Prostate cancer, new options, new hope.

In 1985, 80,000 men were diagnosed with cancer of the prostate in the United States. The American Cancer Society (ACS) reported that 244,000 men were diagnosed with prostate cancer in 1995, and that 40,000 died from the disease. In 1996, the ACS estimates that 317,000 men will be diagnosed with prostate cancer, and that 41,400 will die. The explanation for the increase in diagnosis is the widespread use of PSA (Prostate Specific Antigen) testing, which permits detection of prostate cancer in the earliest stages. PSA is produced only by normal prostate cells, and prostate cancer cells. An increased PSA level ([greater than]4), may lead to a biopsy to establish whether or not cancer is present. PSA can lead to the detection of prostate cancer before the tumor can be felt on a digital rectal examination.

The prostate gland is about the size of a walnut in an adult male. It is located in between the rectum and the bladder. The prostate, along with the seminal vesicles, produces the major volume of semen (ejaculate). The exact function of these secretions is poorly understood, but they may optimize conditions for fertilization. The prostate generally begins to enlarge at age 45-50. Early on, this enlargement is usually benign. However, in later years the incidence of cancer begins to increase.

In autopsy studies of men between the ages of 50-59 years, 29% were found to have prostate cancer. In men over the age of 90 years, 100% were found to have cancer in the prostate. However, most of these cancers did not cause the patients symptoms, and were not life threatening. The lifetime risk of developing a prostate cancer which causes symptoms is estimated to be 9.5%. The lifetime risk of dying from prostate cancer is 3%. The preceding data give a rather curious picture. Prostate cancer is very common. Indeed, if a man lives long enough, the chances are virtually 100% he will get prostate cancer. Yet, in most cases, the disease will not cause symptoms, and in even fewer cases, will the disease be life threatening. Many patients with prostate cancer do not need treatment. Therefore, the key in deciding who needs treatment is to understand who is at risk to develop symptoms and potentially life threatening prostate cancer.

Treatment options for localized prostate cancer include, observation with serial measurement of PSA, hormonal manipulation, radical prostatectomy, cryosurgery, external beam radiation therapy, radiation implants, and proton beam radiation. Only radical prostatectomy and external beam radiation therapy have a long-term proven curative potential. In the 1970s and '80s radical prostatectomy for patients with localized prostate cancer, resulted in 5 and 10 year survival rates of 75-95%, and 52-74%. Results with radiation therapy were similar, with reported 5 and 10 year survivals of 74-96%, and 42-70%. Based on this data, a 1988 National Institute of Health panel of urologists and radiation oncologists. Concluded that overall 10 year survival was comparable with either treatment. However, they noted that disease free survival differences were unknown.

In addition to prognostic factors, the age and general health of the patient should be considered. Patients who have a life expectancy of greater than 10 years should be considered for curative treatment.

In certain patient populations, a physician may advise observation, or "watchful waiting". This policy makes sense in elderly patients with multiple medical problems, where prostate cancer is unlikely to cause mortality. In other groups, where the disease is likely to be life threatening, aggressive local treatment such as radical prostatectomy, should be considered.

Radical prostatectomy is the most frequently performed procedure for localized prostate cancer in the United States. Since all prostate tissue has theoretically been removed, cure is defined as an undetectable PSA level. For patients where the cancer is confined to the prostate, 5 year disease free survival is [approximately] 90%. However, in approximately 50% of patients undergoing radical prostatectomy, cancer has spread outside the prostate. When these patients are included in the survival data, PSA measured 5 year survival drops to [approximately]70%, death due to complications is only 2%. In a recent study of 1716 Medicare patients who had undergone radical prostatectomy, 89% reported impotence, and 31% urinary incontinence. Nerve sparing radical prostatectomy can reduce the risk of impotence to about 50% in healthy patients under 60 years of age. However, little long-term survival data with this technique have been reported.

PSA AFTER RADICAL PROSTATECTOMY CLINICAL STAGE T1-2

INSTITUTION        #PTS      %PS-C      DFS      F/U YEARS

Duke                613       48%       74%           5
Mayo Clinic        3170       53%       52%          10
Wash. Univ.         925       37%       78%           5
UCLA                601       51%       69%           5
Baylor              500       55%       76%           5
Johns Hopkins       955       63%       70%          10
Minnesota            54       50%       67%           2
Stanford            102       53%       85%           1

PS-C Pathologic Stage C; OC - Pathologically Organ confined
patients; ALL - all patients; DFS - Disease Free Survival; F/U -
Follow-up.
PSA AFTER RADIATION THERAPY CLINICAL STAGE T1-4

INSTITUTION         #PTS       CS       DFS      F/U YEARS

Virginia              78      T1-3      76%           7
Univ. Wash.          143      T1-3      77%           2
Basel                 71      T1-4      78%        18 mo.
Wisconsin             63      T1-3      65%           2
Avignon              179      T1-3      75%           4
Stanford(*)          117      T1-3      63%        30 mo.
Mayo Clinic(*)       118      T1-3      92%           3

CS - Clinical Stage; DFS - Disease Free Survival; F/U - Follow-up
* PSA[greater than]1 defined as recurrence.

Another treatment option is Radiation Therapy. For patients in which the disease has not extended beyond the prostate, PSA measured 5 year disease free survival is [approximately] 70%. Temporary radiation side effects can occur during radiation: some chronic effects may also occur. The risk of second malignancy after radiation therapy for prostate cancer has been reported to be the same as in age matched controls who had never received radiation therapy. Of patients who are sexually active before radiation therapy, 72% remain active at 3 years, and 45% at 10 years after radiation. So which therapy is best? To date, no randomized trials comparing radical prostatectomy to radiation therapy have been conducted. Therefore, the best available data comes from comparison of single institution studies. These data indicate that PSA measured 5 year disease free is [approximately] 70% with either radical prostatectomy or radiation therapy. The American Urological Association's Prostate Cancer Clinical Guidelines Panel concluded in 1995 that "the data from the literature do not provide clear-cut evidence for the superiority of any one treatment."

Current experimental treatments include cryosurgery, proton beam radiation therapy, and radiation implants. However, these remain experimental because either no long-term survival results to compare to conventional treatments exist, or to date, no advantage over conventional treatment has been shown, either with respect to long-term survival or complications.

Early detection is important because patients whose prostate cancer has metastasized have a poor prognosis. The two most common sites of metastases are lymph nodes and bone. When the disease has metastasized to lymph nodes, curative potential is extremely small; bone metastases are incurable. Essentially, all other patients with metastatic prostate cancer are also incurable. However, palliative treatments can be given to these patients. Palliative treatments can significantly prolong and improve quality of life in prostate cancer patients. Such treatments include hormonal blockade, chemotherapy, and systemic radioactive isotopes like Strontium-89.

Prostate cancer has become one of the most controversial subjects in oncology in the United States. It is a complex cancer with a broad spectrum of biologic behavior that requires annual checkups for men 40 and over. The ACS has estimated that 41,400 American men will die from the disease this year. Timothy Leary, Bill Bixby, Telly Savalas, Raymond Burr, and Frank Zappa, all died from prostate cancer. One man will die every 13 minutes.

The decision for treatment should be based on the patient's predicted life span in the absence of the disease, together with the prognostic factors which predict the aggressiveness of the cancer. In elderly patients with multiple medical problems, where life expectancy is short, and the mortality risk from causes unrelated to prostate cancer is high, observation is justified. That is also true for elderly patients with early stage prostate cancer, favorable tumor histology, and low PSA, where the natural history of the cancer is likely to be idle. In most other cases, consideration should be given for a curative treatment.

It is important to diagnose the disease in an early, curable stage. During the month of June, the non-profit Cancer Detection Center and the American Cancer Society are sponsoring "Father's Day All Month" for men to obtain a PSA blood test for prostate cancer, plus a urologic exam for $15.00. For more information on the exam and prostate cancer, call the Cancer Detection Center at 213-485-2511, or the American Cancer Society at 213-386-6102.

RELATED ARTICLE: PROSTATE CANCER T-STAGE

T0 No evidence of primary tumor.

T1 Clinically inapparent tumor, not palpable or visible by imaging. These tumors are discovered at the time of TURP (Trans-Urethral Resection of the Prostate) for urinary tract obstructive symptoms, or when a biopsy of the prostate is done because of an elevated PSA.

T2 Tumor confined within the prostate.

T3 Tumor extends through the prostatic capsule.

T4 Tumor is fixed, or invades adjacent structures other than the seminal vesicles.

Rufus J. Mark, M.D. Medical Director, Department of Radiation Oncology Good Samaritan Hospital Assistant Clinical Professor, UCLA Medical Center, Department of Radiation Oncology Chairman, American Cancer Society Prostate Cancer Regional Task Force Robert P. Zimmerman, M.D. UCLA Department of Radiation Oncology American Cancer Society Clinical Oncology Fellow, 1995-96.