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Collagen injection or artificial sphincter for postprostatectomy incontinence: collagen1
EDITORIAL
COLLAGEN INJECTION OR ARTIFICIAL SPHINCTER FOR POSTPROSTATECTOMY INCONTINENCE: COLLAGEN R. DUANE CESPEDES
T
he nature of this debate would suggest that collagen injection therapy and the artificial urinary sphincter (AUS) are competitive therapies and that only one procedure should be used at the exclusion of the other. In actuality, these therapies are complementary, each one being useful for selected groups of patients. When performing collagen injections, as with any procedure, proper patient selection and the establishment of optimal methods of treatment delivery are crucial for therapeutic success and patient satisfaction. At the time of Food and Drug Administration approval in December 1993, there was little information regarding this, and unfortunately, many patients subsequently “failed” collagen injection therapy because of this lack of data. Thereafter, many physicians were reluctant to treat patients with collagen, and some have since concluded that collagen injection therapy simply does not work for postprostatectomy incontinence (PPI). Recent data would suggest that collagen injection therapy does indeed work well in properly selected patients when the injections are performed according to the methods developed and perfected during the past few years. The data pertaining to proper patient selection are perhaps the most important gathered thus far. A study from 1996 noted that in postprostatectomy patients who used fewer than six pads per day, 72% were dry or significantly improved at 7 months after injection; only 29% of patients using more than six pads per day were dry.1 Additionally, patients who used fewer than three pads per day were dry or significantly improved in more than 80% of cases. Poor prognostic factors included postopera-
The opinions contained herein are those of the authors and are not to be construed as reflecting the views of the Air Force or the Department of Defense. From the Department of Urology, Wilford Hall Medical Center, Lackland Air Force Base, Texas Reprint requests: R. Duane Cespedes, M.D., Female Urology and Urodynamics, Department of Urology (MMKU), Wilford Hall Medical Center, Lackland Air Force Base, TX 78236 Submitted: July 2, 1999, accepted (with revisions): August 31, 1999 PUBLISHED BY ELSEVIER SCIENCE INC.
tive radiation therapy, adjuvant cryotherapy, and vigorous bladder neck incisions. In the study, the patients rendered dry required a mean of 4.2 injections and 29 mL of collagen. Smith and colleagues2 reported a 38% overall cure rate in 54 patients with a mean follow-up of 29 months; however, in the group of patients who used three pads a day or less, they found a 50% cure rate. Patients rendered dry required a mean of four injections and 20.0 mL of collagen. Bevan-Thomas and colleagues3 recently reported their long-term data of 257 patients after prostatectomy, with a mean follow-up of 28 months. They found that 20% of patients were dry and an additional 39% were significantly improved, for an overall 59% dry or significantly improved rate. Patients who had milder degrees of incontinence and had not received adjuvant radiation or bladder neck incision fared better. A mean of 4.4 injections and 36 mL of collagen were used to obtain dryness in these patients. In a recent study4 focusing on the preoperative evaluation, the abdominal leak point pressure (ALPP) was found to be predictive of postoperative success when using collagen injection therapy. Sanchez-Ortiz and colleagues4 found that patients with a preoperative ALPP greater than 60 cm H2O were cured in 70% of cases, and those with an ALPP less than 60 cm H2O had a 19% cure rate. The data emanating from these studies confirm that the best results can be obtained by selecting patients with milder degrees of incontinence and a preoperative ALPP greater than 60 cm H2O. Important procedural techniques have also been learned from these studies. It is clear that the technique of injecting smaller quantities (2.5 to 7.5 mL) of collagen at longer intervals (greater than 4 weeks) and giving a minimum of four injections yields better cure rates. What this means is that published studies in which an average of two or three injections were given are of little clinical value. Transient but significant improvement after the first or second injection is not a cause for disappointment, as these patients will usually have a good result if additional injections are performed. UROLOGY 55: 5–7, 2000 PII S0090-4295(99)00418-5 5
In similar fashion, if a durable and significant improvement is noted after three or four injections, it is likely that further injections will yield further improvement in continence. Calling the procedure a failure when significant improvement is not observed after one or two injections does not constitute an adequate trial. A common clinical scenario involves the patient with PPI who initially desires collagen injection therapy, but after one or two injections have been performed in the operating room with little improvement and significant expense, considers the procedure a failure and an AUS is recommended. Consequently, if the patient is unwilling to undergo a minimum of four injections and wait the time necessary to perform them, it is probably better to undergo some other form of therapy, as injecting collagen once or twice and subsequently changing or stopping therapy is wasteful of time and money. Although most investigators have performed collagen injections using a retrograde, transurethral route, some investigators have reported good results using a transvesical antegrade approach. Wainstein and Klutke5 reported an encouraging 25% dry and 45% significantly improved rate at a mean 8.5 months of follow-up in their postprostatectomy population. Appell and colleagues6 also observed an encouraging 75% dry rate in their patients after 6 months of follow-up. At the 12-month follow-up evaluation, the “cure rate” had decreased to 37.5%; however, continence presumably would have been restored after an additional injection. Other aspects of collagen injection therapy that appear to be important for therapeutic success but are more difficult to quantify include the degree of tissue scarring, the length of the suprasphincteric urethra, surgeon experience, and the use of specialized injection equipment. Although specialized equipment is not required for injecting collagen, the ease of administration, collagen wastage, and overall results appear to be improved when it is used. Another important question answered by these early studies was, how often will reinjection be necessary after continence is achieved? Since not all patients rendered dry have required reinjection, the range is not known; however, Smith and colleagues2 found that of their patients who became continent, 60.9% were dry at 1 year and 42.8% were dry at 2 years. Another study with 36 dry patients noted that at 6 months after injection, only 1 patient required one additional injection to regain continence.1 Note that the requirement for periodic collagen reinjection can also bias longterm data, since some patients initially rendered dry with collagen who subsequently develop recurrent incontinence may be considered a “failure” 6
when in fact the patient simply needs another collagen injection. The cost-effectiveness of collagen injection therapy has also become a controversial issue. Some reports have concluded that collagen injection therapy, when compared with the AUS, is not cost effective.7,8 In these studies, injections were performed in the operating room using a limited number of injections, with resulting poor cure rates. A cost-effectiveness study comparing two combined AUS series with collagen injections performed in the office using Medicare reimbursement has been performed.9 –11 That study found that collagen injection therapy cost $6021 and the AUS cost $11,933 to achieve comparable levels of continence when a sufficient number of injections were given using the techniques described above. When the long-term (10 years) management costs of treatment, potential reinjections, surgical revisions, and failures in each group were factored into the equation, the total cost in the collagen group was $7884, and the projected total cost in the AUS group was $16,103. A recent report by Brown and colleagues12 presented data that further support the cost-effectiveness of collagen injections when compared with both the AUS and conservative therapy. Overall, collagen appears to be more costeffective than an AUS in the postprostatectomy patient with mild to moderate incontinence when injections are performed in the clinic. Although the AUS is also an excellent choice for the treatment of PPI in properly selected patients, it too has its drawbacks. A careful review of 50 patients who received an AUS for PPI highlights the long-term results of placing an AUS.13 At a mean follow-up of 23 months, the investigators found that only 20% of patients were completely dry, 50% leaked urine on a daily basis, and 24% of patients wore an average of 1.5 pads per day. Additionally, surgical revisions were necessary in 26% of patients. A more recent review of 323 patients who received an AUS with a minimum follow-up of 18 months revealed a similar 27% reoperation rate for mechanical and nonmechanical reasons.14 Despite these results and the need for revisions, most patients were satisfied with the device. The quality of life is undoubtedly improved in most patients after AUS placement because of the dramatic improvement in continence within a very short time; however, collagen does not have that luxury, since it requires multiple injections for a longer period, and the improvements are much more gradual. Finally, in addition to the initial expense of the AUS and the inherent morbidity of an operation, one must consider the significant cost and morbidity of surgical revisions. The decision to proceed with either collagen injection therapy or an AUS must be tempered by an UROLOGY 55 (1), 2000
understanding of the comparative risks and benefits, treatment costs, and long-term complications and requirements of both modalities. Consequently, who is the ideal candidate for collagen injection therapy? The ideal candidate for collagen injection therapy is a patient who uses three pads or fewer per day, has adequate suprasphincteric length for injection, has an ALPP greater than 60 cm H2O, and has not undergone postoperative radiation therapy, cryotherapy, or bladder neck incision. Additionally, the patient must be willing to undergo multiple injections during a prolonged period, with the knowledge that if dryness is achieved, periodic reinjections will be required to maintain it. With the decreasing age of the prostatectomy patient, improvements in surgical techniques, and the inherent desire to avoid surgery, many patients will fulfill these criteria. Which patients are candidates to receive an AUS as the initial therapy? Patients with more severe degrees of incontinence, those who want to be dry as soon as possible, and perhaps patients who have undergone postoperative radiation therapy, although neither treatment is optimal for the latter patients. Patients with poor manual dexterity would be better served with collagen injections. In summary, no single incontinence procedure is appropriate for all patients. The union of proper patient selection and surgical expertise in the various techniques for treating PPI will naturally lead to some patients undergoing collagen injection therapy and others receiving an AUS as their initial therapy. Patient satisfaction, however, depends on an understanding of all the treatment options with their inherent risks, benefits, and long-term limitations. If collagen is selected, patients must understand that multiple injections at longer than 4-week intervals will be required, with periodic reinjections to maintain dryness. Of the current surgical options available to treat PPI, transurethral collagen injection is the simplest to perform, is the least morbid, and remains very cost-effective when performed in the clinic in properly selected patients.
UROLOGY 55 (1), 2000
REFERENCES 1. Cespedes RD, O’Connell HE, and McGuire EJ: Collagen injection therapy for the treatment of male urinary incontinence (abstract). J Urol 155: 458A, 1996. 2. Smith DN, Appell RA, Rackley RR, et al: Collagen injection therapy for post-prostatectomy incontinence. J Urol 160: 364 –367, 1998. 3. Bevan-Thomas R, Wesley OL, Cespedes RD, et al: Long term follow-up of periurethral collagen injections for male intrinsic deficiency (abstract). J Urol 161(suppl): 257A, 1999. 4. Sanchez-Ortiz RF, Broderick GA, Chaikin DC, et al: Collagen injection therapy for post radical retropubic prostatectomy incontinence: the role of Valsalva leak point pressure. J Urol 158: 2132–2136, 1997. 5. Wainstein MA, and Klutke CG: Antegrade techniques of collagen injection for post-prostatectomy stress urinary incontinence: the Washington University experience. World J Urol 15: 310 –315, 1997. 6. Appell RA, Vasavada SP, Rackley RR, et al: Percutaneous antegrade collagen injection therapy for urinary incontinence following radical prostatectomy. Urology 48: 769 –772, 1996. 7. Griebling TL, Kreder KJ Jr, and Williams RD: Transurethral collagen injection for treatment of postprostatectomy urinary incontinence in men. Urology 49: 907–912, 1997. 8. Stothers L, Chopra A, and Raz S: A cost effectiveness and utility analysis of the artificial urinary sphincter and collagen injection in the treatment of postprostatectomy incontinence (abstract). J Urol 155: 278A, 1995. 9. Cespedes RD, Kaufmann AM, and McGuire EJ: A cost effectiveness comparison of collagen injection therapy and the artificial urinary sphincter for the treatment of postprostatectomy incontinence. Presented at the South Central Section of the American Urological Association, Vail, Colorado, September 6 –10, 1996. 10. Gundian JC, Barrett DM, and Parulkar BG: Mayo Clinic experience with the use of the AMS 800 artificial urinary sphincter for urinary incontinence following radical prostatectomy. J Urol 142: 1459 –1461, 1989. 11. Martins FE, and Boyd SD: Artificial urinary sphincter in patients following major pelvic surgery and/or radiation. J Urol 153: 1188 –1193, 1995. 12. Brown JA, Elliott DS, and Barrett DM: Postprostatectomy urinary incontinence: a comparison of the cost of conservative versus surgical management. Urology 51: 715–720, 1998. 13. Litwiller SE, Kim KB, Fone PD, et al: Post-prostatectomy incontinence and the artificial urinary sphincter: a long term study of patient satisfaction and criteria for success. J Urol 156: 1975–1980, 1996. 14. Elliott DS, and Barrett DM: Mayo Clinic long-term analysis of the functional durability of the AMS 800 artificial urinary sphincter: a review of 323 cases. J Urol 159: 1206 –1208, 1998.
7
COLLAGEN INJECTION OR ARTIFICIAL SPHINCTER FOR POSTPROSTATECTOMY INCONTINENCE: COLLAGEN R. DUANE CESPEDES
T
he nature of this debate would suggest that collagen injection therapy and the artificial urinary sphincter (AUS) are competitive therapies and that only one procedure should be used at the exclusion of the other. In actuality, these therapies are complementary, each one being useful for selected groups of patients. When performing collagen injections, as with any procedure, proper patient selection and the establishment of optimal methods of treatment delivery are crucial for therapeutic success and patient satisfaction. At the time of Food and Drug Administration approval in December 1993, there was little information regarding this, and unfortunately, many patients subsequently “failed” collagen injection therapy because of this lack of data. Thereafter, many physicians were reluctant to treat patients with collagen, and some have since concluded that collagen injection therapy simply does not work for postprostatectomy incontinence (PPI). Recent data would suggest that collagen injection therapy does indeed work well in properly selected patients when the injections are performed according to the methods developed and perfected during the past few years. The data pertaining to proper patient selection are perhaps the most important gathered thus far. A study from 1996 noted that in postprostatectomy patients who used fewer than six pads per day, 72% were dry or significantly improved at 7 months after injection; only 29% of patients using more than six pads per day were dry.1 Additionally, patients who used fewer than three pads per day were dry or significantly improved in more than 80% of cases. Poor prognostic factors included postopera-
The opinions contained herein are those of the authors and are not to be construed as reflecting the views of the Air Force or the Department of Defense. From the Department of Urology, Wilford Hall Medical Center, Lackland Air Force Base, Texas Reprint requests: R. Duane Cespedes, M.D., Female Urology and Urodynamics, Department of Urology (MMKU), Wilford Hall Medical Center, Lackland Air Force Base, TX 78236 Submitted: July 2, 1999, accepted (with revisions): August 31, 1999 PUBLISHED BY ELSEVIER SCIENCE INC.
tive radiation therapy, adjuvant cryotherapy, and vigorous bladder neck incisions. In the study, the patients rendered dry required a mean of 4.2 injections and 29 mL of collagen. Smith and colleagues2 reported a 38% overall cure rate in 54 patients with a mean follow-up of 29 months; however, in the group of patients who used three pads a day or less, they found a 50% cure rate. Patients rendered dry required a mean of four injections and 20.0 mL of collagen. Bevan-Thomas and colleagues3 recently reported their long-term data of 257 patients after prostatectomy, with a mean follow-up of 28 months. They found that 20% of patients were dry and an additional 39% were significantly improved, for an overall 59% dry or significantly improved rate. Patients who had milder degrees of incontinence and had not received adjuvant radiation or bladder neck incision fared better. A mean of 4.4 injections and 36 mL of collagen were used to obtain dryness in these patients. In a recent study4 focusing on the preoperative evaluation, the abdominal leak point pressure (ALPP) was found to be predictive of postoperative success when using collagen injection therapy. Sanchez-Ortiz and colleagues4 found that patients with a preoperative ALPP greater than 60 cm H2O were cured in 70% of cases, and those with an ALPP less than 60 cm H2O had a 19% cure rate. The data emanating from these studies confirm that the best results can be obtained by selecting patients with milder degrees of incontinence and a preoperative ALPP greater than 60 cm H2O. Important procedural techniques have also been learned from these studies. It is clear that the technique of injecting smaller quantities (2.5 to 7.5 mL) of collagen at longer intervals (greater than 4 weeks) and giving a minimum of four injections yields better cure rates. What this means is that published studies in which an average of two or three injections were given are of little clinical value. Transient but significant improvement after the first or second injection is not a cause for disappointment, as these patients will usually have a good result if additional injections are performed. UROLOGY 55: 5–7, 2000 PII S0090-4295(99)00418-5 5
In similar fashion, if a durable and significant improvement is noted after three or four injections, it is likely that further injections will yield further improvement in continence. Calling the procedure a failure when significant improvement is not observed after one or two injections does not constitute an adequate trial. A common clinical scenario involves the patient with PPI who initially desires collagen injection therapy, but after one or two injections have been performed in the operating room with little improvement and significant expense, considers the procedure a failure and an AUS is recommended. Consequently, if the patient is unwilling to undergo a minimum of four injections and wait the time necessary to perform them, it is probably better to undergo some other form of therapy, as injecting collagen once or twice and subsequently changing or stopping therapy is wasteful of time and money. Although most investigators have performed collagen injections using a retrograde, transurethral route, some investigators have reported good results using a transvesical antegrade approach. Wainstein and Klutke5 reported an encouraging 25% dry and 45% significantly improved rate at a mean 8.5 months of follow-up in their postprostatectomy population. Appell and colleagues6 also observed an encouraging 75% dry rate in their patients after 6 months of follow-up. At the 12-month follow-up evaluation, the “cure rate” had decreased to 37.5%; however, continence presumably would have been restored after an additional injection. Other aspects of collagen injection therapy that appear to be important for therapeutic success but are more difficult to quantify include the degree of tissue scarring, the length of the suprasphincteric urethra, surgeon experience, and the use of specialized injection equipment. Although specialized equipment is not required for injecting collagen, the ease of administration, collagen wastage, and overall results appear to be improved when it is used. Another important question answered by these early studies was, how often will reinjection be necessary after continence is achieved? Since not all patients rendered dry have required reinjection, the range is not known; however, Smith and colleagues2 found that of their patients who became continent, 60.9% were dry at 1 year and 42.8% were dry at 2 years. Another study with 36 dry patients noted that at 6 months after injection, only 1 patient required one additional injection to regain continence.1 Note that the requirement for periodic collagen reinjection can also bias longterm data, since some patients initially rendered dry with collagen who subsequently develop recurrent incontinence may be considered a “failure” 6
when in fact the patient simply needs another collagen injection. The cost-effectiveness of collagen injection therapy has also become a controversial issue. Some reports have concluded that collagen injection therapy, when compared with the AUS, is not cost effective.7,8 In these studies, injections were performed in the operating room using a limited number of injections, with resulting poor cure rates. A cost-effectiveness study comparing two combined AUS series with collagen injections performed in the office using Medicare reimbursement has been performed.9 –11 That study found that collagen injection therapy cost $6021 and the AUS cost $11,933 to achieve comparable levels of continence when a sufficient number of injections were given using the techniques described above. When the long-term (10 years) management costs of treatment, potential reinjections, surgical revisions, and failures in each group were factored into the equation, the total cost in the collagen group was $7884, and the projected total cost in the AUS group was $16,103. A recent report by Brown and colleagues12 presented data that further support the cost-effectiveness of collagen injections when compared with both the AUS and conservative therapy. Overall, collagen appears to be more costeffective than an AUS in the postprostatectomy patient with mild to moderate incontinence when injections are performed in the clinic. Although the AUS is also an excellent choice for the treatment of PPI in properly selected patients, it too has its drawbacks. A careful review of 50 patients who received an AUS for PPI highlights the long-term results of placing an AUS.13 At a mean follow-up of 23 months, the investigators found that only 20% of patients were completely dry, 50% leaked urine on a daily basis, and 24% of patients wore an average of 1.5 pads per day. Additionally, surgical revisions were necessary in 26% of patients. A more recent review of 323 patients who received an AUS with a minimum follow-up of 18 months revealed a similar 27% reoperation rate for mechanical and nonmechanical reasons.14 Despite these results and the need for revisions, most patients were satisfied with the device. The quality of life is undoubtedly improved in most patients after AUS placement because of the dramatic improvement in continence within a very short time; however, collagen does not have that luxury, since it requires multiple injections for a longer period, and the improvements are much more gradual. Finally, in addition to the initial expense of the AUS and the inherent morbidity of an operation, one must consider the significant cost and morbidity of surgical revisions. The decision to proceed with either collagen injection therapy or an AUS must be tempered by an UROLOGY 55 (1), 2000
understanding of the comparative risks and benefits, treatment costs, and long-term complications and requirements of both modalities. Consequently, who is the ideal candidate for collagen injection therapy? The ideal candidate for collagen injection therapy is a patient who uses three pads or fewer per day, has adequate suprasphincteric length for injection, has an ALPP greater than 60 cm H2O, and has not undergone postoperative radiation therapy, cryotherapy, or bladder neck incision. Additionally, the patient must be willing to undergo multiple injections during a prolonged period, with the knowledge that if dryness is achieved, periodic reinjections will be required to maintain it. With the decreasing age of the prostatectomy patient, improvements in surgical techniques, and the inherent desire to avoid surgery, many patients will fulfill these criteria. Which patients are candidates to receive an AUS as the initial therapy? Patients with more severe degrees of incontinence, those who want to be dry as soon as possible, and perhaps patients who have undergone postoperative radiation therapy, although neither treatment is optimal for the latter patients. Patients with poor manual dexterity would be better served with collagen injections. In summary, no single incontinence procedure is appropriate for all patients. The union of proper patient selection and surgical expertise in the various techniques for treating PPI will naturally lead to some patients undergoing collagen injection therapy and others receiving an AUS as their initial therapy. Patient satisfaction, however, depends on an understanding of all the treatment options with their inherent risks, benefits, and long-term limitations. If collagen is selected, patients must understand that multiple injections at longer than 4-week intervals will be required, with periodic reinjections to maintain dryness. Of the current surgical options available to treat PPI, transurethral collagen injection is the simplest to perform, is the least morbid, and remains very cost-effective when performed in the clinic in properly selected patients.
UROLOGY 55 (1), 2000
REFERENCES 1. Cespedes RD, O’Connell HE, and McGuire EJ: Collagen injection therapy for the treatment of male urinary incontinence (abstract). J Urol 155: 458A, 1996. 2. Smith DN, Appell RA, Rackley RR, et al: Collagen injection therapy for post-prostatectomy incontinence. J Urol 160: 364 –367, 1998. 3. Bevan-Thomas R, Wesley OL, Cespedes RD, et al: Long term follow-up of periurethral collagen injections for male intrinsic deficiency (abstract). J Urol 161(suppl): 257A, 1999. 4. Sanchez-Ortiz RF, Broderick GA, Chaikin DC, et al: Collagen injection therapy for post radical retropubic prostatectomy incontinence: the role of Valsalva leak point pressure. J Urol 158: 2132–2136, 1997. 5. Wainstein MA, and Klutke CG: Antegrade techniques of collagen injection for post-prostatectomy stress urinary incontinence: the Washington University experience. World J Urol 15: 310 –315, 1997. 6. Appell RA, Vasavada SP, Rackley RR, et al: Percutaneous antegrade collagen injection therapy for urinary incontinence following radical prostatectomy. Urology 48: 769 –772, 1996. 7. Griebling TL, Kreder KJ Jr, and Williams RD: Transurethral collagen injection for treatment of postprostatectomy urinary incontinence in men. Urology 49: 907–912, 1997. 8. Stothers L, Chopra A, and Raz S: A cost effectiveness and utility analysis of the artificial urinary sphincter and collagen injection in the treatment of postprostatectomy incontinence (abstract). J Urol 155: 278A, 1995. 9. Cespedes RD, Kaufmann AM, and McGuire EJ: A cost effectiveness comparison of collagen injection therapy and the artificial urinary sphincter for the treatment of postprostatectomy incontinence. Presented at the South Central Section of the American Urological Association, Vail, Colorado, September 6 –10, 1996. 10. Gundian JC, Barrett DM, and Parulkar BG: Mayo Clinic experience with the use of the AMS 800 artificial urinary sphincter for urinary incontinence following radical prostatectomy. J Urol 142: 1459 –1461, 1989. 11. Martins FE, and Boyd SD: Artificial urinary sphincter in patients following major pelvic surgery and/or radiation. J Urol 153: 1188 –1193, 1995. 12. Brown JA, Elliott DS, and Barrett DM: Postprostatectomy urinary incontinence: a comparison of the cost of conservative versus surgical management. Urology 51: 715–720, 1998. 13. Litwiller SE, Kim KB, Fone PD, et al: Post-prostatectomy incontinence and the artificial urinary sphincter: a long term study of patient satisfaction and criteria for success. J Urol 156: 1975–1980, 1996. 14. Elliott DS, and Barrett DM: Mayo Clinic long-term analysis of the functional durability of the AMS 800 artificial urinary sphincter: a review of 323 cases. J Urol 159: 1206 –1208, 1998.
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