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IH is even higher because a significant proportion of men elect not to have the hernia repaired. Another underreported complication is failed IH repair, reported at 32–63% [1]. What to do? On the surface, one could simply propose improvements in surgical technique or skill. When analysis of potential surgeon variables is performed (eg, surgeon, training level, and experience and volume), there is no statistical correlation; however, patient variables have been significantly associated, including age, Charlson comorbidity index, and prostate size (a surrogate for incision length). This suggests that, regardless of surgeon skill or technique, patient variables drive the risk of vertical IHs above the navel. For transverse versus vertical incision, a most pragmatic solution could be simply turning the incision 908. Physics supports the argument because when patients strain, lateral tensions to a vertical closure would pull apart, whereas a transverse incision would pull together. In 2011, we published that changing the orientation of the midline camera port from vertical to transverse dramatically reduced the incidence of IHs from 5.3% to 0.6% and reduced scar width from 5.5 mm to 2.0 mm ( p < 0.0001) [2]. The physics (ie, physical forces) and the deductive physical evidence (scar width) strongly suggest that following the physics and turning the incision 908 should (nearly) eliminate the problem. In medicine, the randomized controlled trial is the gold standard of medical evidence. In 2001, Grantcharov and Rosenberg published a review of 11 randomized controlled trials [3], and then more recently, in 2005, Brown and Goodfellow performed a Cochrane review of 16 randomized
controlled trials [4], and both demonstrated superiority of transverse over vertical incisions, with reduced pain, pulmonary complications, scar cosmesis, rupture, and IHs. A vertical incision is simple to perform and requires the same length of incision, and the evidence supports it.
Re: A Randomized Trial of Robot-assisted Laparoscopic Radical Cystectomy Bochner BH, Sjoberg DD, Laudone VP; Memorial Sloan Kettering Cancer Center Bladder Cancer Surgical Trials Group
radical cystectomy [1]. Prior successful experience with robotic prostate surgery, without compromising oncologic outcomes, has naturally resulted in a growing interest in applying these skills to bladder cancer. On its face, this study would seem to negate a significant driver for applying robotic surgery to lower complications; however, the fact that urinary diversions were performed via open surgery in both arms may explain why a benefit was not seen. A European study comparing open and robotic urinary diversion demonstrated not only equivalent safety and efficacy but also a 32% reduction in complications at 90 d [2]. It stands to reason that the study design of Bochner et al was bound to show futility from the outset. It is also unclear why an open approach to urinary diversion was chosen for all patients. Desai and colleagues recently presented their experience with robotic neobladders in >130 patients with results comparable to open series [3]. We have also experienced little difficulty adopting robotic surgery to intracorporeal conduits. Finally, by opting to present their data in a letter to the editor, granular details were lacking. Although Bochner et al discuss a modest reduction in blood loss, the details regarding complication type are not described. If the distribution of grade 3–5 complications were skewed toward higher-grade complications in the open arm, that would challenge their conclusions.
N Engl J Med 2014;371:389–90 Experts’ summary: Recently Bochner and colleagues from Memorial Sloan Kettering Cancer Center published a randomized trial of 118 patients, comparing complications 90 d after robotic radical cystectomy (RRC) or open radical cystectomy (ORC). The primary aim of their study was to compare 90-d complications (Clavien grade 2) in patients treated with radical cystectomy. Those who enrolled were randomized to either ORC and urinary diversion or RRC and open urinary diversion. In both arms, only experienced surgeons (10 yr of postfellowship experience) and robotic surgeries performed by clinicians experienced in pelvic robotic surgery were included. No benefit was seen in the robotic surgery arm when analyzed for overall complications (Clavien grade 2–5; 62% RRC vs 66% ORC) or for high-grade complications (Clavien 3–5; 22% RRC vs 21% ORC). Interim analysis demonstrated futility, and the study was closed. Experts’ comments: The authors should be applauded for conducting a prospective randomized trial to examine the utility of RRC. Efforts are needed to lower the high complication rates seen following
Conflicts of interest: The authors have nothing to disclose.
References [1] Burger JW, Luijendijk RW, Hop WC, et al. Long-term follow-up of a randomized controlled trial of suture versus mesh repair of incisional hernias. Ann Surg 2004;240:578–85. [2] Beck S, Skarecky D, Osann K, Juarez R, Ahlering TE. Transverse versus vertical camera port incision in robotic radical prostatectomy: effect on incisional hernias and cosmesis. Urology 2011;78:586–90. [3] Grantcharov TP, Rosenberg J. Vertical compared with transverse incisions in abdominal surgery. Eur J Surg 2001;167:260–7. [4] Brown SR, Goodfellow PB. Transverse versus midline incision for abdominal surgery. Cochrane Database Syst Rev 2005:CD005199. Thomas E. Ahlering*, Blanca E. Morales Department of Urology, University of California, Irvine Medical Center, Orange, CA, USA *Corresponding author. Department of Urology, University of California, Irvine Medical Center, 333 City Boulevard West Suite 2100, Orange, CA 92868-3298, USA. E-mail address: [email protected] (T.E. Ahlering).
http://dx.doi.org/10.1016/j.eururo.2014.09.045
Conflicts of interest: The authors have nothing to disclose.
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References
Neema Navai, Surena F. Matin* The University of Texas M.D. Anderson Cancer Center,
[1] Svatek RS, Fisher MB, Matin SF, et al. Risk factor analysis in a
Houston, TX, USA
contemporary cystectomy cohort using standardized reporting methodology and adverse event criteria. J Urol 2010;183:929–34. [2] Ahmed K, Khan SA, Hayn MH, et al. Analysis of intracorporeal
*Corresponding author. Department of Urology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd.,
compared with extracorporeal urinary diversion after robot-
Unit 1373, Houston, TX 77030, USA.
assisted radical cystectomy: results from the International Robotic
E-mail address: [email protected] (S.F. Matin).
Cystectomy Consortium. Eur Urol 2014;65:340–7. [3] Desai MM, Gill IS, de Castro Abreu AL, et al. Robotic intracorporeal orthotopic neobladder during radical cystectomy in 132 patients. J Urol. In press. http://dx.doi.org/10.1016/j.juro.2014.06.087.
Re: Enzalutamide in Metastatic Prostate Cancer Before Chemotherapy Beer TM, Armstrong AJ, Rathkopf DE, et al; PREVAIL Investigators N Engl J Med 2014;371:424–33 Experts’ summary: Enzalutamide is an oral second-generation androgen-receptor inhibitor that was demonstrated to prolong survival in men with castrate-resistant prostate cancer (CRPC) who had progressed following cytotoxic chemotherapy [1]. PREVAIL, A Safety and Efficacy Study of Oral MDV3100 in Chemotherapy-Naive Patients With Progressive Metastatic Prostate Cancer, is a multinational, double-blind, randomized, placebocontrolled, phase 3 trial evaluating the use of enzalutamide in CRPC patients who have not received chemotherapy. The investigators hoped to prove that earlier treatment would further improve survival. The study enrolled 1717 patients, 872 in the experimental arm and 845 in the control arm. Both co–primary end points (overall survival [OS] and radiographic progression-free survival [PFS]) were met. At the 12-mo followup, the investigators demonstrated a 65% rate of PFS in the enzalutamide arm compared with 14% in the placebo arm (hazard ratio [HR]: 0.19; 95% confidence interval [CI], 0.15– 0.23; p < 0.001). OS analysis revealed a 29% decreased risk of death in the enzalutamide arm (HR: 0.71; 95% CI, 0.60–0.84; p < 0.001). Subsequent therapy was less frequent, with only 40% of patients in the enzalutamide arm receiving additional antineoplastic therapy compared with 70% in the placebo arm. Experts’ comments: The management of advanced prostate cancer continues to improve and, at the same time, become more complicated. Within the past decade, six new treatments have become available for the treatment of CRPC [2]. Although the survival advantages have been modest, efforts are directed increasingly toward earlier treatment when, theoretically, the survival advantage should be longer. The PREVAIL trial fits into this paradigm and should be viewed as a success. In addition to significantly decreased risk of death and radiographic progression, enzalutamide displayed benefit for all secondary end points studied including prostate-specific antigen progression, time to chemotherapy, and metastatic soft tissue response. Maintaining quality of life can be just as important as prolonging survival in metastatic prostate cancer. Fortunately,
http://dx.doi.org/10.1016/j.eururo.2014.09.046
enzalutamide was shown to be well tolerated; the main adverse effects were related to profound androgen deprivation (ie, fatigue and hot flashes) [1]. With the addition of enzalutamide, clinicians now have several therapeutic options for men with CRPC who have not received chemotherapy, including aberaterone and docetaxel, both of which have been shown to prolong survival in the same population [2]. Furthermore, recent unpublished data suggest that docetaxel should be given even earlier in the disease course for androgen-sensitive disease [3]. These therapeutic agents have varied mechanisms of action, and their combined use, either concomitantly or sequentially, may provide an even greater survival benefit. Additional studies are needed and are currently under way to parse the optimal treatment timing and regimen for CRPC, specifically, and for advanced prostate cancer in general [4]. Until these trials are completed, we are left wondering which treatment should be given in what order. Still, this is a better problem to have than having no effective treatment at all. Conflicts of interest: Dr. Adam Kibel is affiliated with Sanofi Aventis, Dendreon, and Oncotype DX. Dr. Adam Althaus has nothing to disclose.
References [1] Scher HI, Fizazi K, Saad F, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 2012;367:1187–97. [2] Cookson MS, Roth BJ, Dahm P, et al. Castrate-resistant prostate cancer: AUA Guideline. J Urol 2013;190:429–38. [3] Sweeney C, Chen Y, Carducci MA, et al. Impact on overall survival (OS) with chemohormonal therapy versus hormonal therapy for hormone-sensitive newly metastatic prostate cancer (mPrCa): an ECOG-led phase III randomized trial. Presented at: American Society of Clinical Oncology annual meeting; June 1, 2014; Chicago, IL. [4] Attard G, Sydes MR, Mason MD, et al. Combining enzalutamide with abiraterone, prednisone, and androgen deprivation therapy in the STAMPEDE trial. Eur Urol 2014;66:799–802. Adam Althaus, Adam Kibel* Department of Urology, Brigham and Women’s Hospital, Boston, MA, USA *Corresponding author. Department of Urology, Brigham and Women’s Hospital, 45 Francis Street, Boston, MA 02115, USA. E-mail address: [email protected] (A. Kibel).
http://dx.doi.org/10.1016/j.eururo.2014.09.047
EUROPEAN UROLOGY 67 (2015) 171–175
IH is even higher because a significant proportion of men elect not to have the hernia repaired. Another underreported complication is failed IH repair, reported at 32–63% [1]. What to do? On the surface, one could simply propose improvements in surgical technique or skill. When analysis of potential surgeon variables is performed (eg, surgeon, training level, and experience and volume), there is no statistical correlation; however, patient variables have been significantly associated, including age, Charlson comorbidity index, and prostate size (a surrogate for incision length). This suggests that, regardless of surgeon skill or technique, patient variables drive the risk of vertical IHs above the navel. For transverse versus vertical incision, a most pragmatic solution could be simply turning the incision 908. Physics supports the argument because when patients strain, lateral tensions to a vertical closure would pull apart, whereas a transverse incision would pull together. In 2011, we published that changing the orientation of the midline camera port from vertical to transverse dramatically reduced the incidence of IHs from 5.3% to 0.6% and reduced scar width from 5.5 mm to 2.0 mm ( p < 0.0001) [2]. The physics (ie, physical forces) and the deductive physical evidence (scar width) strongly suggest that following the physics and turning the incision 908 should (nearly) eliminate the problem. In medicine, the randomized controlled trial is the gold standard of medical evidence. In 2001, Grantcharov and Rosenberg published a review of 11 randomized controlled trials [3], and then more recently, in 2005, Brown and Goodfellow performed a Cochrane review of 16 randomized
controlled trials [4], and both demonstrated superiority of transverse over vertical incisions, with reduced pain, pulmonary complications, scar cosmesis, rupture, and IHs. A vertical incision is simple to perform and requires the same length of incision, and the evidence supports it.
Re: A Randomized Trial of Robot-assisted Laparoscopic Radical Cystectomy Bochner BH, Sjoberg DD, Laudone VP; Memorial Sloan Kettering Cancer Center Bladder Cancer Surgical Trials Group
radical cystectomy [1]. Prior successful experience with robotic prostate surgery, without compromising oncologic outcomes, has naturally resulted in a growing interest in applying these skills to bladder cancer. On its face, this study would seem to negate a significant driver for applying robotic surgery to lower complications; however, the fact that urinary diversions were performed via open surgery in both arms may explain why a benefit was not seen. A European study comparing open and robotic urinary diversion demonstrated not only equivalent safety and efficacy but also a 32% reduction in complications at 90 d [2]. It stands to reason that the study design of Bochner et al was bound to show futility from the outset. It is also unclear why an open approach to urinary diversion was chosen for all patients. Desai and colleagues recently presented their experience with robotic neobladders in >130 patients with results comparable to open series [3]. We have also experienced little difficulty adopting robotic surgery to intracorporeal conduits. Finally, by opting to present their data in a letter to the editor, granular details were lacking. Although Bochner et al discuss a modest reduction in blood loss, the details regarding complication type are not described. If the distribution of grade 3–5 complications were skewed toward higher-grade complications in the open arm, that would challenge their conclusions.
N Engl J Med 2014;371:389–90 Experts’ summary: Recently Bochner and colleagues from Memorial Sloan Kettering Cancer Center published a randomized trial of 118 patients, comparing complications 90 d after robotic radical cystectomy (RRC) or open radical cystectomy (ORC). The primary aim of their study was to compare 90-d complications (Clavien grade 2) in patients treated with radical cystectomy. Those who enrolled were randomized to either ORC and urinary diversion or RRC and open urinary diversion. In both arms, only experienced surgeons (10 yr of postfellowship experience) and robotic surgeries performed by clinicians experienced in pelvic robotic surgery were included. No benefit was seen in the robotic surgery arm when analyzed for overall complications (Clavien grade 2–5; 62% RRC vs 66% ORC) or for high-grade complications (Clavien 3–5; 22% RRC vs 21% ORC). Interim analysis demonstrated futility, and the study was closed. Experts’ comments: The authors should be applauded for conducting a prospective randomized trial to examine the utility of RRC. Efforts are needed to lower the high complication rates seen following
Conflicts of interest: The authors have nothing to disclose.
References [1] Burger JW, Luijendijk RW, Hop WC, et al. Long-term follow-up of a randomized controlled trial of suture versus mesh repair of incisional hernias. Ann Surg 2004;240:578–85. [2] Beck S, Skarecky D, Osann K, Juarez R, Ahlering TE. Transverse versus vertical camera port incision in robotic radical prostatectomy: effect on incisional hernias and cosmesis. Urology 2011;78:586–90. [3] Grantcharov TP, Rosenberg J. Vertical compared with transverse incisions in abdominal surgery. Eur J Surg 2001;167:260–7. [4] Brown SR, Goodfellow PB. Transverse versus midline incision for abdominal surgery. Cochrane Database Syst Rev 2005:CD005199. Thomas E. Ahlering*, Blanca E. Morales Department of Urology, University of California, Irvine Medical Center, Orange, CA, USA *Corresponding author. Department of Urology, University of California, Irvine Medical Center, 333 City Boulevard West Suite 2100, Orange, CA 92868-3298, USA. E-mail address: [email protected] (T.E. Ahlering).
http://dx.doi.org/10.1016/j.eururo.2014.09.045
Conflicts of interest: The authors have nothing to disclose.
174
EUROPEAN UROLOGY 67 (2015) 171–175
References
Neema Navai, Surena F. Matin* The University of Texas M.D. Anderson Cancer Center,
[1] Svatek RS, Fisher MB, Matin SF, et al. Risk factor analysis in a
Houston, TX, USA
contemporary cystectomy cohort using standardized reporting methodology and adverse event criteria. J Urol 2010;183:929–34. [2] Ahmed K, Khan SA, Hayn MH, et al. Analysis of intracorporeal
*Corresponding author. Department of Urology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd.,
compared with extracorporeal urinary diversion after robot-
Unit 1373, Houston, TX 77030, USA.
assisted radical cystectomy: results from the International Robotic
E-mail address: [email protected] (S.F. Matin).
Cystectomy Consortium. Eur Urol 2014;65:340–7. [3] Desai MM, Gill IS, de Castro Abreu AL, et al. Robotic intracorporeal orthotopic neobladder during radical cystectomy in 132 patients. J Urol. In press. http://dx.doi.org/10.1016/j.juro.2014.06.087.
Re: Enzalutamide in Metastatic Prostate Cancer Before Chemotherapy Beer TM, Armstrong AJ, Rathkopf DE, et al; PREVAIL Investigators N Engl J Med 2014;371:424–33 Experts’ summary: Enzalutamide is an oral second-generation androgen-receptor inhibitor that was demonstrated to prolong survival in men with castrate-resistant prostate cancer (CRPC) who had progressed following cytotoxic chemotherapy [1]. PREVAIL, A Safety and Efficacy Study of Oral MDV3100 in Chemotherapy-Naive Patients With Progressive Metastatic Prostate Cancer, is a multinational, double-blind, randomized, placebocontrolled, phase 3 trial evaluating the use of enzalutamide in CRPC patients who have not received chemotherapy. The investigators hoped to prove that earlier treatment would further improve survival. The study enrolled 1717 patients, 872 in the experimental arm and 845 in the control arm. Both co–primary end points (overall survival [OS] and radiographic progression-free survival [PFS]) were met. At the 12-mo followup, the investigators demonstrated a 65% rate of PFS in the enzalutamide arm compared with 14% in the placebo arm (hazard ratio [HR]: 0.19; 95% confidence interval [CI], 0.15– 0.23; p < 0.001). OS analysis revealed a 29% decreased risk of death in the enzalutamide arm (HR: 0.71; 95% CI, 0.60–0.84; p < 0.001). Subsequent therapy was less frequent, with only 40% of patients in the enzalutamide arm receiving additional antineoplastic therapy compared with 70% in the placebo arm. Experts’ comments: The management of advanced prostate cancer continues to improve and, at the same time, become more complicated. Within the past decade, six new treatments have become available for the treatment of CRPC [2]. Although the survival advantages have been modest, efforts are directed increasingly toward earlier treatment when, theoretically, the survival advantage should be longer. The PREVAIL trial fits into this paradigm and should be viewed as a success. In addition to significantly decreased risk of death and radiographic progression, enzalutamide displayed benefit for all secondary end points studied including prostate-specific antigen progression, time to chemotherapy, and metastatic soft tissue response. Maintaining quality of life can be just as important as prolonging survival in metastatic prostate cancer. Fortunately,
http://dx.doi.org/10.1016/j.eururo.2014.09.046
enzalutamide was shown to be well tolerated; the main adverse effects were related to profound androgen deprivation (ie, fatigue and hot flashes) [1]. With the addition of enzalutamide, clinicians now have several therapeutic options for men with CRPC who have not received chemotherapy, including aberaterone and docetaxel, both of which have been shown to prolong survival in the same population [2]. Furthermore, recent unpublished data suggest that docetaxel should be given even earlier in the disease course for androgen-sensitive disease [3]. These therapeutic agents have varied mechanisms of action, and their combined use, either concomitantly or sequentially, may provide an even greater survival benefit. Additional studies are needed and are currently under way to parse the optimal treatment timing and regimen for CRPC, specifically, and for advanced prostate cancer in general [4]. Until these trials are completed, we are left wondering which treatment should be given in what order. Still, this is a better problem to have than having no effective treatment at all. Conflicts of interest: Dr. Adam Kibel is affiliated with Sanofi Aventis, Dendreon, and Oncotype DX. Dr. Adam Althaus has nothing to disclose.
References [1] Scher HI, Fizazi K, Saad F, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 2012;367:1187–97. [2] Cookson MS, Roth BJ, Dahm P, et al. Castrate-resistant prostate cancer: AUA Guideline. J Urol 2013;190:429–38. [3] Sweeney C, Chen Y, Carducci MA, et al. Impact on overall survival (OS) with chemohormonal therapy versus hormonal therapy for hormone-sensitive newly metastatic prostate cancer (mPrCa): an ECOG-led phase III randomized trial. Presented at: American Society of Clinical Oncology annual meeting; June 1, 2014; Chicago, IL. [4] Attard G, Sydes MR, Mason MD, et al. Combining enzalutamide with abiraterone, prednisone, and androgen deprivation therapy in the STAMPEDE trial. Eur Urol 2014;66:799–802. Adam Althaus, Adam Kibel* Department of Urology, Brigham and Women’s Hospital, Boston, MA, USA *Corresponding author. Department of Urology, Brigham and Women’s Hospital, 45 Francis Street, Boston, MA 02115, USA. E-mail address: [email protected] (A. Kibel).
http://dx.doi.org/10.1016/j.eururo.2014.09.047
