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Changing Trends in the Management of Prostatic Disease in a Single Private Practice: A 5-Year Followup
0022-534 7i93/1502 -034 7$03.00/0 THE JOURNAL OF GRDLDGY Copyright © 1993 by AMERICAN U R O L O GICAL ASSOClATl O N ,
Vol. 150, 347-350,
INC
Printed
1993
[l. S. A.
CHANGING TRENDS IN THE MANAGEMENT OF PHOSTATIC DISEASE IN A SINGLE PRIVATE PRACTICE: A 5-YEAR FOLLOWUP DAVID S. BRESLIN, EDWARD C . MUECKE, JON M. RECKLER AND JOHN A. FRACCHIA From the Section of Urology, Lenox Hill Hospital, New York, New York
ABSTRACT
Evaluation and management services provided by the practicing urologist have changed dramat ically during the last few years. This is particularly evident in the approach to men with bladder outlet symptoms and in those in whom the diagnosis of prostate cancer is a distinct possibility. The impact of medical management/observation of symptomatic benign prostatic hypertrophy, as well as the influence of prostate specific antigen, transrectal ultrasound and biopsy, radical prostatectomy and hormonal agents in a 3-man private clinical practice is analyzed. The records of 2,206 patients new to the practice who presented with a variety of prostate-related complaints from July 1, 1986 to June 30, 1991 were reviewed. Of these patients 1 ,822 (82 % ) were evaluated for presumed benign bladder outlet symptoms. During year 1 of the study, ending on June 30, 1987, 28% of the presumed benign prostatic hypertrophy patients were treated with transurethral prostatectomy, compared to only 8% of such p atients in 199 1 . In contrast, ()'-blocking agents were used to treat 21 % of these patients in 1 99 1 . Transrectal ultrasound biopsy currently accounts for 87% of all prostatic biopsies, increasing 4-fold during 5 years. Radical prostatectomy has increased 6-fold during the course of the study. Administration of a luteinizing hormone-releasing hormone analogue has supplanted orchiectomy and estrogen therapy for the treatment of disseminated disease, as witnessed by a 4fold increase in its use. While it is recognized that these trends are presently applicable to our local metropolitan region, they may reflect practice patterns in similar demographic groups, as well as predict future tendencies nationwide. KEY WORDS: benign prostatic hypertrophy, prostatic neoplasms
From 1980 to 1990 the percentage of men in the United States who were older than 65 years increased approximately 25% over a similar cohort during the previous decade. 1 Cur rently, there are 25 million men in this country older than 50 years and this number is projected to double by the year 2010. 2 Diseases of the prostate, benign and malignant, account for significant health care expenditures in this expanding elderly male population. Because of its relative importance to the practice of urology, various studies have examined practice trends for the management of prostatic disease, particularly benign prostatic hypertrophy (BPH) and cancer. 3 • Transurethral resection of the prostate for BPH is one of the most commonly performed operations in the United States. 5 · For the last several decades this operation has been the most frequent modality for definitive alleviation of bladder outlet obstruction secondary to benign and malignant processes, 7• and it remains the dominant operation in American urological practice. 5 However, alternative options, including watchful waiting as well as the use of specific al-adrenergic blockers, the impending use of hormonal blockade and less invasive procedures, such as transurethral incision, balloon dilation, prostate hyperthermia, intraprostatic coils, laser ablation and so forth, have challenged the role of prostatectomy in the management of benign bladder outlet obstruction. Carcinoma of the prostate remains the most commonly di agnosed male malignancy and accounts for the second highest male cancer death rate. 9 Earlier diagnosis and an aging popu lation are factors increasing the incidence and mortality rates: in the United States approximately 122,000 men will be diag nosed this year 10 and approximately 32,000 will die. 11 Prostate specific antigen (PSA) has become the most useful tumor marker in clinical oncology and may help to identify many patients with subclinical disease. Discovery of elevated serum PSA levels coupled with transrectal ultrasound and 4
biopsy have facilitated earlier diagnosis of prostate cancer. The technique of radical prostatectomy has been refined, and has become an effective, safe method to treat localized carcinoma in selected patients. The use of depot injections of a luteinizing hormone-releasing hormone analogue for patients with met astatic and high risk disease is currently an established treat ment modality. In an effort to assess some of the impact of the aforementioned advances and in an attempt to document future trends in urological practice, we have examined the records of all new patients older than 50 years with prostate-related complaints seen by a 3-man urban private practice during a recent 5 year period ending June 30, 1991.
6
8
Accepted for publication January 22, 1993. Supported in part by a grant from Abbott Laboratories.
347
MATERIALS AND METHODS
The records of all 2,206 new patients older than 50 years old with prostate-related complaints entering a 3-man urology practice between July 1, 1986 and June 30, 1991 were reviewed. Patients were physician-referred or self-referred for a variety of complaints, such as prostatism, prostate nodule assessed by digital rectal examination, elevated serum PSA level or pros tatitis. A number of patients were seen for additional opinions of carcinoma previously diagnosed elsewhere. Routine demographic data were recorded as well as clinical information pertinent to that evaluation, treatment and fol lowup. Initial and subsequent PSA and acid phosphatase levels, when applicable, were documented. The results of digital rectal examination offered an estimation of prostate size and the presence or absence of suspicious features. Patients with presumed benign bladder outlet obstruction and prostatism were managed expectantly, medically or sur gically. Medical management included administration of al adrenergic blockers (dibenzyline , prazosin or terazosin) and/or compounds administered to relieve irritative symptoms, such as oxybutynin, flavoxalate, phenazopyridine and so forth. Pa tients with presumed infectious complaints were treated with
348
CHANGING TRENDS IN MANAGEMENT O F PROSTATIC DISEASE
antimicrobial agents. Surgical therapy included transurethral prostatectomy or open prostatectomy. PSA was assayed with the Hybritech monoclonal method. Transrectal ultrasound of the prostate was performed with a Bruel & Kjaer No. 1846 scanner and a Type 8851 7.0 MHz. probe. Biopsies were performed by digitally directed fine-needle aspiration and histological core sampling or transrectal ultra sound-guided biopsy. The treatment offered to each patient with malignant disease was registered. Options included transurethral resection, radi cal prostatectomy, radiation therapy, hormonal manipulation and observation. Pathological stage was applied to patients undergoing radical prostatectomy. Data were analyzed for significance with the chi-square sta tistic. P values �0.05 infer statistically significant trends in our comparison of the information on a year to year basis. The data are analyzed and reported as percentage of patients per group per year, rather than in absolute numbers, because the number of patients in the individual groups, as well as the total for each year, was not identical. We compared the various changes and trends in our methods of diagnosis and manage ment for each year ending June 30, as described previously. RESULTS
The charts of 2,206 men older than 50 years who were new to the practice with prostate-related complaints were studied (mean 441 per year, range 375 to 477 per year). This group comprised 59% of all new patients who were evaluated by the practice during the 5-year period. Average patient age was 68 years, which showed no significant change during the course of the study (p >0.05) . Patients presented with 1 of 6 different complaints (fig. 1 ) . Prostatism decreased from a high of 389 patients (82 % ) in 1989 to 271 (72 % ) and 296 (67 % ) patients in 1990 and 1991, respectively (p <0.05). Elevated PSA level as a
P R O S TAT E CH ECK 3 % P ROSTAT I T I S 5 %
E L E V P S A 5% N O D U L E 6%
FIG. 1 . Breakdown o f presenting complaint fo r 2,206 patients be tween 1987 and 1991. ELEV, elevated levels. of P ts / y r ---------- - - - ------40 %
--�
30 20 10 0
1987
1988
1989
YEAR
1990
1991
Complaint
1111 N o d u le
� Prostat ism
D E lev PSA
FIG. 2. Comparison of presenting complaint in cancer patients
(Pts. ) . Elev, elevated levels.
35
% of B P H pts/yr
30 25 20 15 10 5 0
1987
1988
- TURP
1989
1990
1991
YEAR � A l p h a b lockade
FIG. 3. Annual comparison of patients treated with transurethral prostatectomy ( TURP) versus a-blockade.
referring complaint increased 300% (60 patients in 1991) during the course of the study (p <0.005) and is currently the leading presenting complaint for patients who are ultimately diagnosed with cancer (fig. 2). Presentation with the complaint of a palpable nodule decreased 67% during 5 years, from 9 % of all patients in 1987 to 3% of all patients in 1991 (p <0.005) . A total o f 1 ,822 patients was evaluated for benign bladder outlet symptoms during the 5 years of the study. In the initial study year (ending June 30, 1987) 28% of 348 patients with BPH were treated with transurethral resection of the prostate, compared to only 8% (29 patients) during the last year (ending June 1991, fig. 3 ) . This 73% decrease in the yearly number of transurethral resections was significant at the p <0.005 level. In fact, all 3 partners in this group performed fewer transure thral resections without significant difference among them (p >0.05). In contrast, 76 BPH patients ( 2 1 %) were managed in 1991 with 1 of the various a-blocking agents (p <0.005, fig. 3). (Such agents were not used routinely during the earlier years of this study.) A total of 384 new patients was evaluated for various stages of prostate cancer throughout the 5 years of the study. At a statistically meaningful level (p <0.0 1 ) , the percentage of pa tients with cancer is increasing, ranging from 14% of all pa tients in 1988 to 21 % in 1990. In 1991 transrectal ultrasound-guided biopsy accounted for 87% of all prostate biopsies (56 patients) in this practice, increasing by greater than 400% during 5 years (p <0.005 ) . In 1987 digitally directed aspiration cytology and/or transperineal core histological biopsies accounted for 90% of all tissue sam pling, while in 1991 only 13% of all patients were so biopsied. Transurethral resection diagnosed 24 cancers (38% ) in 1 987 and only 2 (3%) in 1991. Illustrating the recent influence of PSA, only 2% of the patients who underwent biopsy in 1987 did so solely for an elevation of PSA (with a normal digital rectal examination), while 28% of 1 1 1 biopsies in 1991 were performed for this a reason (p <0.005) . Use o f external radiation therapy as primary treatment has increased by more than 100% during the 5 years (p <0.005) . The use o f brachytherapy has remained constant and low in our practice. Administration of luteinizing hormone-releasing hormone analogues has grown by a multiple of 4 from 1987 to 1991 (14 patients in 1991, p <0.005) , while orchiectomy for androgen ablation has become much less popular (2 patients in 1991, fig. 4). Estrogen administration has diminished by 600% between 1987 and 1991 but, due to overall small numbers, this decreasing tendency is not yet significant at the p <0.05 level (fig. 4) . During this 5-year period we have witnessed the re surgence of radical surgery for the control of localized disease: 3 radical prostatectomies were performed in 1987, while 22 were
349
C H ANGING TREND S IN MANAGEMENT OF PROSTATIC DISEASE
by the respondents was the use of medical therapy for the prevention and treatment of BPH. 3 Lepor et al recently reviewed the literature on alternatives to trans urethral prostatectomy, specifically a-adrenergic block ade. 8 Of 17 studies 15 attest to the efficacy of compounds, such as dibenzyline, prazosin or terazosin, in improving voiding function. Treatment with transurethral prostatectomy results in greater than 100% improvement in symptom scores followed by transurethral incision (82% improvement) and a-blockade therapy (5 1% improvement). However, transurethral prostatec tomy has a known high incidence of morbidity8 and averages a D ISCUSSION In 1976 the Society of University Urologists commissioned a 1-time cost of $ 12,000. In a survey of American urologists in 1986, Holtgrewe et al nationwide survey in which urologists were asked to predict found that transurethral prostatectomy, the "dominant opera future changes and trends in the practice of urology during the tion in American urology," accounted for 38% of all major subsequent 10 to 30 years. The most popular responses were 5 an increase in endourological procedures, more government urological operations performed. However, the number of transurethral prostatectomies performed each year per re intervention, advances in microsurgical techniques, cure of spondent has decreased from 101 in 1962 to 76 in 1972 to 67 in cancer by nonoperative means, mounting public hostility to physicians and the development of a residency matching pro 1986. During the same period, the number of benign open prostatectomies decreased from 20 per year in 1962 to 6 in gram for urology. However, the most popular prediction offered 1986. Our data from 1987 to 1991 are even more dramatic. The o f c a n c e r pts treated/y r national study by Holtgrewe et al documents a 33 % diminution �--------------------20 % ------, during 14 years in the number of transurethral prostatectomies performed per year. 5 Our decrease is approximately 75 % during L H RH a period a third as long and is statistically significant (p 15 <0.005, fig. 3). We further examine the breakdown of all of our major procedures during the first and last years of the 5-year 10 study period. In 1991 radical prostatectomy constituted 37% of all of our major procedures and transurethral prostatectomy 5 comprised only 14% (fig. 6), which is essentially a reversal of the statistics for 1987 (fig. 5). Performance of fewer radical cystectomies accounts for the slight decrease in "neoplasm 0 1991 1990 other" surgery, presumably due to the demonstrated efficacy of 1989 1988 1987 intravesical immunotherapy. YEAR Interestingly, all 3 partners in the practice have performed a T h e rapy diminishing number of transurethral prostatectomies; the per cent decline is consistent among them (p >0.05). -«-- L H R H a n al o g -+- D E S - Orc h i e cto m y Cooner et al, 2 and Kaufman and Schultz1 3 demonstrated the FIG. 4. Yearly comparison of use of hormonal agents for dissemi use of combining PSA, digital rectal examination and transrec nated disease. DES, diethylstilbestrol. LHRH, luteinizing hormone tal ultrasound-guided biopsy for early diagnosis of prostate releasing hormone. cancer. They calculated that digitally directed biopsy would have missed 20 to 67 of the 203 palpable tumors and all of the P r o s t a t e - b e n i g n 4 0% impalpable lesions in their studies. 2 • Similarly, transrectal ultrasound-guided biopsy is our method of choice for prostate biopsy, for palpable and impalpable lesions, having replaced Pros t ate-ma l i g na n t 8% transrectal aspiration cytology and transperineal core biopsy. Of all our biopsies in 1991, 28% were driven by elevated P SA levels in the face of a normal digital rectal examination and Other 4% half of these patients had biopsy proved cancer that presumably P e d i a t r i cs 4 % would not have been diagnosed until much later. N e o p l asm-ot her 22% Fe m a l e 3 % Largely due to PSA and transrectal ultrasound, and the diminishing number of transurethral prostatectomies per Cal c u l us 1 4 % formed for benign disease, only 3% of our patients in 1991 were diagnosed with prostate cancer during transurethral resection, FIG. 5. Breakdown o f major procedures during 1987 agreeing with similar results discussed by Bagshaw et al in 5 P ros t a t e - ma l i g n a n t 3 7 % 1990. We also noted a significant decrease in the percentage of patients who presented with a nodule, from 9% of all patients in 1987 to 3% in 1991. In patients ultimately diagnosed with P r o s tate-be n i g n 1 4 % cancer, presentation with a nodule decreased from 25% in 1988 to 13% in 1991. Elevated PSA level has currently surpassed nodule and prostatism as the leading complaint of cancer Other 3% patients, since the percentage of patients with cancer in our Pe d i at r i cs 6 % series has grown (fig. 2). These trends, aided by PSA and transrectal ultrasound, are largely due to the discovery of more cancers at earlier stages before they attain palpable features on I n fer t i l i t y / e r ec t i l e 5 % digital rectal examination. Cal culus 10% In this atmosphere of desirability for minimally invasive intervention it is somewhat surprising that radical prostatecFIG. 6. Breakdown o f major procedures during 1991
performed in 1991. This 6-fold increase is significant at p <0.005. Finally, we present our breakdown of major procedures per formed by the practice in the first and last years of the study period (figs. 5 and 6, respectively). The most pronounced changes are noted in the groups prostate-malignant, which includes radical prostatectomy, and prostate-benign, which in cludes transurethral prostatectomy and open prostatectomy.
1
1
1
14
350
CHANGING TRENDS IN MANAGEMENT OF PROSTATIC DISEASE
tomy has gained such a stronghold as demonstrated in our study. This undoubtedly represents our bias as urological sur geons, as well as reflects familiarity with recent nerve sparing modifications, and our patients desire to be truly tumor-free. In addition, the increase in the number of patients who undergo radiation therapy is probably representative of the absolute increase in numbers of patients diagnosed with cancer at a more advanced age more than it is secondary to urologist and patient preferences. In a study of the data from 13 institutions Cassileth et al asked 159 patients with untreated stage D prostate cancer to choose between a luteinizing hormone-releasing hormone ana logue and orchiectomy. 1 6 Of the patients 78% chose the lutein izing hormone-releasing hormone analogue. Avoidance of sur gery was the most popular reason for nonoperative therapy, while convenience was the reason most often chosen for or chiectomy. 1 6 In a European trial 86% of the patients chose the luteinizing hormone-releasing hormone analogue. 17 For lutein izing hormone-releasing hormone analogues, multiple studies here and in Europe have demonstrated therapeutic equivalence to orchiectomy, and the increased morbidity and mortality rates of estrogens in comparison. 18-21 Although not yet significant, our data reflect similar trends with the increasing popularity of monthly injections of a lu teinizing hormone-releasing hormone analogue, with or without flutamide. However, the annual cost of these pharmaceuticals is between $2,000 and $4,000 each, 8 while orchiectomy has a 1time expense approximating $2,000. The administration of estrogens, while achieving comparable hormonal ablation, has fallen into current disfavor (fig. 4) due to observed risks of cardiovascular morbidity. Prominent local media coverage of nonoperative alternatives for BPH treatment, coinciding with published reports regarding the morbidity of transurethral prostatectomy and the risks of blood transfusions, have caused urologists and patients to opt initially for more conservative, medical therapy. The wide spread use of PSA by internists and urologists coupled with the ease of transrectal ultrasound has greatly increased the impetus for early diagnosis of prostate cancer. Patient preferences in our geographic area for nonoperative treatment in the face of metastatic or high risk disease and third party reimbursement have led to the popularity of luteinizing hormone-releasing hormone analogues and antiandrogen compounds. Only in the treatment of localized prostate cancer has the surgical option prevailed as that currently most desirable for the patient and urologist. Our practice is largely drawn from an affluent, med ically knowledgeable population that, indeed, may not reflect the composition of similar sized samples from other parts of our diverse metropolitan area, as well as other more distant geographic regions. During the course of this study we have witnessed dramatic changes in the management of prostatic disease in our urological practice, which reflect local trends and possibly predict future national tendencies. Interestingly, an analysis of the financial impact of these major changes to date has failed to demonstrate an adverse effect on practice income. REFERENCES
1. Optenberg, S. A. and Thompson, I. M.: Economics of screening for carcinoma of the prostate. Urol. Clin. N. Amer., 1 7: 719, 1990. 2. Austenfeld, M. S. and D avis, B. E.: New concepts in the treatment
3. 4. 5. 6. 7.
8. 9. 10. 11. 12.
13. 14. 15. 16. 17. 18. 19. 20.
21.
of stage Dl adenocarcinoma of the prostate. Urol. Clin. N. Amer., 17: 867, 1990. Zinner, N. R., Enzer, S., Brosman, S. A., Corriere, J. N. and Hinman, F., Jr.: Forecasts of change in urology. Delphi Future Study, Society of University Urologists. Urology, 37: 491, 1991. Schmidt, J. D., Mettlin, C. J., Natarajan, N., Peace, B . B., Beart, R. W., Jr., Winchester, D. P. and Murphy, G. P.: Trends in patterns of care for prostatic cancer, 1974-1983: results of surveys by the American College of Surgeons. J. Urol., 136: 416, 1986. Holtgrewe, H. L., Mebust, W. K., Dowd, J. B., Cockett, A. T. K., Peters, P. C. and Proctor, C.: Transurethral prostatectomy: practice aspects of the dominant operation in American urology. J. Urol., 1 4 1 : 248, 1989. Mebust, W. K. and Holtgrewe, H. L.: Current status of transure thral prostatectomy. A review of the AUA National Cooperative Study. World J. Urol., 6: 194, 1989. Mebust, W. K., Holtgrewe, H. L., Cockett, A. T. K., Peters, P. C. and Writing Committee: Transurethral prostatectomy: immedi ate and postoperative complications. A cooperative study of 13 participating institutions evaluating 3,885 patients. J. Urol., 141: 243, 1989. Lepor, H., Knapp-Maloney, G. and Sunshine, H.: A dose titration study evaluating terazosin, a selective, once-a-day al-blocker for the treatment of symptomatic benign prostatic hyperplasia. J. Urol., 144: 1393, 1990. Silverberg, E. and Lubera, J. A.: Cancer statistics, 1989. CA, 39: 3, 1989. Resnick, M. I.: Evaluation of prostatic carcinoma: noninvasive and preoperative techniques. Prostate, 1 : 311, 1980. Mettlin, C., Lee, F., Drago, J. and Murphy, G. P.: The American Cancer Society National Prostate Cancer Detection Project. Findings on the detection of early prostate cancer in 2425 men. Cancer, 67: 2949, 1991. Cooner, W. H., Mosley, B. R., Rutherford, C. L., Jr., Beard, J. H., Pond, H. S., Terry, W. J., Igel, T. C. and Kidd, D. D.: Prostate cancer detection in a clinical urological practice by ultrasonog raphy, digital rectal examination and prostate specific antigen. J. Urol., 143: 1146, 1990. Kaufman, J. J. and Schultz, J. I.: Needle biopsy of the prostate: a reevaluation. J. Urol., 87: 164, 1962. Rifkin, M. D., Kurtz, A. B. and Goldberg, B. B.: Prostate biopsy utilizing transrectal ultrasound guidance: diagnosis of nonpal pable cancers. J. Ultrasound Med., 2 : 165, 1983. Bagshaw, M. A., Cox, R. S. and Ramback, J. E.: Radiation therapy for localized prostate cancer. Justification by long-term follow up. Urol. Clin. N. Amer., 17: 787, 1990. Cassileth, B. R., Soloway, M. S., Vogelzang, N. J., Schellhammer, P. S., Seidmon, E. J., Hait, H. I. and Kennealey, G. T.: Patients ' choice of treatment in stage D prostate cancer. Urology, suppl. 5, 33: 57, 1989. Lunglmayr, G. and Girsch, E.: Patient choice in the treatment of advanced prostate cancer. Roy. Soc. Med. Serv. Int. Congr. Symp. Ser., 125:· 47, 1987. Johansson, J.-E., Andersson, S.-0., Holmberg, L. and Bergstrom, R.: Primary orchiectomy versus estrogen therapy in advanced prostatic cancer-a randomized study: results after 7 to 10 years of followup. J. Urol., 145: 519, 1991. Sharifi, R., Soloway, M. and The Leuprolide Study Group: Clinical study of leuprolide depot formulation in the treatment of ad vanced prostate cancer. J. Urol., 143: 68, 1990. Soloway, M. S., Chodak, G., Vogelzang, N. J., Block, N. L., Schellhammer, P. F., Smith, J. A., Jr., Scott, M., Kennealey, G. and Gau, T. C.: Zoladex versus orchiectomy in treatment of advanced prostate cancer: a randomized trial. Zoladex Prostate Study Group. Urology, 37: 46, 1991. Peeling, W. B.: Phase III studies to compare goserelin (Zoladex) with orchiectomy and with diethylstilbestrol in treatment of prostatic carcinoma. Urology, suppl. 5, 33: 45, 1989.
Vol. 150, 347-350,
INC
Printed
1993
[l. S. A.
CHANGING TRENDS IN THE MANAGEMENT OF PHOSTATIC DISEASE IN A SINGLE PRIVATE PRACTICE: A 5-YEAR FOLLOWUP DAVID S. BRESLIN, EDWARD C . MUECKE, JON M. RECKLER AND JOHN A. FRACCHIA From the Section of Urology, Lenox Hill Hospital, New York, New York
ABSTRACT
Evaluation and management services provided by the practicing urologist have changed dramat ically during the last few years. This is particularly evident in the approach to men with bladder outlet symptoms and in those in whom the diagnosis of prostate cancer is a distinct possibility. The impact of medical management/observation of symptomatic benign prostatic hypertrophy, as well as the influence of prostate specific antigen, transrectal ultrasound and biopsy, radical prostatectomy and hormonal agents in a 3-man private clinical practice is analyzed. The records of 2,206 patients new to the practice who presented with a variety of prostate-related complaints from July 1, 1986 to June 30, 1991 were reviewed. Of these patients 1 ,822 (82 % ) were evaluated for presumed benign bladder outlet symptoms. During year 1 of the study, ending on June 30, 1987, 28% of the presumed benign prostatic hypertrophy patients were treated with transurethral prostatectomy, compared to only 8% of such p atients in 199 1 . In contrast, ()'-blocking agents were used to treat 21 % of these patients in 1 99 1 . Transrectal ultrasound biopsy currently accounts for 87% of all prostatic biopsies, increasing 4-fold during 5 years. Radical prostatectomy has increased 6-fold during the course of the study. Administration of a luteinizing hormone-releasing hormone analogue has supplanted orchiectomy and estrogen therapy for the treatment of disseminated disease, as witnessed by a 4fold increase in its use. While it is recognized that these trends are presently applicable to our local metropolitan region, they may reflect practice patterns in similar demographic groups, as well as predict future tendencies nationwide. KEY WORDS: benign prostatic hypertrophy, prostatic neoplasms
From 1980 to 1990 the percentage of men in the United States who were older than 65 years increased approximately 25% over a similar cohort during the previous decade. 1 Cur rently, there are 25 million men in this country older than 50 years and this number is projected to double by the year 2010. 2 Diseases of the prostate, benign and malignant, account for significant health care expenditures in this expanding elderly male population. Because of its relative importance to the practice of urology, various studies have examined practice trends for the management of prostatic disease, particularly benign prostatic hypertrophy (BPH) and cancer. 3 • Transurethral resection of the prostate for BPH is one of the most commonly performed operations in the United States. 5 · For the last several decades this operation has been the most frequent modality for definitive alleviation of bladder outlet obstruction secondary to benign and malignant processes, 7• and it remains the dominant operation in American urological practice. 5 However, alternative options, including watchful waiting as well as the use of specific al-adrenergic blockers, the impending use of hormonal blockade and less invasive procedures, such as transurethral incision, balloon dilation, prostate hyperthermia, intraprostatic coils, laser ablation and so forth, have challenged the role of prostatectomy in the management of benign bladder outlet obstruction. Carcinoma of the prostate remains the most commonly di agnosed male malignancy and accounts for the second highest male cancer death rate. 9 Earlier diagnosis and an aging popu lation are factors increasing the incidence and mortality rates: in the United States approximately 122,000 men will be diag nosed this year 10 and approximately 32,000 will die. 11 Prostate specific antigen (PSA) has become the most useful tumor marker in clinical oncology and may help to identify many patients with subclinical disease. Discovery of elevated serum PSA levels coupled with transrectal ultrasound and 4
biopsy have facilitated earlier diagnosis of prostate cancer. The technique of radical prostatectomy has been refined, and has become an effective, safe method to treat localized carcinoma in selected patients. The use of depot injections of a luteinizing hormone-releasing hormone analogue for patients with met astatic and high risk disease is currently an established treat ment modality. In an effort to assess some of the impact of the aforementioned advances and in an attempt to document future trends in urological practice, we have examined the records of all new patients older than 50 years with prostate-related complaints seen by a 3-man urban private practice during a recent 5 year period ending June 30, 1991.
6
8
Accepted for publication January 22, 1993. Supported in part by a grant from Abbott Laboratories.
347
MATERIALS AND METHODS
The records of all 2,206 new patients older than 50 years old with prostate-related complaints entering a 3-man urology practice between July 1, 1986 and June 30, 1991 were reviewed. Patients were physician-referred or self-referred for a variety of complaints, such as prostatism, prostate nodule assessed by digital rectal examination, elevated serum PSA level or pros tatitis. A number of patients were seen for additional opinions of carcinoma previously diagnosed elsewhere. Routine demographic data were recorded as well as clinical information pertinent to that evaluation, treatment and fol lowup. Initial and subsequent PSA and acid phosphatase levels, when applicable, were documented. The results of digital rectal examination offered an estimation of prostate size and the presence or absence of suspicious features. Patients with presumed benign bladder outlet obstruction and prostatism were managed expectantly, medically or sur gically. Medical management included administration of al adrenergic blockers (dibenzyline , prazosin or terazosin) and/or compounds administered to relieve irritative symptoms, such as oxybutynin, flavoxalate, phenazopyridine and so forth. Pa tients with presumed infectious complaints were treated with
348
CHANGING TRENDS IN MANAGEMENT O F PROSTATIC DISEASE
antimicrobial agents. Surgical therapy included transurethral prostatectomy or open prostatectomy. PSA was assayed with the Hybritech monoclonal method. Transrectal ultrasound of the prostate was performed with a Bruel & Kjaer No. 1846 scanner and a Type 8851 7.0 MHz. probe. Biopsies were performed by digitally directed fine-needle aspiration and histological core sampling or transrectal ultra sound-guided biopsy. The treatment offered to each patient with malignant disease was registered. Options included transurethral resection, radi cal prostatectomy, radiation therapy, hormonal manipulation and observation. Pathological stage was applied to patients undergoing radical prostatectomy. Data were analyzed for significance with the chi-square sta tistic. P values �0.05 infer statistically significant trends in our comparison of the information on a year to year basis. The data are analyzed and reported as percentage of patients per group per year, rather than in absolute numbers, because the number of patients in the individual groups, as well as the total for each year, was not identical. We compared the various changes and trends in our methods of diagnosis and manage ment for each year ending June 30, as described previously. RESULTS
The charts of 2,206 men older than 50 years who were new to the practice with prostate-related complaints were studied (mean 441 per year, range 375 to 477 per year). This group comprised 59% of all new patients who were evaluated by the practice during the 5-year period. Average patient age was 68 years, which showed no significant change during the course of the study (p >0.05) . Patients presented with 1 of 6 different complaints (fig. 1 ) . Prostatism decreased from a high of 389 patients (82 % ) in 1989 to 271 (72 % ) and 296 (67 % ) patients in 1990 and 1991, respectively (p <0.05). Elevated PSA level as a
P R O S TAT E CH ECK 3 % P ROSTAT I T I S 5 %
E L E V P S A 5% N O D U L E 6%
FIG. 1 . Breakdown o f presenting complaint fo r 2,206 patients be tween 1987 and 1991. ELEV, elevated levels. of P ts / y r ---------- - - - ------40 %
--�
30 20 10 0
1987
1988
1989
YEAR
1990
1991
Complaint
1111 N o d u le
� Prostat ism
D E lev PSA
FIG. 2. Comparison of presenting complaint in cancer patients
(Pts. ) . Elev, elevated levels.
35
% of B P H pts/yr
30 25 20 15 10 5 0
1987
1988
- TURP
1989
1990
1991
YEAR � A l p h a b lockade
FIG. 3. Annual comparison of patients treated with transurethral prostatectomy ( TURP) versus a-blockade.
referring complaint increased 300% (60 patients in 1991) during the course of the study (p <0.005) and is currently the leading presenting complaint for patients who are ultimately diagnosed with cancer (fig. 2). Presentation with the complaint of a palpable nodule decreased 67% during 5 years, from 9 % of all patients in 1987 to 3% of all patients in 1991 (p <0.005) . A total o f 1 ,822 patients was evaluated for benign bladder outlet symptoms during the 5 years of the study. In the initial study year (ending June 30, 1987) 28% of 348 patients with BPH were treated with transurethral resection of the prostate, compared to only 8% (29 patients) during the last year (ending June 1991, fig. 3 ) . This 73% decrease in the yearly number of transurethral resections was significant at the p <0.005 level. In fact, all 3 partners in this group performed fewer transure thral resections without significant difference among them (p >0.05). In contrast, 76 BPH patients ( 2 1 %) were managed in 1991 with 1 of the various a-blocking agents (p <0.005, fig. 3). (Such agents were not used routinely during the earlier years of this study.) A total of 384 new patients was evaluated for various stages of prostate cancer throughout the 5 years of the study. At a statistically meaningful level (p <0.0 1 ) , the percentage of pa tients with cancer is increasing, ranging from 14% of all pa tients in 1988 to 21 % in 1990. In 1991 transrectal ultrasound-guided biopsy accounted for 87% of all prostate biopsies (56 patients) in this practice, increasing by greater than 400% during 5 years (p <0.005 ) . In 1987 digitally directed aspiration cytology and/or transperineal core histological biopsies accounted for 90% of all tissue sam pling, while in 1991 only 13% of all patients were so biopsied. Transurethral resection diagnosed 24 cancers (38% ) in 1 987 and only 2 (3%) in 1991. Illustrating the recent influence of PSA, only 2% of the patients who underwent biopsy in 1987 did so solely for an elevation of PSA (with a normal digital rectal examination), while 28% of 1 1 1 biopsies in 1991 were performed for this a reason (p <0.005) . Use o f external radiation therapy as primary treatment has increased by more than 100% during the 5 years (p <0.005) . The use o f brachytherapy has remained constant and low in our practice. Administration of luteinizing hormone-releasing hormone analogues has grown by a multiple of 4 from 1987 to 1991 (14 patients in 1991, p <0.005) , while orchiectomy for androgen ablation has become much less popular (2 patients in 1991, fig. 4). Estrogen administration has diminished by 600% between 1987 and 1991 but, due to overall small numbers, this decreasing tendency is not yet significant at the p <0.05 level (fig. 4) . During this 5-year period we have witnessed the re surgence of radical surgery for the control of localized disease: 3 radical prostatectomies were performed in 1987, while 22 were
349
C H ANGING TREND S IN MANAGEMENT OF PROSTATIC DISEASE
by the respondents was the use of medical therapy for the prevention and treatment of BPH. 3 Lepor et al recently reviewed the literature on alternatives to trans urethral prostatectomy, specifically a-adrenergic block ade. 8 Of 17 studies 15 attest to the efficacy of compounds, such as dibenzyline, prazosin or terazosin, in improving voiding function. Treatment with transurethral prostatectomy results in greater than 100% improvement in symptom scores followed by transurethral incision (82% improvement) and a-blockade therapy (5 1% improvement). However, transurethral prostatec tomy has a known high incidence of morbidity8 and averages a D ISCUSSION In 1976 the Society of University Urologists commissioned a 1-time cost of $ 12,000. In a survey of American urologists in 1986, Holtgrewe et al nationwide survey in which urologists were asked to predict found that transurethral prostatectomy, the "dominant opera future changes and trends in the practice of urology during the tion in American urology," accounted for 38% of all major subsequent 10 to 30 years. The most popular responses were 5 an increase in endourological procedures, more government urological operations performed. However, the number of transurethral prostatectomies performed each year per re intervention, advances in microsurgical techniques, cure of spondent has decreased from 101 in 1962 to 76 in 1972 to 67 in cancer by nonoperative means, mounting public hostility to physicians and the development of a residency matching pro 1986. During the same period, the number of benign open prostatectomies decreased from 20 per year in 1962 to 6 in gram for urology. However, the most popular prediction offered 1986. Our data from 1987 to 1991 are even more dramatic. The o f c a n c e r pts treated/y r national study by Holtgrewe et al documents a 33 % diminution �--------------------20 % ------, during 14 years in the number of transurethral prostatectomies performed per year. 5 Our decrease is approximately 75 % during L H RH a period a third as long and is statistically significant (p 15 <0.005, fig. 3). We further examine the breakdown of all of our major procedures during the first and last years of the 5-year 10 study period. In 1991 radical prostatectomy constituted 37% of all of our major procedures and transurethral prostatectomy 5 comprised only 14% (fig. 6), which is essentially a reversal of the statistics for 1987 (fig. 5). Performance of fewer radical cystectomies accounts for the slight decrease in "neoplasm 0 1991 1990 other" surgery, presumably due to the demonstrated efficacy of 1989 1988 1987 intravesical immunotherapy. YEAR Interestingly, all 3 partners in the practice have performed a T h e rapy diminishing number of transurethral prostatectomies; the per cent decline is consistent among them (p >0.05). -«-- L H R H a n al o g -+- D E S - Orc h i e cto m y Cooner et al, 2 and Kaufman and Schultz1 3 demonstrated the FIG. 4. Yearly comparison of use of hormonal agents for dissemi use of combining PSA, digital rectal examination and transrec nated disease. DES, diethylstilbestrol. LHRH, luteinizing hormone tal ultrasound-guided biopsy for early diagnosis of prostate releasing hormone. cancer. They calculated that digitally directed biopsy would have missed 20 to 67 of the 203 palpable tumors and all of the P r o s t a t e - b e n i g n 4 0% impalpable lesions in their studies. 2 • Similarly, transrectal ultrasound-guided biopsy is our method of choice for prostate biopsy, for palpable and impalpable lesions, having replaced Pros t ate-ma l i g na n t 8% transrectal aspiration cytology and transperineal core biopsy. Of all our biopsies in 1991, 28% were driven by elevated P SA levels in the face of a normal digital rectal examination and Other 4% half of these patients had biopsy proved cancer that presumably P e d i a t r i cs 4 % would not have been diagnosed until much later. N e o p l asm-ot her 22% Fe m a l e 3 % Largely due to PSA and transrectal ultrasound, and the diminishing number of transurethral prostatectomies per Cal c u l us 1 4 % formed for benign disease, only 3% of our patients in 1991 were diagnosed with prostate cancer during transurethral resection, FIG. 5. Breakdown o f major procedures during 1987 agreeing with similar results discussed by Bagshaw et al in 5 P ros t a t e - ma l i g n a n t 3 7 % 1990. We also noted a significant decrease in the percentage of patients who presented with a nodule, from 9% of all patients in 1987 to 3% in 1991. In patients ultimately diagnosed with P r o s tate-be n i g n 1 4 % cancer, presentation with a nodule decreased from 25% in 1988 to 13% in 1991. Elevated PSA level has currently surpassed nodule and prostatism as the leading complaint of cancer Other 3% patients, since the percentage of patients with cancer in our Pe d i at r i cs 6 % series has grown (fig. 2). These trends, aided by PSA and transrectal ultrasound, are largely due to the discovery of more cancers at earlier stages before they attain palpable features on I n fer t i l i t y / e r ec t i l e 5 % digital rectal examination. Cal culus 10% In this atmosphere of desirability for minimally invasive intervention it is somewhat surprising that radical prostatecFIG. 6. Breakdown o f major procedures during 1991
performed in 1991. This 6-fold increase is significant at p <0.005. Finally, we present our breakdown of major procedures per formed by the practice in the first and last years of the study period (figs. 5 and 6, respectively). The most pronounced changes are noted in the groups prostate-malignant, which includes radical prostatectomy, and prostate-benign, which in cludes transurethral prostatectomy and open prostatectomy.
1
1
1
14
350
CHANGING TRENDS IN MANAGEMENT OF PROSTATIC DISEASE
tomy has gained such a stronghold as demonstrated in our study. This undoubtedly represents our bias as urological sur geons, as well as reflects familiarity with recent nerve sparing modifications, and our patients desire to be truly tumor-free. In addition, the increase in the number of patients who undergo radiation therapy is probably representative of the absolute increase in numbers of patients diagnosed with cancer at a more advanced age more than it is secondary to urologist and patient preferences. In a study of the data from 13 institutions Cassileth et al asked 159 patients with untreated stage D prostate cancer to choose between a luteinizing hormone-releasing hormone ana logue and orchiectomy. 1 6 Of the patients 78% chose the lutein izing hormone-releasing hormone analogue. Avoidance of sur gery was the most popular reason for nonoperative therapy, while convenience was the reason most often chosen for or chiectomy. 1 6 In a European trial 86% of the patients chose the luteinizing hormone-releasing hormone analogue. 17 For lutein izing hormone-releasing hormone analogues, multiple studies here and in Europe have demonstrated therapeutic equivalence to orchiectomy, and the increased morbidity and mortality rates of estrogens in comparison. 18-21 Although not yet significant, our data reflect similar trends with the increasing popularity of monthly injections of a lu teinizing hormone-releasing hormone analogue, with or without flutamide. However, the annual cost of these pharmaceuticals is between $2,000 and $4,000 each, 8 while orchiectomy has a 1time expense approximating $2,000. The administration of estrogens, while achieving comparable hormonal ablation, has fallen into current disfavor (fig. 4) due to observed risks of cardiovascular morbidity. Prominent local media coverage of nonoperative alternatives for BPH treatment, coinciding with published reports regarding the morbidity of transurethral prostatectomy and the risks of blood transfusions, have caused urologists and patients to opt initially for more conservative, medical therapy. The wide spread use of PSA by internists and urologists coupled with the ease of transrectal ultrasound has greatly increased the impetus for early diagnosis of prostate cancer. Patient preferences in our geographic area for nonoperative treatment in the face of metastatic or high risk disease and third party reimbursement have led to the popularity of luteinizing hormone-releasing hormone analogues and antiandrogen compounds. Only in the treatment of localized prostate cancer has the surgical option prevailed as that currently most desirable for the patient and urologist. Our practice is largely drawn from an affluent, med ically knowledgeable population that, indeed, may not reflect the composition of similar sized samples from other parts of our diverse metropolitan area, as well as other more distant geographic regions. During the course of this study we have witnessed dramatic changes in the management of prostatic disease in our urological practice, which reflect local trends and possibly predict future national tendencies. Interestingly, an analysis of the financial impact of these major changes to date has failed to demonstrate an adverse effect on practice income. REFERENCES
1. Optenberg, S. A. and Thompson, I. M.: Economics of screening for carcinoma of the prostate. Urol. Clin. N. Amer., 1 7: 719, 1990. 2. Austenfeld, M. S. and D avis, B. E.: New concepts in the treatment
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