Health and Prostate

Due to current recommendations for screening, most patients are asymptomatic at the time of diagnosis. Prostate cancer is often a slowly progressing disease. In fact, many cases are not diagnosed, and death is from causes unrelated to prostate cancer. Patients with locally advanced disease may present with nonspecific symptoms similar to those of benign prostatic hyperplasia (BPH) such as urinary retention, increased urinary frequency, interrupted urine flow, hesitancy, burning or painful urination, dribbling, erectile dysfunction, and painful ejaculation (Table 3). In advanced metastatic disease, patients will often have pain in their lower back and pelvis due to bone metastasis. Prostate cancer can metastasize to the lymph nodes, bone, and visceral organs. The most common site of lymph node involvement is the abdominal and pelvic lymph nodes. Bone metastases are frequently osteoblastic lesions in the lumbar spine. Metastases to the visceral organs include the lung, liver, and adrenal glands. Prostate cancer is graded by how differentiated it is from normal tissue using the Gleason score. The Gleason system is based exclusively on the architectural pattern of the glands of the prostate tumor. It evaluates how effectively the cells of any particular cancer are able to structure themselves into glands resembling those of the normal prostate. The ability of a tumor to mimic normal gland architecture is called its differentiation, and experience has shown that a tumor whose structure is nearly normal (well differentiated) will probably have a biological behavior relatively close to normal – that is, not aggressively malignant.

The principle is fairly simple, and Gleason grading from very well differentiated (grade 1) to very poorly differentiated (grade 5) is usually done for the most part by viewing the low magnification microscopic image of the cancer. There are important additional details that require higher magnification, and an ability to accurately grade any tumor is achieved only through much training and experience in pathology.

Gleason Grades 1 and 2: These two grades closely resemble normal prostate. They are the least important grades because they seldom occur in the general population and because they confer a prognostic benefit which is only slightly better than grade 3. Both of these grades are composed by very pale glands that grow closely together. In grade 1 they form a compact mass; in grade 2 they are more loosely aggregated, and some glands invade into the surrounding muscle of the gland.

Gleason Grade 3: This is the most common grade by far and is considered moderately well differentiated (slightly more differentiated than grades 1 and 2). This is because all three grades have a normal “gland unit” like that of a normal prostate; that is, every cell is part of a circular row, which forms the lining of a central space (the lumen). The lumen contains prostatic secretion like normal prostate, and each gland unit is surrounded by prostate muscle which keeps the gland units apart. In contrast to grade 2, wandering of glands (invading) into the stroma (muscle) is prominent and is the main defining feature.

Gleason Grade 4: This is probably the most important grade because it is fairly common and because if a lot of it is present, patient prognosis is usually (but not always) worsened by a considerable degree. Here also there is a big jump in loss of architecture. There is disruption and loss of the normal gland unit. In fact, grade 4 is identified almost entirely by loss of the ability to form individual, separate gland units, each with its separate lumen (secretory space). This important distinction is simple in concept but complex in practice because there are a variety of differently appearing ways in which the cancer‘s effort to form gland units can be distorted. Each cancer has its own partial set of tools with which it builds part of the normal structure. Grade 4 is like the branches of a large tree, reaching in many directions from the (well-differentiated) trunk of grades 1, 2, and 3. Much experience is required for this diagnosis, and not all patterns are easily distinguished from grade 3. This is the main class of poorly differentiated prostate cancer, and its distinction from grade 3 is the most important grading decision.

Gleason Grade 5: In the process of differentiation this is a significant step towards poor prognosis. Its overall importance for the general population is reduced by the fact that it is less common than grade 4, and it is seldom seen in men whose prostate cancer is diagnosed early in its development. This grade too shows a variety of patterns, all of which demonstrate no evidence of any attempt to form gland units. This grade is often called undifferentiated, because its features are not significantly distinguishing to make it look any different from undifferentiated cancers that occur in other organs.

Gleason score is a grading mechanism based on how the tumor looks at a histologic level and gives information on how aggressive the tumor is. Gleason’s system assigns histologic grade to predominant (primary) and lesser (secondary) pattern of tumor. The grade numbers of the two patterns are added to obtain the Gleason score, which may range from 2 to 10. A Gleason score of 2 to 4 is well differentiated, 5 to 6 is moderately differentiated, and 7 to 10 is poorly differentiated.

The American Urologic System (AUS) is widely used in the United States to stage prostate tumors. The AUS, which includes the Gleason score, gives the overall stage for the patient’s cancer. Gleason score, tumor size, and local extent of the tumor are the prognostic factors for prostate cancer (Table 4). Tumor confined to the prostate is an important aspect to survival. Because differentiation is a factor in determining the stage of prostate cancer, the Gleason score is crucial for an accurate prognosis. Ten-year survival rate is 75% in men with cancer confined to the prostate, while men who have regional extension or metastases have a 55% and 15% 10-year survival rate, respectively.

Controversy surrounds screening for prostate cancer with the main arguments being questionable cost-effectiveness and overdiagnosis when the disease can be indolent and may be at a point where it is medically irrelevant to intervene. Screening for prostate cancer is done by digital rectal exam (DRE) and prostate-specific antigen (PSA). DRE and PSA should be done annually in men starting at age 50, and at age 45 for those who are at high risk (eg, African-American men, and men with a family history of prostate cancer). There are limitations to PSA and DRE. Prostate-specific antigen (PSA) is not specific to men with prostate cancer, as it is also elevated in benign prostatic hyperplasia (BPH). Another disadvantage of PSA is that it cannot predict the stage, aggressiveness, or metastasis of cancer. Although DRE is more specific than PSA for prostate cancer, it is subject to human observation, and the disease is often not localized when diagnosed.

Normal PSA range is based on age and race (Table 2). PSA velocity is a measurement of how much the PSA level is rising over time. When PSA levels increase by more than 0.75 ng/mL per year it may be indicative of prostate cancer. If either PSA or DRE is positive, then further evaluation needs to be done by imaging procedures, such as transrectal ultrasonography (TRUS), and biopsy.

• TRUS uses sound-wave echoes to create an image of the prostate gland to visually inspect for abnormal conditions such as gland enlargement, nodules, penetration of tumor through capsule of the gland, and/or invasion of seminal vesicles; it may also be used for guidance of needle biopsies of the prostate gland and/or guiding the nitrogen probes in cryosurgery.
• Computed tomography scan (also called CT or CAT scan) is a diagnostic imaging procedure that uses a combination of x-rays and computer technology to produce cross-sectional images (often called slices), both horizontally and vertically, of the body. A CT scan shows detailed images of any part of the body, including the bones, muscles, fat, and organs. CT scans are more detailed than x-rays.
• Magnetic resonance imaging (MRI) is a diagnostic procedure that uses a combination of large magnets, radio frequencies, and a computer to produce detailed images of organs and structures within the body.
• Radionuclide bone scan is a nuclear imaging method that helps to show whether the cancer has spread from the prostate gland to the bones. The procedure involves an injection of radioactive material that helps to locate diseased bone cells throughout the entire body, suggesting possible metastatic cancer.
• A (lymph node and/or prostate) biopsy is a procedure in which tissue samples are removed (with a needle or during surgery) from the body for examination under a microscope to determine if cancer or other abnormal cells are present. The diagnosis of cancer is confirmed only by a biopsy.

There are a variety of risk factors associated with prostate cancer (Table 1). Age, race, and genetics are the most likely risk indicators. Although rare before the age of 45, the incidence of prostate cancer escalates rapidly with each subsequent decade. Prostate cancer is more common in African-American men, who tend to have worse prognostic factors at diagnosis. Familial history of prostate cancer greatly increases the likelihood of developing the disease.

Added risk factors that may be associated with prostate cancer include consuming a high-fat/low-vegetable diet, benign prostatic hyperplasia (BPH), occupational exposure to cadmium, and higher testosterone level (eg, African-American men have 15% more testosterone compared to white men).

Prostate cancer is the second most common cancer in men. Pharmacists not only monitor drug side effects, interactions, and adherence but also prevent complications of chemotherapy and guide palliative care.

Pharmacists have an important role in the treatment of patients who have prostate cancer. Monitoring patients for adverse effects of drug therapy, drug/disease interactions, adherence (particularly with hormone therapy), preventing complications from chemotherapy, and guiding palliative care are common areas that pharmacists address in the care of patients with prostate cancer. Prostate cancer patients require special focus on the areas of pain, anti-infective therapy, depression, and anxiety. Through these types of interventions pharmacists can ensure that their patients receive the most effective therapy with the least complications.

Prostate cancer is the second most commonly diagnosed cancer in men in the United States and Canada (after skin cancer) and accounts for 33% of all new cancer cases diagnosed. It is also the second leading cause of cancer death in men and is predicted to result in 10% of all cancer deaths in the year 2003. It is estimated that this year 220,900 new cases of prostate cancer will occur in the US, with 28,900 deaths. Although a significant increase in the incidence of prostate cancer during the late 1980s and early 1990s has been attributed to accessibility of screening tests for prostate specific antigen (PSA), the incidence was rising prior to that time. Currently, the incidence of prostate cancer is on a downward trend. The prevalence of prostate cancer is highest in the United States and Scandinavian countries. Asian countries have the lowest incidence of prostate cancer, while the highest incidence and mortality rates are in African-American men.