- Email: [email protected]
Re: Treatment of Adults with Complications from Previous Hypospadias Surgery
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EUROPEAN UROLOGY 63 (2013) 178–182
Re: Quality-of-life Effects of Prostate-specific Antigen Screening Heijnsdijk EA, Wever EM, Auvinen A, et al. N Engl J Med 2012;367:595–605 Expert’s summary: This report used decision modeling to quantify how the benefits of prostate cancer (PCa) screening is counterbalanced by the harms. The authors used data from the European Randomized Study of Screening for Prostate Cancer to predict outcomes under various scenarios. They report that annual screening of men aged 55–69 yr would result in a 28% decrease in PCa deaths, a 35% decrease in palliative treatments, and a total of 73 life-years gained per 1000 men screened (average 8.4 yr per death avoided). However, they discounted the gain by 23% because of offsetting treatment complications, that is, the gain was 56 quality-adjusted life-years (QALYs). To prevent one death, 98 men must be screened and five cancers detected. Screening men aged 55–74 yr resulted in 82 lifeyears gained but the same 56 QALYs.
that most patients will gain from screening because we do not know how many have lower versus higher utilities. If we knew that all have utilities consistent with a gain, then we could recommend universal screening. The US Preventive Services Task Force has recommended against screening in all men [5]. Sox stated that until we know the distribution of utilities for all health states, guidelines should avoid recommending for or against PSA screening but rather should recommend a shared decision process that includes assessing patients’ feelings about what they could go through after screening. In other words, the task force was wrong to downgrade the PSA screening recommendation. Conflicts of interest: The author has received research support and honoraria for speaking from and been an investigator for BeckmanCoulter Inc., has received research support and royalties as co-inventor from and been an investigator and consultant for OHMX Inc., has received research support from and been an investigator for deCODE genetics Inc., and has been an investigator for Nanosphere.
References Expert’s comments: If assumptions used in decision modeling are invalid, they fail to predict reality. Based on European data, the authors assumed that 43% of cancers were overdiagnosed. This is higher than estimates from US models (23–28% [1]) or surgical data (7–20% [2,3]). The authors attempt to quantify the trade-offs by expressing both benefits and harms in life-years. Sox’s accompanying editorial points out that this is like comparing apples and oranges [4]. The years gained by avoiding a PCa death is an objective assessment, but conversion of how a man feels about the number of years of life he would trade to avoid possible future complications he has never experienced (utilities) remains subjective. The cold truth is that it is easier said than done: ‘‘Would you rather live for 6 years with normal continence or for 14 years with a 10% chance of having to wear a pad? How about 7 versus 13?’’ Sox cautioned that the utilities assigned were the least satisfactory aspect of the report and that we cannot conclude
Re: Treatment of Adults with Complications from Previous Hypospadias Surgery Myers JB, McAninch JW, Erickson BA, Breyer BN J Urol 2012;188:459–63 Expert’s summary: The authors looked at a database of 1127 patients who had undergone urethroplasty at a single institution by a single surgeon between 1980 and 2009. From this database, they did a retrospective review of 50 urethroplasty patients who had undergone previous hypospadias surgery and were >18 yr of age. Of the 50 men presenting with complications, 78% had undergone hypospadias surgery during childhood and 66% had multiple previous surgeries. The most common complications seen in this group were urethral stricture in 72% and urethral cutaneous fistula in 24%.
[1] Draisma G, Etzioni R, Tsodikov A, et al. Lead time and overdiagnosis in prostate-specific antigen screening: importance of methods and context. J Natl Cancer Inst 2009;101:374–83. [2] Pelzer AE, Bektic J, Akkad T, et al. Under diagnosis and over diagnosis of prostate cancer in a screening population with serum PSA 2 to 10 ng/ml. J Urol 2007;178:93–7. [3] Graif T, Loeb S, Roehl KA, et al. Underdiagnosis and over diagnosis of prostate cancer. J Urol 2007;178:88–92. [4] Sox HC. Quality of life and guidelines for PSA screening. N Engl J Med 2012;367:669–71. [5] Moyer VA, US Preventive Services Task Force. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2012;157:120–34. William J. Catalona Northwestern Medical Faculty Foundation, Chicago, IL, USA E-mail address: [email protected]. http://dx.doi.org/10.1016/j.eururo.2012.10.030
The authors presented a well-organized and thoughtful approach to the management of the various complications, depending on the site of the urethral stricture and the quality of the surrounding tissues. Despite this wellorganized approach, their initial success rate in the 50 individuals was only 50%; of the other 50%, half developed recurrent urethral stricture and half developed urethral cutaneous fistula. The conclusion drawn by the authors is that patients with complications following previous hypospadias repair must be committed to the possibility of several surgeries to manage long-term urethral problems. Expert’s comments: As more pediatric patients who have undergone hypospadias repair during childhood transition to adolescence and adulthood, it has become clear that what is initially considered a
181
EUROPEAN UROLOGY 63 (2013) 178–182
successful hypospadias repair is not always durable. As the authors point out, a number of individuals present in adulthood with complications following childhood hypospadias repair that are often difficult to deal with and that might require multiple surgical procedures for correction. The difficulty of dealing with hypospadias complications presenting in the adult is not new [1], and the concept of doing hypospadias repair in the adult population is also not new [2]. We have recently summarized the impact of childhood hypospadias surgery in adulthood [3]. In addition to the long-term issues outlined in the present article, there is a significant psychosocial impact on these individuals as they transition to adulthood. For many individuals, overall satisfaction with the cosmetic aspect of the repair does not always coincide with the observations of the surgeon. There are also long-term issues with micturition, ejaculation, and erectile function that have been published [4]. Whether or not a childhood hypospadias repair has any impact on reproduction is open to some question. With regard to micturition, adult hypospadias patients have significantly more urinary symptoms compared with adult controls, and generally, the more severe the primary lesion, the more severe and more frequent the micturition issues. In terms of cosmesis, a significant number of individuals consider their penile appearance to be abnormal. In terms of sexuality, adult hypospadias patients are generally reportedly less satisfied with sexual function when compared with controls. This lower satisfaction might be related to body image and low self-esteem. Erectile dysfunction is more prevalent in hypospadias patients when compared with controls, and patients who started with severe hypospadias report difficulties with ejaculation
Re: Radiotherapy with or without Chemotherapy in Muscle-invasive Bladder Cancer James ND, Hussain SA, Hall E, et al., BC2001 Investigators N Engl J Med 2012;366:1477–88 Experts’ summary: The UK BC2001 investigators conducted a multicenter randomized phase 3 trial between 2001 and 2008 (median follow-up: 5.8 yr) comparing radiation alone versus concurrent chemoradiation with fluorouracil (5-FU)/mitomycin C (MMC) in 360 muscle-invasive bladder cancer patients (median age: 72 yr). There was a significant improvement in 2-yr locoregional disease-free survival (primary end point) for chemoradiation (67% vs 54%; hazard ratio [HR]: 0.68; p = 0.03) and in metastasis-free survival (HR: 0.72; p = 0.04). Although overall survival (48% vs 35%; HR: 0.82; p = 0.16) and disease-free survival (HR: 0.78; p = 0.09) trended in favor of chemoradiation, they were not significantly different. Chemoradiation was associated with a significant decrease in invasive recurrences (HR: 0.57; p = 0.01) and with a trend toward a reduction in the need for salvage cystectomy (HR: 0.58; p = 0.07). Acute gastrointestinal toxicity was worse with chemoradiation (grade 3–4, 9.6% vs 2.7%; p = 0.007); however, acute genitourinary (21.3% vs 21.4%; p = 0.99) and late Radiation
in greater numbers than controls. In terms of relationships, adult patients born with severe hypospadias have fewer intimate relations, lower self-esteem, negative genital appraisal, and inhibition in sexual contact when compared with controls. The bottom line is that, in terms of hypospadias, long-term follow-up and evaluation is often mandatory. Studies looking at the long-term effects of hypospadias repair in childhood using modern techniques are scarce. Hopefully, the newer techniques, which are being utilized today, will improve the overall functional and cosmetic results long term. Conflicts of interest: The author has nothing to disclose.
References [1] Mundy AR. Failed hypospadias repair presenting in adults. Eur Urol 2006;49:774–6. [2] Hensle TW, Tennenbaum SY, Reiley EA, Pollard J. Hypospadias repair in adults: adventures and misadventures. J Urol 2001;165:77–9. [3] Hensle TW, Deibert CM. Adult male health risks associated with congenital abnormalities. Urol Clin North Am 2012;39:109–14. [4] Rynja SP, de Jong TP, Bosch JL, de Kort LM. Functional, cosmetic and psychosexual results in adult men who underwent hypospadias correction in childhood. J Pediatr Urol 2011;7:504–15.
Terry W. Hensle Columbia University College of Physicians and Surgeons, New York, NY, USA E-mail address: [email protected]. http://dx.doi.org/10.1016/j.eururo.2012.10.031
Therapy Oncology Group (8.3% vs 15.7%; p = 0.07) grade 3–4 toxicity were similar. Experts’ comments: Bigger bang for the buck in bladder cancer! This landmark trial provides level 1 evidence demonstrating superiority of chemoradiation over radiation alone for invasive bladder cancer and is the largest such evaluation. It is practice confirming rather than changing, given that the introduction of concurrent radiosensitizing chemotherapy into bladder-preserving strategies has been evaluated and utilized for the past three decades [1]. The results are consistent with recent updated institutional reports [2] and comparable with large contemporary radical cystectomy series [3]. Although the choice of a locoregional control primary end point for this trial is justifiable, we look forward to longer follow-up to further address survival outcomes and the impact of radiation schedules/ design (as well as neoadjuvant chemotherapy) on disease control and toxicity. The study, however, may not be powered to comment adequately on these issues. There has never been a successful randomized comparison between combined-modality therapy and the gold standard primary cystectomy; however, other malignancies such as anal cancer have set precedent for adopting organ-sparing strategies using concurrent chemoradiation
EUROPEAN UROLOGY 63 (2013) 178–182
Re: Quality-of-life Effects of Prostate-specific Antigen Screening Heijnsdijk EA, Wever EM, Auvinen A, et al. N Engl J Med 2012;367:595–605 Expert’s summary: This report used decision modeling to quantify how the benefits of prostate cancer (PCa) screening is counterbalanced by the harms. The authors used data from the European Randomized Study of Screening for Prostate Cancer to predict outcomes under various scenarios. They report that annual screening of men aged 55–69 yr would result in a 28% decrease in PCa deaths, a 35% decrease in palliative treatments, and a total of 73 life-years gained per 1000 men screened (average 8.4 yr per death avoided). However, they discounted the gain by 23% because of offsetting treatment complications, that is, the gain was 56 quality-adjusted life-years (QALYs). To prevent one death, 98 men must be screened and five cancers detected. Screening men aged 55–74 yr resulted in 82 lifeyears gained but the same 56 QALYs.
that most patients will gain from screening because we do not know how many have lower versus higher utilities. If we knew that all have utilities consistent with a gain, then we could recommend universal screening. The US Preventive Services Task Force has recommended against screening in all men [5]. Sox stated that until we know the distribution of utilities for all health states, guidelines should avoid recommending for or against PSA screening but rather should recommend a shared decision process that includes assessing patients’ feelings about what they could go through after screening. In other words, the task force was wrong to downgrade the PSA screening recommendation. Conflicts of interest: The author has received research support and honoraria for speaking from and been an investigator for BeckmanCoulter Inc., has received research support and royalties as co-inventor from and been an investigator and consultant for OHMX Inc., has received research support from and been an investigator for deCODE genetics Inc., and has been an investigator for Nanosphere.
References Expert’s comments: If assumptions used in decision modeling are invalid, they fail to predict reality. Based on European data, the authors assumed that 43% of cancers were overdiagnosed. This is higher than estimates from US models (23–28% [1]) or surgical data (7–20% [2,3]). The authors attempt to quantify the trade-offs by expressing both benefits and harms in life-years. Sox’s accompanying editorial points out that this is like comparing apples and oranges [4]. The years gained by avoiding a PCa death is an objective assessment, but conversion of how a man feels about the number of years of life he would trade to avoid possible future complications he has never experienced (utilities) remains subjective. The cold truth is that it is easier said than done: ‘‘Would you rather live for 6 years with normal continence or for 14 years with a 10% chance of having to wear a pad? How about 7 versus 13?’’ Sox cautioned that the utilities assigned were the least satisfactory aspect of the report and that we cannot conclude
Re: Treatment of Adults with Complications from Previous Hypospadias Surgery Myers JB, McAninch JW, Erickson BA, Breyer BN J Urol 2012;188:459–63 Expert’s summary: The authors looked at a database of 1127 patients who had undergone urethroplasty at a single institution by a single surgeon between 1980 and 2009. From this database, they did a retrospective review of 50 urethroplasty patients who had undergone previous hypospadias surgery and were >18 yr of age. Of the 50 men presenting with complications, 78% had undergone hypospadias surgery during childhood and 66% had multiple previous surgeries. The most common complications seen in this group were urethral stricture in 72% and urethral cutaneous fistula in 24%.
[1] Draisma G, Etzioni R, Tsodikov A, et al. Lead time and overdiagnosis in prostate-specific antigen screening: importance of methods and context. J Natl Cancer Inst 2009;101:374–83. [2] Pelzer AE, Bektic J, Akkad T, et al. Under diagnosis and over diagnosis of prostate cancer in a screening population with serum PSA 2 to 10 ng/ml. J Urol 2007;178:93–7. [3] Graif T, Loeb S, Roehl KA, et al. Underdiagnosis and over diagnosis of prostate cancer. J Urol 2007;178:88–92. [4] Sox HC. Quality of life and guidelines for PSA screening. N Engl J Med 2012;367:669–71. [5] Moyer VA, US Preventive Services Task Force. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2012;157:120–34. William J. Catalona Northwestern Medical Faculty Foundation, Chicago, IL, USA E-mail address: [email protected]. http://dx.doi.org/10.1016/j.eururo.2012.10.030
The authors presented a well-organized and thoughtful approach to the management of the various complications, depending on the site of the urethral stricture and the quality of the surrounding tissues. Despite this wellorganized approach, their initial success rate in the 50 individuals was only 50%; of the other 50%, half developed recurrent urethral stricture and half developed urethral cutaneous fistula. The conclusion drawn by the authors is that patients with complications following previous hypospadias repair must be committed to the possibility of several surgeries to manage long-term urethral problems. Expert’s comments: As more pediatric patients who have undergone hypospadias repair during childhood transition to adolescence and adulthood, it has become clear that what is initially considered a
181
EUROPEAN UROLOGY 63 (2013) 178–182
successful hypospadias repair is not always durable. As the authors point out, a number of individuals present in adulthood with complications following childhood hypospadias repair that are often difficult to deal with and that might require multiple surgical procedures for correction. The difficulty of dealing with hypospadias complications presenting in the adult is not new [1], and the concept of doing hypospadias repair in the adult population is also not new [2]. We have recently summarized the impact of childhood hypospadias surgery in adulthood [3]. In addition to the long-term issues outlined in the present article, there is a significant psychosocial impact on these individuals as they transition to adulthood. For many individuals, overall satisfaction with the cosmetic aspect of the repair does not always coincide with the observations of the surgeon. There are also long-term issues with micturition, ejaculation, and erectile function that have been published [4]. Whether or not a childhood hypospadias repair has any impact on reproduction is open to some question. With regard to micturition, adult hypospadias patients have significantly more urinary symptoms compared with adult controls, and generally, the more severe the primary lesion, the more severe and more frequent the micturition issues. In terms of cosmesis, a significant number of individuals consider their penile appearance to be abnormal. In terms of sexuality, adult hypospadias patients are generally reportedly less satisfied with sexual function when compared with controls. This lower satisfaction might be related to body image and low self-esteem. Erectile dysfunction is more prevalent in hypospadias patients when compared with controls, and patients who started with severe hypospadias report difficulties with ejaculation
Re: Radiotherapy with or without Chemotherapy in Muscle-invasive Bladder Cancer James ND, Hussain SA, Hall E, et al., BC2001 Investigators N Engl J Med 2012;366:1477–88 Experts’ summary: The UK BC2001 investigators conducted a multicenter randomized phase 3 trial between 2001 and 2008 (median follow-up: 5.8 yr) comparing radiation alone versus concurrent chemoradiation with fluorouracil (5-FU)/mitomycin C (MMC) in 360 muscle-invasive bladder cancer patients (median age: 72 yr). There was a significant improvement in 2-yr locoregional disease-free survival (primary end point) for chemoradiation (67% vs 54%; hazard ratio [HR]: 0.68; p = 0.03) and in metastasis-free survival (HR: 0.72; p = 0.04). Although overall survival (48% vs 35%; HR: 0.82; p = 0.16) and disease-free survival (HR: 0.78; p = 0.09) trended in favor of chemoradiation, they were not significantly different. Chemoradiation was associated with a significant decrease in invasive recurrences (HR: 0.57; p = 0.01) and with a trend toward a reduction in the need for salvage cystectomy (HR: 0.58; p = 0.07). Acute gastrointestinal toxicity was worse with chemoradiation (grade 3–4, 9.6% vs 2.7%; p = 0.007); however, acute genitourinary (21.3% vs 21.4%; p = 0.99) and late Radiation
in greater numbers than controls. In terms of relationships, adult patients born with severe hypospadias have fewer intimate relations, lower self-esteem, negative genital appraisal, and inhibition in sexual contact when compared with controls. The bottom line is that, in terms of hypospadias, long-term follow-up and evaluation is often mandatory. Studies looking at the long-term effects of hypospadias repair in childhood using modern techniques are scarce. Hopefully, the newer techniques, which are being utilized today, will improve the overall functional and cosmetic results long term. Conflicts of interest: The author has nothing to disclose.
References [1] Mundy AR. Failed hypospadias repair presenting in adults. Eur Urol 2006;49:774–6. [2] Hensle TW, Tennenbaum SY, Reiley EA, Pollard J. Hypospadias repair in adults: adventures and misadventures. J Urol 2001;165:77–9. [3] Hensle TW, Deibert CM. Adult male health risks associated with congenital abnormalities. Urol Clin North Am 2012;39:109–14. [4] Rynja SP, de Jong TP, Bosch JL, de Kort LM. Functional, cosmetic and psychosexual results in adult men who underwent hypospadias correction in childhood. J Pediatr Urol 2011;7:504–15.
Terry W. Hensle Columbia University College of Physicians and Surgeons, New York, NY, USA E-mail address: [email protected]. http://dx.doi.org/10.1016/j.eururo.2012.10.031
Therapy Oncology Group (8.3% vs 15.7%; p = 0.07) grade 3–4 toxicity were similar. Experts’ comments: Bigger bang for the buck in bladder cancer! This landmark trial provides level 1 evidence demonstrating superiority of chemoradiation over radiation alone for invasive bladder cancer and is the largest such evaluation. It is practice confirming rather than changing, given that the introduction of concurrent radiosensitizing chemotherapy into bladder-preserving strategies has been evaluated and utilized for the past three decades [1]. The results are consistent with recent updated institutional reports [2] and comparable with large contemporary radical cystectomy series [3]. Although the choice of a locoregional control primary end point for this trial is justifiable, we look forward to longer follow-up to further address survival outcomes and the impact of radiation schedules/ design (as well as neoadjuvant chemotherapy) on disease control and toxicity. The study, however, may not be powered to comment adequately on these issues. There has never been a successful randomized comparison between combined-modality therapy and the gold standard primary cystectomy; however, other malignancies such as anal cancer have set precedent for adopting organ-sparing strategies using concurrent chemoradiation