Prostatic Diseases and Male Voiding Dysfunction Outcomes After Photoselective Vaporization of the Prostate and Transurethral Resection of the Prostate in Patients Who Develop Prostatic Obstruction After Radiation Therapy Benjamin Abelson, Chandana A. Reddy, Jay P. Ciezki, Kenneth Angermeier, James Ulchaker, Eric A. Klein, and Hadley M. Wood OBJECTIVE
METHODS
RESULTS
CONCLUSION
To compare the need for repeat treatment or urinary diversion in patients undergoing transurethral resection of the prostate (TURP) compared with photoselective vaporization of the prostate (PVP) after brachytherapy or external beam radiation therapy (EBRT). The prostate cancer database of Cleveland Clinic includes 3600 patients who have undergone prostate brachytherapy and 2500 patients who have undergone EBRT. We cross-referenced these patients with the electronic medical record to identify patients who required PVP or TURP after radiation. The primary outcome was the need for any further intervention after PVP or TURP, including bladder neck incision, repeat TURP, or permanent supravesicular diversion. Sixty of the 3600 patients (1.7%) required prostate reduction surgery after brachytherapy. Of these 60 patients, 19 of 40 (47.5%) who underwent TURP required further intervention, and 10 of 20 patients (50%) who underwent PVP required subsequent intervention. Twenty-eight of the 2500 patients (1.1%) required prostate reduction surgery after EBRT. Of these 28 patients, 5 of 18 patients (27.8%) who underwent TURP required further intervention, and 5 of 10 patients (50%) who underwent PVP required subsequent intervention. Following either type of radiation there was not a significant difference in the need for further treatment based on the type of surgery (P >.999 for brachytherapy; P ¼ .412 for EBRT). The median time between radiation and prostate reduction surgery is 20.2 months (range, 14.6-27.6) after brachytherapy and 53.3 months (range, 27.5-53.3) after EBRT (P ¼ .0005). This study suggests that PVP and TURP are comparable in treating prostatic obstruction after brachytherapy or EBRT. However, obstruction after brachytherapy occurs earlier compared with after EBRT. UROLOGY 83: 422e427, 2014. 2014 Elsevier Inc.
P
atients with prostate cancer who undergo brachytherapy or external beam radiation therapy (EBRT) are at risk of developing chronic urinary retention that requires surgical intervention.1,2 Previous studies report that up to 10% of patients require an invasive procedure for urinary complications after brachytherapy, and 2.3%-6.6% of patients require transurethral resection
Financial Disclosure: Kenneth Angermeier is a meeting participant and lecturer for American Medical Systems and Endo. James Ulchaker is a meeting participant, lecturer, and researcher for American Medical Systems. The remaining authors declare that they have no relevant financial interests. From the Cleveland Clinic Lerner College of Medicine, Cleveland, OH; the Radiation Oncology, Cleveland Clinic, Cleveland, OH; and the Cleveland Clinic Glickman Urological and Kidney Institute, Cleveland, OH Reprint requests: Hadley M. Wood, M.D., Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue, Q10-1, Cleveland, OH 44195. E-mail: [email protected] Submitted: August 22, 2013, accepted (with revisions): September 23, 2013
422
ª 2014 Elsevier Inc. All Rights Reserved
of the prostate (TURP) for chronic urinary retention after brachytherapy.3-6 Rates of chronic urinary retention have been reported to be slightly lower after EBRT, occurring in up to 3% of patients.7 Surgical management of obstruction after radiation presents a unique challenge, given the reduced healing capacity of irradiated tissue. Standard TURP has historically been the treatment of choice for bladder outlet obstruction after radiation therapy, although reports indicate that up to 70% of these patients develop chronic incontinence after surgery.5,8 Furthermore, over 10% of these patients require more than 1 procedure, and TURP performed within 2 years of brachytherapy leads to an even higher rate of subsequent complications.1,5 Photoselective vaporization of the prostate (PVP) has become increasingly popular in the past decade for treating benign prostatic hyperplasia and provides an 0090-4295/14/$36.00 http://dx.doi.org/10.1016/j.urology.2013.09.047
alternative method of intervention for patients who develop obstruction after radiation therapy.9 However, anecdotal evidence has supported eliminating PVP as an option, given observations of calcific necrosis contributing to intractable obstruction after PVP. This study aims to compare the need for repeat treatment or urinary diversion in patients undergoing TURP compared with patients undergoing PVP after radiation therapy.
MATERIALS AND METHODS Patient Identification The institutional review boardeapproved prostate cancer database of Cleveland Clinic includes 3600 patients who have undergone prostate brachytherapy since 1996 and 2500 patients who have undergone EBRT since 1986. The prostate cancer database is a prospectively maintained database containing clinical, treatment, and follow-up information for all patients treated with radiation therapy from 1986 to present. We crossreferenced these patients with our electronic medical record (EMR) to identify patients who required prostate reduction surgery after brachytherapy or EBRT. After identifying the patients who required surgical procedures, we reviewed operative notes to confirm the type of intervention that was completed, allowing us to dichotomize the patients into 2 groups: those who received traditional TURP (monopolar or bipolar), and those who received a greenlight laser ablation procedure (PVP). The choice of therapy was at the discretion of the treating physician. Cystoscopic findings at follow-up visits and complications requiring further intervention after TURP or PVP were recorded. The primary outcome measure was the need for “any further intervention,” which included bladder neck incision, TURP, or urinary diversion (suprapubic tube or permanent supravesicular diversion) after TURP or PVP. Clinical and demographic characteristics were obtained from the prospective database and the EMR. The EMR and available outside records were reviewed to identify the number and type of further interventions. All procedure notes, office notes, and operative notes were reviewed to optimize the identification of required procedures.
EMR search revealed 60 patients (1.7%) who subsequently required surgical intervention for urinary obstruction, including 40 patients who underwent TURP and 20 patients who underwent PVP (Fig. 1). Baseline characteristics of patients who underwent PVP or TURP did not differ significantly (Table 1). Patients underwent TURP at a median of 20.9 months after brachytherapy (range, 12.6-33.9) and PVP at a median of 20.7 months after brachytherapy (range, 18.4-26.1). The time between brachytherapy and prostate reduction surgery did not correlate with outcome (P ¼ .8991). Mean follow-up was 5.4 years for the TURP patients and 6.7 years for the PVP patients. Of the 40 TURP patients, 19 (47.5%) required subsequent intervention, including 9 patients (22.5%) who required at least 2 further procedures. Indications for TURP included retention or obstructive symptoms (36 patients), hematuria (2 patients), and infection/abscess (2 patients). Of the PVP-treated patients, 10 of 20 (50%) required subsequent instrumentation, including 4 (20%) who underwent at least 2 procedures. Indications for PVP included retention or obstructive symptoms (19 patients) and recurrent urinary tract infections (1 patient). Three patients (3 of 40, 7.5%) who underwent TURP required 4 or more procedures after their initial surgery, including 1 patient who underwent permanent diversion with an ileal conduit. One patient (1 of 20, 5%) who underwent PVP required 4 or more procedures, eventually requiring 3 bladder neck incisions, 1 TURP, and an artificial urinary sphincter implantation. There was no statistically significant difference in the need for repeat procedures based on whether the patient initially underwent TURP or PVP (P >.9999). The risk of chronic incontinence after prostate reduction surgery was not significantly different between the patients who underwent TURP and those who underwent PVP (P ¼ .7833). Sixteen of 40 patients who underwent TURP (40%) developed chronic incontinence (more than 1 year after TURP), and 7 of 20 patients who underwent PVP (35%) developed chronic incontinence.
Data Analysis Baseline characteristics, including body mass index, prostate volume, age at radiation, and time between radiation and the initial procedure were compared between patients who underwent TURP and those who underwent PVP. The MannWhitney U test was used to compare continuous data, and Fisher’s exact test for comparing categorical data between the 2 groups. The proportion of patients requiring further interventions in the PVP and TURP groups was compared using Fischer’s exact tests. Logistic regression was used to examine if time between radiation and the initial procedure correlated with the need for additional procedures. Statistical significance was considered as P .9990 28.2 (26.3, 30.1) 26.6 (26.0, 28.2) .0761 e e e
.5777
55.0 (25, 80)
.3118
8.7 (6.0, 10.9)
45.0 (22, 53)
8.2 (6.3, 10.0)
.0685
.7553
BMI, body mass index; CaP, prostate cancer; EBRT, external beam radiation therapy; PVP, photoselective vaporization of the prostate; TURP, transurethral resection of the prostate.
procedures. Indications for TURP included retention or obstructive symptoms (16 patients), recurrent urinary tract infections (1 patient), and infection/abscess (1 patient). Of the PVP-treated patients, 5 of 10 patients (50%) required subsequent instrumentation, none of whom required more than 1 revision treatment. Indications for PVP included retention or obstructive symptoms (9 patients) and hematuria (1 patient). There was no statistically significant difference in the need for repeat procedures based on whether the patient initially underwent TURP or PVP (P ¼ .412). The risk of chronic incontinence after prostate reduction surgery was not significantly different between the patients who underwent TURP and those who underwent PVP (P ¼ .4170). Seven of 18 patients who underwent TURP (39%) developed chronic incontinence 424
(more than 1 year after TURP), and 2 of 10 patients who underwent PVP (20%) developed chronic incontinence. Combined Analysis: Chronic Urinary Obstruction After EBRT or Brachytherapy A Fisher’s exact test compared the number of patients who required TURP or PVP in the EBRT and brachytherapy groups. Twenty-eight of 2500 (1.1%) EBRT patients and 60 of 3600 (1.6%) brachytherapy patients underwent TURP or PVP after radiation therapy, indicating there is no significant difference in the risk of requiring surgical intervention for prostatic obstruction (P ¼ .81). Given the comparable incidence of chronic obstruction after brachytherapy and EBRT, the 2 groups were combined for a pooled analysis of the efficacy of PVP vs UROLOGY 83 (2), 2014
Figure 2. External beam radiation therapy patient flowchart.
TURP. Of the 58 patients who underwent TURP after brachytherapy or EBRT, 15 (26%) required additional intervention, and of the 30 patients who underwent PVP, 15 (50%) required additional intervention. In the pooled analysis, there was still no evidence to support PVP or TURP as more effective in treating bladder outlet obstruction after radiation therapy for prostate cancer (P ¼ .5009). However, there was a difference between the EBRT and brachytherapy patients in terms of the time between radiation and the need for surgical intervention for chronic urinary retention (P ¼ .0005). Figure 3 demonstrates that the median time between brachytherapy and PVP or TURP is 20.2 months (range, 14.6-27.6), and the median time between EBRT and PVP or TURP is 53.3 months (range, 27.5-80.6).
COMMENT We compared outcomes of PVP with TURP for patients who develop bladder outlet obstruction after brachytherapy or external beam radiation. This study suggests that both treatments are comparable in successfully treating the obstruction and preventing the need for repeat procedures. Regardless of the procedure, approximately half of patients who undergo PVP or TURP after radiation for prostate cancer will require further surgical intervention such as bladder neck incision, repeat TURP, or rarely, urinary diversion. We had observed a number of patients referred for treatment with prostatic calcific necrosis who underwent PVP after brachytherapy and designed this study to investigate whether TURP is a more successful treatment option. The conclusions—that PVP does not appear to increase the risk of recalcitrant bladder neck obstruction UROLOGY 83 (2), 2014
compared with TURP—were surprising, given that PVP is most effective in vascular tissue. It is important to note that we do not perform dual modality radiation treatment for prostate cancer at Cleveland Clinic, and therefore these patients are not represented in our study. Our conclusions serve to challenge the assumption that patients who develop chronic obstruction after brachytherapy or EBRT should be treated with TURP instead of PVP. However, we do not argue that PVP might provide a reasonable alternative for all patients and all providers, given that patient selection and surgeon preference likely impacted our results and should continue to drive treatment decisions. Our registry includes several surgeons, some of whom routinely use PVP, and others who more commonly use TURP, which might impact the choice of surgical intervention and the outcome. Given the comparable outcomes of TURP and PVP for patients who develop chronic urinary retention after radiation therapy, the question important to clinicians becomes identifying which patients might develop recalcitrant obstruction after initial TURP or PVP. Previous studies have identified multiple negative prognostic factors for urinary obstruction, with prebrachytherapy American Urological Association Symptom Index scores consistently shown to be the most predictive of obstruction after radiation.10,11 Our group previously reported that increased prostate length was predictive of the need for intermittent self-catheterization after brachytherapy.12 The study population was selected on the basis of the occurrence of obstruction; therefore, we cannot make conclusions regarding preradiation therapy characteristics that might predict complications. However, evaluation of our patients can help identify treatment and patient variables that can prevent recurrence of obstruction after 425
Figure 3. Time to photoselective vaporization of the prostate or transurethral resection of the prostate after radiation therapy. (Each observation represents 1 patient). (Color version available online.)
TURP/PVP. It has been previously recommended that TURP after brachytherapy be delayed at least 12 months because of the poor healing of highly irradiated tissue.4,13 Although most patients in our series were treated at least 12 months after brachytherapy or EBRT, there were no differences in success rates with prostate reduction surgery with longer duration from completion of radiation treatment. In fact, several patients who did not undergo TURP or PVP until more than 4 years after radiation still suffered from recalcitrant obstruction. Such late obstruction could be explained by permanent changes in prostatic urethral tissue after almost complete elimination of active radiation or characteristics unrelated to the patient’s history of radiation. There was a significant difference in the time delay until surgery when comparing the EBRT patients with the brachytherapy patients (Fig. 3). This finding could be explained by differences in follow-up time, which were longer in the EBRT group than in the brachytherapy group. However, in the first 5 years of follow-up, 90% of the patients who would eventually require a procedure after brachytherapy had already undergone TURP or PVP, whereas only 40% of the EBRT patients had undergone their procedures, indicating that obstruction occurs earlier after brachytherapy. The finding that chronic obstruction occurs later after EBRT is somewhat surprising, particularly because patients with larger prostates and higher pretreatment American Urological Association Symptom Score would be more likely to have been steered toward an alternative treatment (surgery, ablative therapy, and active surveillance) in the brachytherapy era. This suggests that the local effect of brachytherapy exacerbates obstructive 426
symptoms by causing more prostate edema, bladder neck edema, or scarring in the 1-2 year period immediately after treatment. Alternatively, one could suspect that the longer duration of time between EBRT and development of symptoms requiring treatment might be because of a long-term effect on the bladder itself, less so than on the bladder neck or prostate. We do not have urodynamic data to support this theory but suggest it as an area of further investigation. Several potential limitations might impact the outcomes of this study, although we do not believe that they would significantly alter the primary conclusions. Given the retrospective nature of the study, we were unable to control for variables such as comorbidities or surgeon experience that might have impacted success of the initial TURP or PVP. Furthermore, the common assumption held by many surgeons that PVP might be less ideal for radiated patients might have affected which patients received this therapy, introducing selection bias into the results. Another shortcoming of this study is its single institution design, and we recognize that some patients who received radiation therapy at Cleveland Clinic and subsequently required TURP or PVP might have sought care elsewhere. However, our institution accounts for 57% of local urologic care; therefore, we assume that we did not lose significant numbers of patients to follow-up.
CONCLUSION Patients who develop prostatic obstruction after brachytherapy or EBRT often require multiple surgical procedures and in some cases require permanent urinary diversion. This study compared traditional TURP with UROLOGY 83 (2), 2014
PVP, with the aim of identifying a superior strategy for managing prostatic obstruction after radiation therapy for prostate cancer. The evidence indicates that up to 50% of patients who undergo TURP or PVP after radiation will require further surgical intervention for obstruction— regardless of which procedure is chosen. References 1. Kao J, Cesaretti JA, Stone NN, et al. Update on prostate brachytherapy: long-term outcomes and treatment-related morbidity. Curr Urol Rep. 2011;12:237-242. 2. Anandadas CN, Clarke NW, Davidson SE, et al. Early prostate cancerewhich treatment do men prefer and why? BJU Int. 2011; 107:1762-1768. 3. Chen AB, D’Amico AV, Neville BA, et al. Patient and treatment factors associated with complications after prostate brachytherapy. J Clin Oncol. 2006;24:5298-5304. 4. Cameron A. Management of acute and chronic urinary complications of radiation therapy for prostate cancer. AUA Update Ser. 2008;27:305-319. 5. Kollmeier MA, Stock RG, Cesaretti J, et al. Urinary morbidity and incontinence following transurethral resection of the prostate after brachytherapy. J Urol. 2005;173:808-812. 6. Merrick GS, Butler WM, Wallner KE, et al. Effect of transurethral resection on urinary quality of life after permanent prostate brachytherapy. Int J Radiat Oncol Biol Phys. 2004;58:81-88. 7. Elliott SP, McAninch JW, Chi T, et al. Management of severe urethral complications of prostate cancer therapy. J Urol. 2006;176: 2508-2513. 8. Hu K, Wallner K. Urinary incontinence in patients who have a TURP/TUIP following prostate brachytherapy. Int J Radiat Oncol Biol Phys. 1998;40:783-786. 9. Teng J, Zhang D, Li Y, et al. Photoselective vaporization with the green light laser vs transurethral resection of the prostate for treating benign prostate hyperplasia: a systematic review and meta-analysis. BJU Int. 2013;111:312-323. 10. Terk MD, Stock RG, Stone NN. Identification of patients at increased risk for prolonged urinary retention following radioactive seed implantation of the prostate. J Urol. 1998;160:1379-1382. 11. Mabjeesh NJ, Chen J, Stenger A, et al. Preimplant predictive factors of urinary retention after iodine 125 prostate brachytherapy. Urology. 2007;70:548-553. 12. Elshaikh MA, Angermeier K, Ulchaker JC, et al. Effect of anatomic, procedural, and dosimetric variables on urinary retention after permanent iodine-125 prostate brachytherapy. Urology. 2003;61:152-155. 13. Merrick GS, Wallner KE, Butler WM. Minimizing prostate brachytherapy-related morbidity. Urology. 2003;62:786-792.
EDITORIAL COMMENT Patients who have radiation for prostate cancer and go on to have a transurethral resection of the prostate or a photoselective vaporization of the prostate for obstructive symptoms have poor results. This highlights the need for careful patient selection. The numbers affected in this study are small but the results are significant; about half of the patients need further surgery for obstruction.1
UROLOGY 83 (2), 2014
It is challenging in a database to capture all surgical complications when patients have the option of following up elsewhere. This suggests that the true obstruction rate is higher than that presented. Patients might be motivated to seek cancer care at great distance but might be more content to have their obstructive symptoms dealt with closer to home. This might skew the data published by academic centers. As the authors acknowledge, there is likely some selection bias, but as the results are similar for both modalities, it suggests that a surgeon’s experience with the technique is perhaps more important than the technique itself. In this study, surgeons had their own preferences, and this might have improved their outcomes. In this regard, these results can be considered the best-case scenario. As both sets of patients do relatively poorly, this suggests that further innovation is needed to develop newer surgical techniques to deal with this challenging subset of patients. 1
Outcomes after photoselective vaporization of the prostate and transurethral resection of the prostate in patients who develop prostatic obstruction following radiation therapy. Darius J. Unwala, M.B.Ch.B. (Hons.), M.R.C.S. (Eng.), F.R.C.S.C. (Urol.), F.A.C.S., Department of Urology, Princess Margaret Hospital, Nassau, Bahamas http://dx.doi.org/10.1016/j.urology.2013.09.048 UROLOGY 83: 427, 2014. 2014 Elsevier Inc.
REPLY This project was conceived after we observed several patients who came to our clinic with severe calcific necrosis of the prostate after brachytherapy and laser prostate reduction surgery. Most of the patients we have anecdotally observed having recalcitrant obstruction or need for permanent urinary diversion did not receive primary radiation or prostate reduction surgery at our institution. Yet, we were unable to present our findings without identifying a population from which we could determine the “denominator” of patients who were affected. This led us to design the present study using our institutional radiation therapy database, which admittedly might demonstrate the faults of database studies as has been discussed. Moreover, our cohorts are highly selected, and we do not use dual radiation treatment at our institution and therefore suspect that prostatic obstruction might be more common in the population as a whole. The questions raised in the article and in this discussion illustrate the need for better outcomes reporting across disciplines and modalities so that more accurate comparative data might emerge. Hadley M. Wood, M.D., F.A.C.S., Cleveland Clinic Glickman Urological and Kidney Institute, Cleveland, OH http://dx.doi.org/10.1016/j.urology.2013.09.049 UROLOGY 83: 427, 2014. 2014 Elsevier Inc.
427
METHODS
RESULTS
CONCLUSION
To compare the need for repeat treatment or urinary diversion in patients undergoing transurethral resection of the prostate (TURP) compared with photoselective vaporization of the prostate (PVP) after brachytherapy or external beam radiation therapy (EBRT). The prostate cancer database of Cleveland Clinic includes 3600 patients who have undergone prostate brachytherapy and 2500 patients who have undergone EBRT. We cross-referenced these patients with the electronic medical record to identify patients who required PVP or TURP after radiation. The primary outcome was the need for any further intervention after PVP or TURP, including bladder neck incision, repeat TURP, or permanent supravesicular diversion. Sixty of the 3600 patients (1.7%) required prostate reduction surgery after brachytherapy. Of these 60 patients, 19 of 40 (47.5%) who underwent TURP required further intervention, and 10 of 20 patients (50%) who underwent PVP required subsequent intervention. Twenty-eight of the 2500 patients (1.1%) required prostate reduction surgery after EBRT. Of these 28 patients, 5 of 18 patients (27.8%) who underwent TURP required further intervention, and 5 of 10 patients (50%) who underwent PVP required subsequent intervention. Following either type of radiation there was not a significant difference in the need for further treatment based on the type of surgery (P >.999 for brachytherapy; P ¼ .412 for EBRT). The median time between radiation and prostate reduction surgery is 20.2 months (range, 14.6-27.6) after brachytherapy and 53.3 months (range, 27.5-53.3) after EBRT (P ¼ .0005). This study suggests that PVP and TURP are comparable in treating prostatic obstruction after brachytherapy or EBRT. However, obstruction after brachytherapy occurs earlier compared with after EBRT. UROLOGY 83: 422e427, 2014. 2014 Elsevier Inc.
P
atients with prostate cancer who undergo brachytherapy or external beam radiation therapy (EBRT) are at risk of developing chronic urinary retention that requires surgical intervention.1,2 Previous studies report that up to 10% of patients require an invasive procedure for urinary complications after brachytherapy, and 2.3%-6.6% of patients require transurethral resection
Financial Disclosure: Kenneth Angermeier is a meeting participant and lecturer for American Medical Systems and Endo. James Ulchaker is a meeting participant, lecturer, and researcher for American Medical Systems. The remaining authors declare that they have no relevant financial interests. From the Cleveland Clinic Lerner College of Medicine, Cleveland, OH; the Radiation Oncology, Cleveland Clinic, Cleveland, OH; and the Cleveland Clinic Glickman Urological and Kidney Institute, Cleveland, OH Reprint requests: Hadley M. Wood, M.D., Glickman Urological and Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue, Q10-1, Cleveland, OH 44195. E-mail: [email protected] Submitted: August 22, 2013, accepted (with revisions): September 23, 2013
422
ª 2014 Elsevier Inc. All Rights Reserved
of the prostate (TURP) for chronic urinary retention after brachytherapy.3-6 Rates of chronic urinary retention have been reported to be slightly lower after EBRT, occurring in up to 3% of patients.7 Surgical management of obstruction after radiation presents a unique challenge, given the reduced healing capacity of irradiated tissue. Standard TURP has historically been the treatment of choice for bladder outlet obstruction after radiation therapy, although reports indicate that up to 70% of these patients develop chronic incontinence after surgery.5,8 Furthermore, over 10% of these patients require more than 1 procedure, and TURP performed within 2 years of brachytherapy leads to an even higher rate of subsequent complications.1,5 Photoselective vaporization of the prostate (PVP) has become increasingly popular in the past decade for treating benign prostatic hyperplasia and provides an 0090-4295/14/$36.00 http://dx.doi.org/10.1016/j.urology.2013.09.047
alternative method of intervention for patients who develop obstruction after radiation therapy.9 However, anecdotal evidence has supported eliminating PVP as an option, given observations of calcific necrosis contributing to intractable obstruction after PVP. This study aims to compare the need for repeat treatment or urinary diversion in patients undergoing TURP compared with patients undergoing PVP after radiation therapy.
MATERIALS AND METHODS Patient Identification The institutional review boardeapproved prostate cancer database of Cleveland Clinic includes 3600 patients who have undergone prostate brachytherapy since 1996 and 2500 patients who have undergone EBRT since 1986. The prostate cancer database is a prospectively maintained database containing clinical, treatment, and follow-up information for all patients treated with radiation therapy from 1986 to present. We crossreferenced these patients with our electronic medical record (EMR) to identify patients who required prostate reduction surgery after brachytherapy or EBRT. After identifying the patients who required surgical procedures, we reviewed operative notes to confirm the type of intervention that was completed, allowing us to dichotomize the patients into 2 groups: those who received traditional TURP (monopolar or bipolar), and those who received a greenlight laser ablation procedure (PVP). The choice of therapy was at the discretion of the treating physician. Cystoscopic findings at follow-up visits and complications requiring further intervention after TURP or PVP were recorded. The primary outcome measure was the need for “any further intervention,” which included bladder neck incision, TURP, or urinary diversion (suprapubic tube or permanent supravesicular diversion) after TURP or PVP. Clinical and demographic characteristics were obtained from the prospective database and the EMR. The EMR and available outside records were reviewed to identify the number and type of further interventions. All procedure notes, office notes, and operative notes were reviewed to optimize the identification of required procedures.
EMR search revealed 60 patients (1.7%) who subsequently required surgical intervention for urinary obstruction, including 40 patients who underwent TURP and 20 patients who underwent PVP (Fig. 1). Baseline characteristics of patients who underwent PVP or TURP did not differ significantly (Table 1). Patients underwent TURP at a median of 20.9 months after brachytherapy (range, 12.6-33.9) and PVP at a median of 20.7 months after brachytherapy (range, 18.4-26.1). The time between brachytherapy and prostate reduction surgery did not correlate with outcome (P ¼ .8991). Mean follow-up was 5.4 years for the TURP patients and 6.7 years for the PVP patients. Of the 40 TURP patients, 19 (47.5%) required subsequent intervention, including 9 patients (22.5%) who required at least 2 further procedures. Indications for TURP included retention or obstructive symptoms (36 patients), hematuria (2 patients), and infection/abscess (2 patients). Of the PVP-treated patients, 10 of 20 (50%) required subsequent instrumentation, including 4 (20%) who underwent at least 2 procedures. Indications for PVP included retention or obstructive symptoms (19 patients) and recurrent urinary tract infections (1 patient). Three patients (3 of 40, 7.5%) who underwent TURP required 4 or more procedures after their initial surgery, including 1 patient who underwent permanent diversion with an ileal conduit. One patient (1 of 20, 5%) who underwent PVP required 4 or more procedures, eventually requiring 3 bladder neck incisions, 1 TURP, and an artificial urinary sphincter implantation. There was no statistically significant difference in the need for repeat procedures based on whether the patient initially underwent TURP or PVP (P >.9999). The risk of chronic incontinence after prostate reduction surgery was not significantly different between the patients who underwent TURP and those who underwent PVP (P ¼ .7833). Sixteen of 40 patients who underwent TURP (40%) developed chronic incontinence (more than 1 year after TURP), and 7 of 20 patients who underwent PVP (35%) developed chronic incontinence.
Data Analysis Baseline characteristics, including body mass index, prostate volume, age at radiation, and time between radiation and the initial procedure were compared between patients who underwent TURP and those who underwent PVP. The MannWhitney U test was used to compare continuous data, and Fisher’s exact test for comparing categorical data between the 2 groups. The proportion of patients requiring further interventions in the PVP and TURP groups was compared using Fischer’s exact tests. Logistic regression was used to examine if time between radiation and the initial procedure correlated with the need for additional procedures. Statistical significance was considered as P .9990 28.2 (26.3, 30.1) 26.6 (26.0, 28.2) .0761 e e e
.5777
55.0 (25, 80)
.3118
8.7 (6.0, 10.9)
45.0 (22, 53)
8.2 (6.3, 10.0)
.0685
.7553
BMI, body mass index; CaP, prostate cancer; EBRT, external beam radiation therapy; PVP, photoselective vaporization of the prostate; TURP, transurethral resection of the prostate.
procedures. Indications for TURP included retention or obstructive symptoms (16 patients), recurrent urinary tract infections (1 patient), and infection/abscess (1 patient). Of the PVP-treated patients, 5 of 10 patients (50%) required subsequent instrumentation, none of whom required more than 1 revision treatment. Indications for PVP included retention or obstructive symptoms (9 patients) and hematuria (1 patient). There was no statistically significant difference in the need for repeat procedures based on whether the patient initially underwent TURP or PVP (P ¼ .412). The risk of chronic incontinence after prostate reduction surgery was not significantly different between the patients who underwent TURP and those who underwent PVP (P ¼ .4170). Seven of 18 patients who underwent TURP (39%) developed chronic incontinence 424
(more than 1 year after TURP), and 2 of 10 patients who underwent PVP (20%) developed chronic incontinence. Combined Analysis: Chronic Urinary Obstruction After EBRT or Brachytherapy A Fisher’s exact test compared the number of patients who required TURP or PVP in the EBRT and brachytherapy groups. Twenty-eight of 2500 (1.1%) EBRT patients and 60 of 3600 (1.6%) brachytherapy patients underwent TURP or PVP after radiation therapy, indicating there is no significant difference in the risk of requiring surgical intervention for prostatic obstruction (P ¼ .81). Given the comparable incidence of chronic obstruction after brachytherapy and EBRT, the 2 groups were combined for a pooled analysis of the efficacy of PVP vs UROLOGY 83 (2), 2014
Figure 2. External beam radiation therapy patient flowchart.
TURP. Of the 58 patients who underwent TURP after brachytherapy or EBRT, 15 (26%) required additional intervention, and of the 30 patients who underwent PVP, 15 (50%) required additional intervention. In the pooled analysis, there was still no evidence to support PVP or TURP as more effective in treating bladder outlet obstruction after radiation therapy for prostate cancer (P ¼ .5009). However, there was a difference between the EBRT and brachytherapy patients in terms of the time between radiation and the need for surgical intervention for chronic urinary retention (P ¼ .0005). Figure 3 demonstrates that the median time between brachytherapy and PVP or TURP is 20.2 months (range, 14.6-27.6), and the median time between EBRT and PVP or TURP is 53.3 months (range, 27.5-80.6).
COMMENT We compared outcomes of PVP with TURP for patients who develop bladder outlet obstruction after brachytherapy or external beam radiation. This study suggests that both treatments are comparable in successfully treating the obstruction and preventing the need for repeat procedures. Regardless of the procedure, approximately half of patients who undergo PVP or TURP after radiation for prostate cancer will require further surgical intervention such as bladder neck incision, repeat TURP, or rarely, urinary diversion. We had observed a number of patients referred for treatment with prostatic calcific necrosis who underwent PVP after brachytherapy and designed this study to investigate whether TURP is a more successful treatment option. The conclusions—that PVP does not appear to increase the risk of recalcitrant bladder neck obstruction UROLOGY 83 (2), 2014
compared with TURP—were surprising, given that PVP is most effective in vascular tissue. It is important to note that we do not perform dual modality radiation treatment for prostate cancer at Cleveland Clinic, and therefore these patients are not represented in our study. Our conclusions serve to challenge the assumption that patients who develop chronic obstruction after brachytherapy or EBRT should be treated with TURP instead of PVP. However, we do not argue that PVP might provide a reasonable alternative for all patients and all providers, given that patient selection and surgeon preference likely impacted our results and should continue to drive treatment decisions. Our registry includes several surgeons, some of whom routinely use PVP, and others who more commonly use TURP, which might impact the choice of surgical intervention and the outcome. Given the comparable outcomes of TURP and PVP for patients who develop chronic urinary retention after radiation therapy, the question important to clinicians becomes identifying which patients might develop recalcitrant obstruction after initial TURP or PVP. Previous studies have identified multiple negative prognostic factors for urinary obstruction, with prebrachytherapy American Urological Association Symptom Index scores consistently shown to be the most predictive of obstruction after radiation.10,11 Our group previously reported that increased prostate length was predictive of the need for intermittent self-catheterization after brachytherapy.12 The study population was selected on the basis of the occurrence of obstruction; therefore, we cannot make conclusions regarding preradiation therapy characteristics that might predict complications. However, evaluation of our patients can help identify treatment and patient variables that can prevent recurrence of obstruction after 425
Figure 3. Time to photoselective vaporization of the prostate or transurethral resection of the prostate after radiation therapy. (Each observation represents 1 patient). (Color version available online.)
TURP/PVP. It has been previously recommended that TURP after brachytherapy be delayed at least 12 months because of the poor healing of highly irradiated tissue.4,13 Although most patients in our series were treated at least 12 months after brachytherapy or EBRT, there were no differences in success rates with prostate reduction surgery with longer duration from completion of radiation treatment. In fact, several patients who did not undergo TURP or PVP until more than 4 years after radiation still suffered from recalcitrant obstruction. Such late obstruction could be explained by permanent changes in prostatic urethral tissue after almost complete elimination of active radiation or characteristics unrelated to the patient’s history of radiation. There was a significant difference in the time delay until surgery when comparing the EBRT patients with the brachytherapy patients (Fig. 3). This finding could be explained by differences in follow-up time, which were longer in the EBRT group than in the brachytherapy group. However, in the first 5 years of follow-up, 90% of the patients who would eventually require a procedure after brachytherapy had already undergone TURP or PVP, whereas only 40% of the EBRT patients had undergone their procedures, indicating that obstruction occurs earlier after brachytherapy. The finding that chronic obstruction occurs later after EBRT is somewhat surprising, particularly because patients with larger prostates and higher pretreatment American Urological Association Symptom Score would be more likely to have been steered toward an alternative treatment (surgery, ablative therapy, and active surveillance) in the brachytherapy era. This suggests that the local effect of brachytherapy exacerbates obstructive 426
symptoms by causing more prostate edema, bladder neck edema, or scarring in the 1-2 year period immediately after treatment. Alternatively, one could suspect that the longer duration of time between EBRT and development of symptoms requiring treatment might be because of a long-term effect on the bladder itself, less so than on the bladder neck or prostate. We do not have urodynamic data to support this theory but suggest it as an area of further investigation. Several potential limitations might impact the outcomes of this study, although we do not believe that they would significantly alter the primary conclusions. Given the retrospective nature of the study, we were unable to control for variables such as comorbidities or surgeon experience that might have impacted success of the initial TURP or PVP. Furthermore, the common assumption held by many surgeons that PVP might be less ideal for radiated patients might have affected which patients received this therapy, introducing selection bias into the results. Another shortcoming of this study is its single institution design, and we recognize that some patients who received radiation therapy at Cleveland Clinic and subsequently required TURP or PVP might have sought care elsewhere. However, our institution accounts for 57% of local urologic care; therefore, we assume that we did not lose significant numbers of patients to follow-up.
CONCLUSION Patients who develop prostatic obstruction after brachytherapy or EBRT often require multiple surgical procedures and in some cases require permanent urinary diversion. This study compared traditional TURP with UROLOGY 83 (2), 2014
PVP, with the aim of identifying a superior strategy for managing prostatic obstruction after radiation therapy for prostate cancer. The evidence indicates that up to 50% of patients who undergo TURP or PVP after radiation will require further surgical intervention for obstruction— regardless of which procedure is chosen. References 1. Kao J, Cesaretti JA, Stone NN, et al. Update on prostate brachytherapy: long-term outcomes and treatment-related morbidity. Curr Urol Rep. 2011;12:237-242. 2. Anandadas CN, Clarke NW, Davidson SE, et al. Early prostate cancerewhich treatment do men prefer and why? BJU Int. 2011; 107:1762-1768. 3. Chen AB, D’Amico AV, Neville BA, et al. Patient and treatment factors associated with complications after prostate brachytherapy. J Clin Oncol. 2006;24:5298-5304. 4. Cameron A. Management of acute and chronic urinary complications of radiation therapy for prostate cancer. AUA Update Ser. 2008;27:305-319. 5. Kollmeier MA, Stock RG, Cesaretti J, et al. Urinary morbidity and incontinence following transurethral resection of the prostate after brachytherapy. J Urol. 2005;173:808-812. 6. Merrick GS, Butler WM, Wallner KE, et al. Effect of transurethral resection on urinary quality of life after permanent prostate brachytherapy. Int J Radiat Oncol Biol Phys. 2004;58:81-88. 7. Elliott SP, McAninch JW, Chi T, et al. Management of severe urethral complications of prostate cancer therapy. J Urol. 2006;176: 2508-2513. 8. Hu K, Wallner K. Urinary incontinence in patients who have a TURP/TUIP following prostate brachytherapy. Int J Radiat Oncol Biol Phys. 1998;40:783-786. 9. Teng J, Zhang D, Li Y, et al. Photoselective vaporization with the green light laser vs transurethral resection of the prostate for treating benign prostate hyperplasia: a systematic review and meta-analysis. BJU Int. 2013;111:312-323. 10. Terk MD, Stock RG, Stone NN. Identification of patients at increased risk for prolonged urinary retention following radioactive seed implantation of the prostate. J Urol. 1998;160:1379-1382. 11. Mabjeesh NJ, Chen J, Stenger A, et al. Preimplant predictive factors of urinary retention after iodine 125 prostate brachytherapy. Urology. 2007;70:548-553. 12. Elshaikh MA, Angermeier K, Ulchaker JC, et al. Effect of anatomic, procedural, and dosimetric variables on urinary retention after permanent iodine-125 prostate brachytherapy. Urology. 2003;61:152-155. 13. Merrick GS, Wallner KE, Butler WM. Minimizing prostate brachytherapy-related morbidity. Urology. 2003;62:786-792.
EDITORIAL COMMENT Patients who have radiation for prostate cancer and go on to have a transurethral resection of the prostate or a photoselective vaporization of the prostate for obstructive symptoms have poor results. This highlights the need for careful patient selection. The numbers affected in this study are small but the results are significant; about half of the patients need further surgery for obstruction.1
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It is challenging in a database to capture all surgical complications when patients have the option of following up elsewhere. This suggests that the true obstruction rate is higher than that presented. Patients might be motivated to seek cancer care at great distance but might be more content to have their obstructive symptoms dealt with closer to home. This might skew the data published by academic centers. As the authors acknowledge, there is likely some selection bias, but as the results are similar for both modalities, it suggests that a surgeon’s experience with the technique is perhaps more important than the technique itself. In this study, surgeons had their own preferences, and this might have improved their outcomes. In this regard, these results can be considered the best-case scenario. As both sets of patients do relatively poorly, this suggests that further innovation is needed to develop newer surgical techniques to deal with this challenging subset of patients. 1
Outcomes after photoselective vaporization of the prostate and transurethral resection of the prostate in patients who develop prostatic obstruction following radiation therapy. Darius J. Unwala, M.B.Ch.B. (Hons.), M.R.C.S. (Eng.), F.R.C.S.C. (Urol.), F.A.C.S., Department of Urology, Princess Margaret Hospital, Nassau, Bahamas http://dx.doi.org/10.1016/j.urology.2013.09.048 UROLOGY 83: 427, 2014. 2014 Elsevier Inc.
REPLY This project was conceived after we observed several patients who came to our clinic with severe calcific necrosis of the prostate after brachytherapy and laser prostate reduction surgery. Most of the patients we have anecdotally observed having recalcitrant obstruction or need for permanent urinary diversion did not receive primary radiation or prostate reduction surgery at our institution. Yet, we were unable to present our findings without identifying a population from which we could determine the “denominator” of patients who were affected. This led us to design the present study using our institutional radiation therapy database, which admittedly might demonstrate the faults of database studies as has been discussed. Moreover, our cohorts are highly selected, and we do not use dual radiation treatment at our institution and therefore suspect that prostatic obstruction might be more common in the population as a whole. The questions raised in the article and in this discussion illustrate the need for better outcomes reporting across disciplines and modalities so that more accurate comparative data might emerge. Hadley M. Wood, M.D., F.A.C.S., Cleveland Clinic Glickman Urological and Kidney Institute, Cleveland, OH http://dx.doi.org/10.1016/j.urology.2013.09.049 UROLOGY 83: 427, 2014. 2014 Elsevier Inc.
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