Commentary (Crawford): Morbidity of Contemporary Radical Retropubic Prostatectomy for Localized Prostate Cancer

During the past decade, there has been an increase of over 300% in the incidence of prostate cancer and a 150% increase in the death rate from this dreaded cancer. It is estimated that more than 244,000 men will be diagnosed with this neoplasm during 1995, and at least 42,000 will die as a direct result of the disease [1]. Challenged by this dramatically rising incidence and mortality, three strategies can be implemented: (1) attempt to prevent the disease; (2) find the disease early, treat it, and cure it; and (3) discover a cure for the disease once it has escaped the bounds of the prostate.

For the past 50 years, hormonal manipulation has been the mainstay of treatment for advanced disease. More than 80% of patients who have metastatic prostate cancer will respond to hormonal therapy. We recently reported a 25% improvement in overall survival among patients who have metastatic disease when treated with a combination of a luteinizing hormone-releasing hormone (LHRH) agonist and an antiandrogen [2]. Recently, there has been a focus on the potential genetic basis for prostate cancer, with the hope that identifying a specific gene that would lead to new approaches in both prevention and therapy [3].

Advances and discoveries in molecular biology have resulted in significant inroads in our understanding of prostatic carcinogenesis. An exciting new discovery by Pienta et al [4] shows that the oral administration of modified citrus pectin inhibits spontaneous rat prostate cancer metastases. In spite of these advances and promising discoveries, the cure for metastatic prostate cancer remains elusive.

However, advances in the understanding of carcinogenesis have resulted in intense interest in prevention of the disease. The relationship of the male hormone to prostatic development has been known for over a century. Congenital absence of 5-alpha-reductase is a rare syndrome in men that results in the development of a rudimentary or absent prostate [5]. Recognition of this disorder led to the development of the 5-alpha-reductase inhibitor finasteride (Proscar). Since men afflicted with this rare disorder do not develop any disease of the prostate, the logical next step was to initiate a series of studies to determine whether exogenous administration of finasteride could prevent the development of prostate cancer. A large national trial with that goal is currently in progress, with over 18,000 men randomized.

Another important development was the finding that retinoids can alter the development of prostate cancer in the Lobund-Wister rat [6]. Clinical trials are under way to evaluate the salutary effects of retinoids on the prevention of prostate cancer. Even if we learn how to prevent prostate cancer in 1995, however, it will be years before we reap any benefits from such a strategy.

Early Detection Remains Crucial

At present, therefore, early detection and effective treatment would seem to offer the most immediate benefit in reducing the overall mortality of the disease. Prior to 1989, most cases of prostate cancer were either locally advanced or metastatic at diagnosis. In 1995, the exact opposite is true, in that the majority of patients diagnosed have a locally confined lesion [1]. The reason for this change is increased public awareness of the disease, as well as the successful implementation of early detection programs utilizing prostate-specific antigen (PSA) and digital rectal examination.

The whole concept of early diagnosis has remained controversial due to the lack of a large randomized study showing the effectiveness of screening strategies. A National Cancer Institute-sponsored trial assessing the value of early detection of prostate, lung, colorectal, and ovarian cancer is currently underway, and within 15 to 20 years should provide an answer.

There is little question that PSA and digital rectal examination screening are finding cancers earlier. In 1995, men are being diagnosed at a younger age with curable disease, and this, coupled with increased longevity, makes early diagnosis and treatment appealing. In fact, a male who is between the ages of 65 and 70 years at diagnosis has greater than a 50% chance of living another 15 years.

The positive predictive value of an abnormal digital rectal examination and a PSA above 4 ng/mL is 50%. This is almost three times the positive predictive value of an abnormal screening mammogram. Recent refinements in PSA, including age-specific reference ranges and PSA velocity, have increased the positive predictive value of an abnormal PSA, as well as permitted the discovery of earlier stages of the disease [7].

Significance of the Mayo Clinic Data

All of the previous discussion sets the stage for the significance of the article by Lerner et al. The only method that will immediately alter the rising mortality from prostate cancer is early diagnosis and effective treatment. It is important to pursue preventive measures as well as to seek a cure for advanced disease.

A weak link in the former strategy relates to the morbidity and mortality of treatment, as well as the rate of long-term cures. The authors report a very large experience of 1,000 consecutive radical prostatectomies performed at the Mayo Clinic between November 1989 and January 1992. These procedures were done by a number of different surgeons, and the complication rates were compared to rates attained by the same group of surgeons performing the operation prior to 1987.

Recent reviews of the national Medicare experience, as well as patient outcomes research team efforts (Lerner et al's references 17 and 18), would suggest a significant morbidity and mortality from the procedure. The large series from the Mayo Clinic refutes these rather dismal reports, which cite a mortality of 1% and rates of bowel injury of 3%; colostomy, 1.3%; total incontinence, 7%; and urinary stricture requiring long-term treatment, 12%. Lerner and colleagues report rates of 0%, 0.6%, 0%, 0.8%, and 8%, respectively, for the above-mentioned complications. Even the complication rates described in their experience prior to 1987 does not approach those reported in references 17 and 18.

In my own experience of more than 900 radical prostatectomies, complication rates similar to those reported by the authors occur. The only difference is that we have had no cases of rectal injury, but two deaths. These two deaths occurred 7 to 14 days after the surgical procedure, and were the sequelae of a myocardial infarction.

The article does not address the survival rate of patients treated with the procedure. However, other contemporary reports do focus on the principal goal of radical prostatectomy, namely, effecting a cure. The utilization of PSA as a surrogate end point has shown that 85% of men with organ-confined disease will enjoy a 10-year freedom from PSA relapse.

The authors are to be congratulated for their impressive track record with this very difficult operation. Their collective experience, along with the other large series mentioned, appears to support the contention that this surgical procedure should be undertaken only by surgeons who have performed an adequate number of procedures to develop the expertise necessary to achieve the very limited morbidity outlined in this paper.

References:

1. Wingo PA, Tong T, Bolden S: Cancer Statistics 1995. CA Cancer J Clin 45:8-30, 1995.

2. Crawford ED, Eisenberger MA, McLeod DG, et al: A comparison of leuprolide with and without flutamide in previously untreated patients with disseminated prostatic carcinoma-A placebo-controlled randomized trial. N Engl J Med 321:419, 1989.

3. Bova GS, Carter BS, Bussemakers MJ, et al: Homozygous deletion and frequent allelic loss of chromosome 8p22 loci in human prostate cancer. Cancer Res 53:3869-3873, 1993.

4. Pienta KJ, Naik H, Ashtar A, et al: Inhibition of spontaneous metastasis in a rat prostate cancer model by oral administration of modified citrus pectin. J Natl Cancer Inst 87:348-353, 1995.

5. Impearto-McGinley J, Guerrero L, Gautier T, et al: Steroid 5-alpha reductase deficiency in man: An inherited form of male pseudohermaphroditism. Science 186:1213-1215, 1974.

6. Pollard M: The Lobund-Wistar rat model of prostate cancer. J Cell Biochem Suppl 16H:84-88, 1992.

7. Oesterling JE, Martin SK, Bergstralh EJ, et al: The use of prostate specific antigen in staging patients with newly-diagnosed prostate cancer. JAMA 269:57-60, 1993.