Diagnosis and treatment of prostate cancer

Diagnosis and treatment of prostate cancer – includes patient information handout

John Naitoh

Prostate cancer is second only to lung cancer as the leading cause of cancer deaths in American men. In 1997, approximately 209,900 new cases of prostate cancer were diagnosed, and more than 41,800 deaths were attributed to this malignancy.[1] At present, chemotherapy and immunotherapy cannot cure prostate cancer once it has spread beyond the gland. Therefore, curative treatment for localized tumors may be the best hope of lowering the mortality rate for prostate cancer.[1] According to this viewpoint, the primary focus of prostate cancer management should be the detection and aggressive treatment of tumors while they are still confined to the prostate.

The discovery of prostate-specific antigen (PSA) has made it possible to detect tumors before they become palpable on rectal examination. Improvements in radiotherapy and surgical techniques have decreased the complications of treatment and provided acceptable cure rates. However, the enthusiasm for prostate cancer screening must be tempered by the lack of evidence that its routine use can improve the quality and quantity of life for the overall population. Furthermore, a prostate cancer screening program is expensive, and the present treatments for this malignancy can be associated with significant side effects.

The controversial aspects of prostate cancer screening are reviewed in this article. An attempt is also made to identify the patient groups that definitely would benefit from prostate cancer screening. Current treatment approaches for tumors confined to the prostate are also reviewed.

Prostate Cancer Screening Controversy

The effectiveness of a cancer screening program depends on a number of factors. The malignancy must be detectable with minimal harm and cost, and early diagnosis must be able to improve the quantity and quality of the patient’s life. An effective treatment for the cancer must be available, and this treatment should have few side effects. Finally, treatment of the asymptomatic patient must provide a better outcome than treatment after the disease has become clinically evident.

At this time, prostate cancer screening does not fulfill all of the requirements for an effective screening program. Some evidence shows that, compared with screening by rectal examination alone, routine screening of asymptomatic patients with PSA testing and digital rectal examinations detects a higher percentage of cancers that are localized to the prostate.[2] However, both the American Academy of Family Physicians[3] and the U.S. Preventive Services Task Force[4] recently recommended against the use of routine prostate cancer screening for two reasons: (1) early prostate cancer detection has no proven benefit and (2) the potential side effects of treatment may outweigh the benefits. In contrast, the American Cancer Society and the American Urological Association[5] recommend the use of a PSA-based screening program to detect prostate cancer in men 50 years of age and older.

The main problem with prostate cancer screening is that even though this malignancy is extremely common, it is the actual cause of death in only a small proportion of patients who have histologic evidence of prostate cancer. Although data from autopsies indicate that approximately 70 percent of 80-year-old men have prostate cancer,[6] this malignancy is the cause of death in only 3 percent of all men.[7] Prostate cancer is often an incidental finding in elderly patients. The tumor grows so slowly that no symptoms appear; in essence, patients often die of other causes before the cancer causes serious problems. Thus, prostate cancer screening programs may result in the detection and treatment of many asymptomatic cancers that will have no impact on length of life.

In the era of medical cost containment, the expense of a prostate cancer screening program must be considered, especially because other preventive health care measures, including smoking cessation programs, colon cancer screening, vaccination programs and prenatal care programs, may have greater impact on the overall health of the total population. These potentially more useful programs compete for funding with prostate cancer detection programs.

Although an individual PSA test is relatively inexpensive ($20 to $40), expenses multiply when a patient with an abnormal PSA test must be evaluated. Transrectal ultrasound examination costs approximately $100 per patient, and random biopsies cost another $150. Pathologic evaluation of the biopsy specimens costs approximately $300 per patient. When compounded by the fact that three patients without cancer must be evaluated for each cancer that is detected,[8] the estimated overall cost of initiating a nationwide prostate cancer screening and treatment program for all eligible men ranges from $8.5 to $25.7 billion per year.[9]

Prostate cancer screening does have a number of potential benefits. Evidence exists that screening programs based on PSA testing will detect only clinically significant malignancies (i.e., larger and more aggressive tumors that will cause significant symptoms or decrease the patient’s life span if they are left untreated).[10] Furthermore, it is clear that every year more than 40,000 men die from prostate cancer. At present, early detection and treatment are the only effective measures for decreasing the mortality rate for this malignancy. Finally, some evidence shows that the aggressive diagnosis and treatment of prostate cancer is having an effect: 1997 was the first year in which the mortality and incidence rates for prostate cancer were expected to decrease.[11,12] It is too early to attribute these changes to prostate cancer screening programs initiated in the mid-1980s. However, screening programs that use PSA testing have been shown to reduce the number of patients who present with metastatic tumors or markedly elevated PSA levels.[2]

Indications for Prostate Cancer Evaluation

It is reasonable to search for prostate cancer in the male patient who is having difficulty voiding (slow stream, urgency) or hematuria, or who has signs and symptoms of metastatic cancer (bone spread resulting in an elevated alkaline phosphatase level and progressive back pain, sciatica or lower extremity neurologic impairment). Either curative treatments for cancers confined to the prostate (radical prostatectomy or radiotherapy) or palliative treatments for metastatic disease (orchiectomy to eliminate androgen stimulation to the tumor) are likely to decrease symptoms and improve quality of life.

Routine prostate cancer screening in asymptomatic patients is more controversial. The eventual decision to offer prostate cancer screening must be tempered by several factors: (1) prostate cancer has no cure once it has spread beyond the prostate, (2) prostate cancer treatment has potential complications, including impotence and incontinence, and (3) screening may identify a cancer that may never cause symptoms or decrease life expectancy.

The decision to offer prostate cancer screening must be made on an individual basis, depending on the patient’s age, health status, family history, risk of prostate cancer and personal beliefs. The patient must be informed about the risks and potential benefits of screening. The patient also must be helped to realize that while prostate cancer can grow quickly, it generally grows quite slowly. In most men, a high-fat diet, smoking, lack of exercise and excessive alcohol intake can have a greater impact on life span than prostate cancer.

The risk of dying from prostate cancer is higher in certain patients, including all African-American men and men who have a first-degree relative with prostate cancer.[13] Since these men may be genetically predisposed to the development of prostate cancer, the American Urological Associations recommends that they be evaluated with annual PSA testing and rectal examinations, beginning at 40 years of age.

For all other men, prostate cancer screening should be performed at the age of 50 years in those who wish to undergo evaluation. Annual examinations can then be considered. Changes in the rectal examination or a rise in the PSA level of greater than 0.7 ng per mL per year are suggestive of cancer.

Prostate cancer screening probably should not be done once patients are over the age of 70 or if they develop a significant underlying medical illness or other incurable malignancy that will decrease their life expectancy to less than 10 years.

Approach to Prostate Cancer Screening

Patients generally should be evaluated by a urologist if physical examination of the prostate reveals any area of asymmetry, nodularity or induration, because up to 50 percent of these findings will be caused by prostate cancer.[8] The problem with using only the digital rectal examination as a screening tool is that it does not detect cancers before they have spread beyond the prostate. More than 50 percent of prostate cancers diagnosed by digital rectal examination have spread locally or have metastasized to lymph nodes or bone.

The approach to screening has been revolutionized by the discovery of PSA as a serum marker that is 70 to 80 percent sensitive for prostate cancer. This serum marker is a protein made only by prostate cells. Serum PSA levels are proportional to either the total volume of prostate tissue or the amount of irritation in the prostate (such as occurs with carcinoma or inflammation). Either increased volume or irritation causes PSA to spill from the prostate into the bloodstream.

When PSA testing is used alone, it can detect up to 80 percent of prostate cancers. However, the PSA test is not very specific, since only one third of men with an abnormal serum PSA level actually have cancer.[8] Numerous attempts have been made to enhance the ability of PSA to distinguish between benign and malignant disease. The test enhancements that have been tried include the following the free PSA test, which looks at the amount of PSA that is not bound to plasma proteins; the PSA density test, in which PSA levels are adjusted to the size of the prostate; the PSA velocity test, in which PSA changes are observed over time; and PSA age-adjusted ranges, because the PSA level can rise with age. Of all these methods, the use of age-adjusted ranges appears to be the most useful, since this enhances cancer detection in younger patients, who benefit most from early diagnosis and treatment, and decreases the number of biopsies performed in older men, who are at less risk of dying from prostate cancer (Table 1).[14]

TABLE 1

Age-Adjusted Reference Ranges for PSA Levels

Median PSA value Normal PSA range

Patient age (years) (ng per mL) (ng per mL)(*)

40 to 49 0.7 0 to 2.5

50 to 59 1.0 0 to 3.5

60 to 69 1.4 0 to 4.5

70 to 79 2.0 0 to 6.5

Radical Prostatectomy

The prostate is wrapped around the urethra like a doughnut. In radical prostatectomy, the entire prostate is excised from the urethra and bladder, which are then reconnected. Currently, the average hospital stay after radical prostatectomy is two to three days. Most patients are able to eat a regular diet within two days of surgery. Full activity usually can be resumed by one month after radical prostatectomy.

Side Effects

Severe complications from radical prostatectomy are relatively uncommon. However, damage to the urinary sphincter and penile nerves during surgery can result in postoperative urinary incontinence and impotence. According to our review of most current series, only 20 percent of patients who undergo radical prostatectomy have any degree of stress urinary incontinence following surgery, and fewer than 1 percent have severe leakage (Table 3).

TABLE 3

Urinary Incontinence Rates After Radical Prostatectomy

Patients with

Degree of incontinence incontinence (%)

None 81.5

Mild (one pad per day) 14.0

Moderate (multiple pads per day) 3.0

Severe (total incontinence) 1.5

When watchful waiting is being considered, it’s important to be sure patients understand the following: (1) their risk of cancer progression and death from prostate cancer is increased if treatment is deferred; (2) only palliative treatments can be employed if their cancer progresses; and (3) PSA levels must be checked every three to six months to determine if the cancer has progressed. Despite these factors, watchful waiting is definitely a reasonable option in older patients with low-grade prostate cancer and significant co-morbidity. This approach may allow these patients to live a normal life span without the side effects and expense of aggressive treatment programs.[26]

REFERENCES

[1.] Van Eschenbach A, Ho R, Murphy GP, Cunningham M, Lins N. American Cancer Society guideline for the early detection of prostate cancer: update 1997. CA Cancer J Clin 1997;47:261-4.

[2.] DeKernion JB, Belldegrun A, Naitoh J. Surgical treatment of localized prostate cancer: indications, techniques and results. Cancer Surv (In press).

[3.] American Academy of Family Physicians. Summary of policy recommendations for periodic health examination. General population guidelines. AAFP Online, 1997: http://www.aafp.org/family/policy/ camp/app-d.html

[4.] U.S. Preventive Services Task Force. Screening for prostate cancer: commentary on the recommendations of the Canadian Task Force on the Periodic Health Examination. Am J Prev Med 1994;10:187-93.

[5.] Partin AW, Carter HB. The use of prostate-specific antigen and free/total prostate-specific antigen in the diagnosis of localized prostate cancer. Urol Clin North Am 1996;23:531-40.

[6.] Pienta KJ. Epidemiology and etiology of prostate cancer. In: Raghaven D, et al., eds. Principles and practice of genitourinary oncology Philadelphia: Lippincott-Raven, 1997.

[7.] Silverberg E, Lubera JA. A review of the American Cancer Society: estimates of cancer cases and deaths. CA Cancer J Clin 1986;36:9.

[8.] Arcangeli CG, Ornstein DK, Keetch DW, Andriole GL. Prostate-specific antigen as a screening test for prostate cancer. Urol Clin North Am 1997;24:299-314.

[9.] Lubke WL, Optenberg SA, Thompson IM. Analysis of the first-year cost of a prostate cancer screening and treatment program in the United States. J Natl Cancer Inst 1994;86:1790-2.

[10.] Humphrey PA, Keetch DW, Smith DS, Shepherd D, Catalona WJ. Prospective characterization of pathological features of prostatic carcinomas detected via serum prostate specific antigen based screening. J Urol 1996;155:816-20.

[11.] Krongrad A, Lai H, Lamm SH, Lai S. Mortality in prostate cancer. J Urol 1996;156:1084-91.

[12.] Stephenson RA, Smart CR, Mineau GP, James BC, Janerich DT, Dibble RL. The fall in incidence of prostatic carcinoma. On the down side of a prostate specific antigen induced peak in incidence–data from the Utah Cancer Registry. Cancer 1996;77:1342-8.

[13.] Keetch DW, Rice JP, Suarez BK, Catalona WJ. Familial aspects of prostate cancer: a case control study J Urol 1995;154:2100-2.

[14.] Richardson TD, Oesterling JE. Age-specific reference ranges for serum prostate-specific antigen. Urol Clin North Am 1997;24:339-51.

[15.] Smith DS, Catalona WJ, Herschman JD. Longitudinal screening for prostate cancer with prostate-specific antigen. JAMA 1996;276:1309-15.

[16.] Woolf SH. Screening for prostate cancer with prostate-specific antigen. An examination of the evidence. N Engl J Med 1995;333:1401-5.

[17.] Carter HB, Epstein JI, Chan DW, Fozard JL, Pearson JD. Recommended prostate-specific antigen testing intervals for the detection of curable prostate cancer. JAMA 1997;277:1456-60.

[18.] Catalona WJ, Basler JW. Return of erections and urinary continence following nerve sparing radical retropubic prostatectomy. J Urol 1993;150:905-7.

[19.] Catalona WJ, Smith DS. 5-year tumor recurrence rates after anatomical radical retropubic prostatectomy for prostate cancer. J Urol 1994;152:1837-42.

[20.] Patel A, Dorey F, Franklin J, deKernion JB. Recurrence patterns after radical retropubic prostatectomy: clinical usefulness of prostate specific antigen doubling times and log slope prostate specific antigen. J Urol 1997;158:1441-5.

[21.] Consensus conference. The management of clinically localized prostate cancer. JAMA 1987;258:2727-30.

[22.] Shipley WU, Zietman AL, Hanks GE, Coen JJ, Caplan RJ, Won M, et al. Treatment related sequelae following external beam radiation for prostate cancer: a review with an update in patients with stages T1 and T2 tumor. J Urol 1994;152(5 Pt 2):1799-805.

[23.] Goluboff ET, Benson MC. External beam radiation therapy does not offer long-term control of prostate cancer. Urol Clin North Am 1996;23:617-21.

[24.] Albertsen PC, Fryback DG, Storer BE, Kolon TF, Fine J. Long-term survival among men with conservatively treated localized prostate cancer. JAMA 1995;274:626-31.

[25.] Walsh PC, Brooks JD. The Swedish prostate cancer paradox [Editorial]. JAMA 1997;277:497-8.

[26.] Albertsen PC. Early-stage prostate cancer. When is observation appropriate? Hematol Oncol Clin North Am 1996; 10:611-25.

John Naitoh, M.D., is a fellow in urologic oncology at the University of California, Los Angeles, School of Medicine. Dr. Naitoh received his medical degree from the University of California, San Diego, School of Medicine and completed a residency in urology at the University of Connecticut Health Center, Farmington.

Rebecca L. Zeiner, M.D., is an attending physician in family practice with the Southern California Kaiser Permanente Medical Group, West Los Angeles. After receiving her medical degree from the University of California, San Diego, School of Medicine, Dr. Zeiner completed a residency in family practice at Middlesex Hospital, Middletown, Conn.

Jean B. Dekernion, M.D., is the Fran and Ray Stark Professor of Urology and chairman of the Department of Urology at UCLA School of Medicine. Dr. DeKernion earned his medical degree at Louisiana State University School of Medicine, New Orleans, and completed a residency in urology at the University Hospitals of Cleveland.

Address correspondence to Jean B. DeKernion, M.D., Department of Urology UCLA School of Medicine, Box 951738 CHS, 10833 LeConte, Los Angeles, CA 90095-1738. Reprints are not available from the authors.

COPYRIGHT 1998 American Academy of Family Physicians

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