgery can result in erectile dysfunction and urinary incontinence. For those who cannot undergo surgery, radiation therapy offers an alternative, delivered by intensity-modulated radiation therapy or brachytherapy, where a radioactive source is surgically inserted into the prostate to destroy the tumor.
The End of Life
As men with metastatic prostate cancer approach the end of their lives, they often experience confusion, hallucinations, and trouble recognizing loved ones, caused by conditions such as kidney failure, sepsis, dehydration, and the side effects of various drugs, especially opioids. In their last few days, affected men's breathing may become shallow and slow, with long pauses between breaths, accompanied by a rattling noise as fluid lingers in the throat, though this is not uncomfortable for the affected person. Their hands and feet may cool to the touch, and skin become blotchy or blue due to weaker blood circulation, while many stop eating and drinking, resulting in a dry-feeling mouth. The psychological toll is significant, with people with prostate cancer being around twice as likely to experience anxiety or depression compared to those without cancer, and psychological interventions such as cognitive behavioral therapy can help reduce distress. Despite the medical advances in treatment, castration-resistant metastatic prostate cancer remains incurable, and the disease eventually kills a majority of those whose condition reaches this advanced stage, leaving families to navigate the final days of a man who has fought a silent enemy for years.