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.
| Table 3. Signs and Symptoms of Prostate Cancer |
| • Weak or interrupted urinary stream |
| • Frequent and/or urgent urination, especially at night |
| • Difficulty starting or stopping the urinary stream |
| • Incomplete emptying of the bladder |
| • Painful, burning urination |
| • Blood in the urine or semen |
| • Difficulty in having an erection |
| • Painful ejaculation |
| • Pain or stiffness in the lower back, hips, or upper thighs |
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.
Prostate cancer is shown blocking the urethra, which causes many of the urinary symptoms.
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.
| Table 4. Treatment of Prostate Cancer Based on Prognostic Factors |
| AUS Stage |
Tumor Size and Extent |
Gleason Score |
Current Treatment |
| A |
Nonpalpable, cannot be clinically assessed |
2 – 4 |
Watchful waiting, RP, or RT |
| B |
Tumor may or may not be clinically assessable and is confined to the prostate |
4 – 5 |
Watchful waiting, RP, or RT with or without hormone therapy |
| C |
Tumor localized around the prostate area may or may not extend into adjacent structures |
6 – 7 |
RP or RT, and/or hormone therapy* or chemotherapy |
| D |
Metastasis |
8 – 10 |
Hormone therapy* and/or chemotherapy |
AUS: American Urological System; RP: radical prostatectomy; RT: radiation therapy
*If first-line hormone therapy has failed, secondary hormone therapy can be implemented. |
