Dr. Patrick Walsh's Guide to Surviving Prostate Cancer

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Read This First

There's a "Read This First" in every chapter of this book. This is because prostate cancer—the last thing most men would ever choose to think about—is not just a scary subject to deal with, it's tough to understand. The disease itself is complicated, and the decisions about what to do next can be agonizing. Before you can chart your next course, you've got to sort through, and attempt to make sense of, many things.

If this were a potboiler novel, the kind of page-turner you start on page one and don't put down until you've savored the last word on the last page, you wouldn't need any guidance on how to read it; you'd just get going. If, on the other hand, this were an academic textbook, you might approach it with a highlighter in hand, emphasizing key points and "take-home messages" in bright yellow marker. This book falls somewhere in between, and people read it in different ways. They kick the tires, in effect—flip through the pages; maybe they head directly to a specific section, such as impotence, or biopsy, then backtrack and read about how prostate cancer gets started, or jump ahead to chapters on treatment.

With this in mind, in every chapter we've done our best to give you the highlights—what you really need to know—up front. Consider this your briefing. All of these overviews will familiarize you with the main ideas you'll be covering on the next pages.

That said, this is what you need to know about the anatomy of the prostate:

What is the prostate? The prostate is a small, and probably expendable, organ. Men can live quite comfortably without it. The prostate's biggest job, as far as we know, is to provide part of the fluid that makes up semen. But even this contribution does not appear to be crucial for reproduction—which is why some scientists think the prostate's main role may be to safeguard the reproductive tract from infection in the urinary tract. (In fact, its name in Greek means "protector.") It is not a vital organ. Thus, the major importance of the prostate is not what it does, but what goes wrong with it—the problems it causes to nearly all men who live long enough. These are:

• Cancer of the prostate, the most common cancer in men;

• BPH (benign prostatic hyperplasia, also called "enlargement of the prostate"), one of the most common benign tumors in men and a major source of misery as men get older; and

• Prostatitis, the most common cause of urinary tract infection in men.

If it's not a vital organ, why is it important? Although it's only as big as a walnut, the prostate is a miniature Grand Central Station, a busy hub at the crossroads of a man's urinary and reproductive tracts. It has a highly strategic location, right at the outlet to the bladder. Urine and semen cannot leave the body without passing through the prostate. It is also tucked away, deep within the pelvis, surrounded by vulnerable structures—the bladder, the rectum, the sphincters responsible for urinary control, major arteries and veins, and a host of delicate nerves, some of them so tiny that we've only recently discovered them. This is why any form of treatment for prostate cancer can produce side effects including incontinence, impotence, and rectal bleeding.

What else about prostate anatomy do I need to know? The prostate is like a complicated sponge, with five distinct parts, called "zones." The two most important here are the peripheral zone, which is located next to the rectum, contains most of the glands in the prostate, and is the main site where cancer develops; and the transition zone, which surrounds the urethra, and is the principal site where BPH begins. The prostate's growth and function are stimulated by hormones: Testosterone, produced in the testicles, is converted to another hormone, called dihydrotestosterone (DHT)-the most active male hormone-in the prostate.

The bottom line: In short, the prostate is a gland that does much more harm than good, located in a terrible area that complicates any attempt to treat it. Despite this, as you will learn in this book, there has never been more hope in the treatment of all prostate disorders—especially cancer.

The Prostate's Strategic Location

Welcome to Grand Central Station-the prostate, the bustling, walnut-sized hub at the crossroads of a man's urinary and reproductive tracts. What makes such a small, relatively obscure gland so important to men? The answer is not immediately obvious: The prostate is not, for example, a vital organ like the heart. Its biggest job, as far as we know, is to provide about one third of the fluid that makes up semen. But even this contribution does not appear to be crucial for reproduction—leading some scientists to theorize that the prostate's main purpose actually may be to safeguard the reproductive tract from infection in the urinary tract. (In fact, its name in Greek means "stands before," or "protector.") The prostate has few other redeeming features, isn't necessary for life or even for sexual function, and is known primarily for the clinical problems it causes to nearly all men who live long enough.

What the prostate does have, however, is a highly strategic location, right at the outlet to the bladder. Urine cannot leave the body without passing through the prostate, via a tube called the urethra. (Think of the urethra as an expressway, and the prostate as the Lincoln Tunnel.)

Nothing about the prostate is easy. From a urologist's standpoint, even a routine checkup—to feel for lumps or hardness in a digital rectal examination-is more complicated and takes more skill than many of our patients realize. (For a detailed discussion of diagnosing prostate problems. The prostate is as tucked away—and as surrounded by booby traps—as any of the prizes sought by Indiana Jones in Raiders of the Lost Ark. It lies in the midst of vulnerable structures—the bladder, the rectum, the sphincters responsible for urinary control, major arteries and veins, and a host of delicate nerves, some of them so tiny that we've only recently discovered them—that can foil any physician who ventures into the area without exquisitely precise knowledge of the terrain. This is why any procedure to treat prostate cancer—surgery, external-beam radiation therapy or implantation of radiation "seeds," or attempts to kill cancer cells by cooling or heating the prostate—can produce side effects including incontinence, impotence, and rectal bleeding.

The prostate fits snugly within the pelvis; there isn't much "breathing room" here. Unfortunately, not only is the prostate packed tightly amid other structures, like pieces of a jigsaw puzzle, it is poorly insulated. The flimsy wall of tissue separating the prostate and the seminal vesicles is thinner than a piece of tissue paper—not much of a "buffer zone" for cancer. Consequently, once cancer reaches a critical size, it can easily penetrate the wall (also called the capsule) of the prostate, and escape into this overcrowded region of the body, spreading to the nearby seminal vesicles or lymph nodes, or even further, into the bloodstream.

This is why-even though treatment for prostate cancer is improving dramatically-a man's best protection against this disease is to have it detected as quickly as possible. For the American man at average risk of prostate cancer, this means, after age fifty, a yearly prostate checkup (a physical and digital rectal examination, and a blood test for PSA, prostate-specific antigen. Men at higher risk-African-Americans, and men with a family history of prostate cancer-need to start screening for prostate cancer much sooner, at age forty.

In short, the prostate is a gland that does much more harm than good, located in a terrible area that complicates any attempt to treat it. Despite this, there has never been more hope in our field. At last, we are finding answers to the toughest questions of prostate cancer: Where exactly does it begin, and why? How does it spread? If we can't cure it, can we contain it-can we make advanced prostate cancer a chronic illness, like diabetes, instead of a fatal one? Can we change our thinking, and try drugs that were once considered "last-ditch" measures sooner-can we create adjuvant therapy? Can we actually prevent cancer, or somehow slow its progress with diet? If PSA comes back after surgery or radiation, what does it mean-and how much time do we have to find a more effective treatment? As for radical prostatectomy itself, can we make the operation even better, with fewer side effects and quicker recovery of potency and continence? How can we help men and their families get their lives back? How can we improve quality of life? All of these areas will be covered in detail in later chapters.

A Brief Anatomy Lesson

Although we've tried to keep it brief, this crash course in anatomy may still be more than you ever wanted to know about the prostate and anything even remotely linked to it. But we believe it's essential that you understand where the prostate is and what it does, the two main systems it influences—the reproductive and urinary tracts—and how they can be affected when something goes wrong.

The reproductive tract: For the reproductive organs, the basic act of sexual intercourse is as highly choreographed and synchronized as a NASA shuttle launch. First, the climate must be just right—in this case, the "weather" is a chain of coded chemical messages and hormonal signals. The equipment must be working properly, too. The main vessel, of course, is the penis, a remarkable construction that relies on hydraulic principles for erection, requires a delicate balance between arteries and veins, and is orchestrated by many intricate nerves. Orgasm, the climax of sexual intercourse, involves instantaneous, nearly simultaneous firings of fluid from the prostate, seminal vesicles, and testes (which make sperm). Because the prostate is the focus of this book, we'll begin there, although as you will see, sexual potency and intercourse really begin in the brain.

The prostate: The prostate is a complicated, powerful little factory. Its main products, manufactured in numerous tiny glands and ducts, are secretions-components of semen. During orgasm, muscles in the prostate drive these secretions into the urethra (where it is joined by sperm and fluid from the seminal vesicles), which pumps it out the penis. The prostate's fluid is clear and mildly acidic, and contains many ingredients, most of them designed to sustain sperm outside the body for as long as possible. (These include citric acid, acid phosphatase, spermine, potassium, calcium, and zinc.) Some prostatic secretions also protect the urinary tract and reproductive system from harmful bacteria that may enter the urethra. Here, the prostate truly lives up to its Greek name of "protector": Infections in this area can cause scar tissue to form in the ducts that drain the testicles, leading to infertility. If these infections were common, they would pose a serious threat to procreation—and this may be the major reason why all mammals have a prostate.

After ejaculation, the seminal fluid immediately coagulates-a key part of nature's "safety net" to maximize the odds of reproduction: If semen remained watery, it could not linger in the vagina. (In rats and other rodents, semen actually forms a pelletlike plug, which effectively blocks other rats from depositing their semen in the same female.) The semen is gradually broken down again by an important enzyme made by the prostate-prostate-specific antigen (PSA). PSA's other great value is that it can be detected in a simple blood test. In recent years, this PSA test has become a crucial addition to medicine's arsenal for detecting prostate cancer and monitoring the success of treatment.

Like New York City, the prostate is divided into five zones: Anterior, which takes up one third of the space and consists mainly of smooth muscle; peripheral, the largest segment, which contains three fourths of the glands in the prostate; central, which holds most of the remaining glands; pre-prostatic tissue, which plays a key role during ejaculation-muscles here prevent semen from flowing backward, into the bladder; and transition, which surrounds the urethra and is the epicenter of trouble in benign prostatic hyperplasia (BPH). For reasons not entirely understood, when a man reaches his mid-forties, the prostate tissue in the transition zone tends to enlarge, begins to push nearby tissue for room, and eventually starts to cramp the urethra. With this slow strangulation—think of a man's necktie slowly tightening around his collar-the prostate can make it exceedingly difficult for urine to get from the bladder through the prostate and out of the body. Most prostate cancer occurs in the peripheral zone. Fortunately, this is the region most likely to be felt during a rectal examination and tapped in a needle biopsy of the prostate.

On a microscopic level, prostatic tissue is like a sponge, riddled with tiny glands. These are the micro-factories that produce the secretions, and they're connected by hundreds of ducts, which transport the fluid into the urethra. When these ducts become obstructed-as they do in BPH-PSA levels begin to rise in the bloodstream. Because prostate cancers don't make any ducts, glands in cancerous tissue become isolated. But these ducts still churn out fluid, which has nowhere to go—except into the bloodstream. That's why, gram for gram, prostate cancer contributes ten times more to blood PSA levels than BPH.

Prostate cells come in two basic models—epithelial cells, glandular cells that make the secretions, and stromal cells, muscular cells that hold the epithelial cells in place. The stromal cells aren't just passive scaffolding: They also help the prostate grow. From the stromal cells, in fact, spring many growth factors. And growth factors, we have learned, play a pivotal role in the development and function of the prostate when it is healthy, and when it is cancerous.

How do hormones affect the prostate? The prostate is very sensitive to hormones. In cancer treatment, this is a good thing: Cutting off the supply of these sex hormones, or androgens, can shrink prostate cancer and delay its progression. The hormones that control the prostate begin in the brain: The hypothalamus makes a substance called LHRH (luteinizing hormone-releasing hormone), which it transmits using a "chemical Morse code," or signal pulses, to the nearby pituitary gland. In response, the pituitary makes its own chemical signal, called LH (luteinizing hormone). LH, in turn, controls the testes, which make testosterone. Testosterone is the chief "male" hormone, the cause of-among other things-secondary sex characteristics like body hair and deepening of the voice, and fertility. Testosterone circulates in the bloodstream, and seeps into a prostate cell by diffusion-like water through a coffee filter. To the prostate, testosterone is a raw material: The prostate, using an enzyme called

5-alpha reductase, refines testosterone into another hormone called dihydrotestosterone (DHT). Soon, DHT joins up with a specific protein in the cell's nucleus, and quickly becomes a powerhouse that switches on various genes within the prostate.

The prostate is not required for fertility or potency. Men and animals can remain fertile even if they have had their prostate—or their seminal vesicles, but not both organs-removed. This is surprising, considering that growth of the prostate clearly is linked to a man's sexual development: Starting at puberty, the prostate enlarges five times in size-from a weight of about 4 grams to 20 grams, the size of a walnut-by about age twenty. (For the rest of a man's life, the prostate continues to grow and become heavier, but much more slowly.)

The testes: The testes, or testicles, are a man's reproductive organs: They make the hormone testosterone, as discussed above. They also make sperm, in hundreds of tiny tubes and threadlike, winding tubules. (If these miniature pipes were straightened out, each would stretch to a length of two feet.) There are two testes, each less than two inches long and about an inch wide. The testes, attached to blood-supplying lifelines called spermatic cords, are covered by the scrotum. Have you ever wondered why the scrotum is suspended in such a vulnerable position, below the body? Wouldn't it make more sense-and provide better protection—if the testicles were inside the body? Yes and no. If the testes were tucked away inside the pelvis, they would indeed be better protected-but there wouldn't be much to protect. The testes are located in the scrotum for the simple but expedient reason that it's a more temperate climate down there, by a couple of degrees. Sperm are delicate; they fare poorly when the temperature is too warm. The scrotum, in effect, is nature's cooler. (In fact, men who have undescended testicles-which are located inside the abdomen—cannot develop sperm because the normal body temperature is just too hot.)

The epididymis: The sperm-making tubules in each testis converge to form the epididymis. Compared to the tubules, this is a river, as large and serpentine as the Amazon: Each tubule (one on each side), though only a millimeter wide, could be uncoiled to reach a remarkable length of fifteen to twenty feet. This is one continuous tube—thus, it's easy to see why an infection here could cause scar tissue and blockage that would result in infertility. These tubules are packed side by side, top to bottom, to form the epididymis, an elongated structure about the size of a woman's pinky finger. This is the greenhouse where sperm mature until orgasm, when they shoot from the tail of the epididymis during a series of powerful muscle contractions. The epididymis clings to one side of each testis before turning yet again and heading upward to meet still another tube, called the vas deferens.

The vas deferens: This impressive tube (again, one on each side; together they are called the vasa deferentia), now grown to 3 millimeters in diameter, is a hard, muscular cord, about 18 inches long. Its job is to pump sperm to the part of the urethra that lies within the prostate (the prostatic urethra). Because it is so thick, it can easily be palpated through the scrotum. (It can also be cut easily, in an outpatient procedure—a form of male birth control-called a vasectomy. When the cord is cut, sperm cannot exit the penis through ejaculation, and instead are reabsorbed by the body.) The vas deferens travels to a space between the bladder and rectum, then courses downward to the base of the prostate, where it meets with the duct of the seminal vesicle to form the ejaculatory duct.

The seminal vesicles: The lumpy seminal vesicles, each about 2 inches long, sit behind the bladder, next to the rectum, hanging over the prostate like twin bunches of grapes. Arching still higher over them, on either side, are the vasa deferentia, which meet the seminal vesicles at V-shaped angles; these form the ejaculatory ducts, slitlike openings that feed into the prostatic urethra. The seminal vesicles are made up of caves called alveoli, which make sticky secretions that help maintain semen's consistency. (The vesicles got their name because scientists used to believe they stored sperm; they don't.) Like the prostate, the seminal vesicles depend on hormones for their development and growth, and for the secretions they produce. However: Although the seminal vesicles are strikingly similar to the prostate in many ways, they're almost always free of abnormal growth-benign (as in BPH) as well as malignant.

Lately, scientists at Johns Hopkins have begun exploring the relationship between the prostate and seminal vesicles. What we have learned from their work is that the saga of human evolution is also a story of two male glands-both of which produce fluid that makes up semen. One gland, the prostate, is prone to cancer. The other, the seminal vesicle, is remarkably free of it. In nature, animals that are carnivores-meat-eaters like dogs and lions-don't have seminal vesicles. The only animals that have both prostates and seminal vesicles are herbivores-veggie-eating animals like bulls, apes, and elephants. There is only one exception to this rule: humans. Men have seminal vesicles, too. In other words, man, a meat-lover, has the makeup of an animal that should be a vegetarian.

The penis: The penis-an engineering marvel built of nerves, smooth muscle, and blood vessels—has two main functions—sexual intercourse and urination. (Note: There is no bone in the human penis, although this is not the case in dogs and some other animals.) The penis works like a water balloon. Its basic structure is that of a rounded triangle; all three corners have cylinders of tissue (called the corpora cavernosa and the corpus spongiosum) that fill and become engorged with blood. In erection, as arteries pump a steady supply of blood into the penis, the veins (which normally pump it back out again) clamp down—so the blood can't recirculate, thus keeping the penis "inflated" during sexual activity. All of this is made possible by the delicate nerves that lead to and from the penis. For years, these tiny nerves were poorly understood. The sad result was that removal of the prostate almost always meant impotence. That is no longer the case.

How the Urinary Tract Works

The kidneys are the body's main filters. With each heartbeat, they cleanse the blood of toxic wastes, excess water and salts, and (among many other chores) help maintain the body's balance of fluids and minerals. With more than a million tiny, wadded-up filters called nephrons, the kidneys sift through an incredible volume of fluid—about 45 gallons a day for a 150-pound man. (See Fig. 1.5.) Every sip of water we drink is refined, reabsorbed, and then processed again. (If the water and minerals weren't reabsorbed, our bodies would become seriously dehydrated within hours.) Not all of this material returns to the body, however; much of it passes out as urine. Every day, the average man excretes about two quarts of urine (a concentrated mixture of water, sodium, chloride, bicarbonate, potassium, and urea, the breakdown product of proteins).

Urine exits each kidney through a pipeline called the ureter. The ureters work like toothpaste tubes, squeezing or "milking" urine from the kidneys. Each ureter is about a foot long, and narrow—less than a half-inch wide at its broadest point. Ureters are one-way streets: Urine always flows the same way through them—straight toward the bladder.

The bladder is a big bag. Stretched to its fullest, this muscular tank can hold about a pint of urine. Unlike the kidneys and ureters, the bladder-in normal circumstances-allows us some voluntary control; it generally obeys our decision to eliminate or hold urine. (The inability to control urination is called incontinence.) With intricately woven layers of muscle and connective tissue, the bladder can collapse or expand, depending on the amount of fluid it's asked to hold at a given time. A sophisticated backup system protects the bladder from extreme distention and the risk of rupture: When the bladder is very full, it signals the kidneys to slow down the production of urine. At the neck of the bladder is a gate called the trigone. The purpose of the trigone is to make sure urine flows only one way-downward, away from the ureters and kidneys. The trigone's valve makes a tight seal that prevents urine from backing up into the kidneys, even when the bladder is distended.

The next stop of urine's downward passage is the urethra, another muscular tube, about 8 inches long. This one begins at the neck of the bladder, then tunnels through the prostate at a 35-degree angle and continues into the penis. The urethra is divided into three segments-prostatic (the part that runs through the prostate), membranous (in between the prostate and penis-this is where the external sphincter is located), and penile. Like the prostate, it plays a role in both the urinary and reproductive systems; it serves as a conduit not only for urine, but for sexual fluids. The prostatic urethra has its own gate to prevent fluid backup-a ring of smooth muscle that works with the bladder neck as a clamp during ejaculation. This keeps semen from flowing the wrong way-up into the bladder-and directs its course downward, out the urethra.

That's it for the anatomy crash course. Over the course of this book, as we describe diagnostic procedures, treatments, and complications, you may need to return to this chapter. That's what it's for—to give you a working familiarity with the territory we'll be covering in the next chapters. If it helps, think of these pages as your Michelin Guide to male anatomy. Now that we've discussed the context of the prostate—as a significant gland in both the urinary and reproductive systems—it's time to explain why this tiny gland is so important, and what can go wrong.

Copyright © 2001 by Patrick C. Walsh and Janet Farrar Worthington