Recurrence Patterns After Open and Robot-assisted Radical Cystectomy for Bladder Cancer

Oncologic efficacy remains the standard that will ultimately verify the true value of RARC. Concerns about proper oncologic resection and the possibility that pneumoperitoneum enhances tumor cell dissemination prompted our precise analysis of recurrence patterns after ORC and RARC, while bearing in mind that selection bias accounted for baseline differences between the two groups.

In this study, we detected 15/65 (23%) and 24/136 (18%) local recurrences within 2 yr of surgery in ORC and RARC patients, respectively. In agreement with ORC series, patients who developed local recurrence in the current study usually did so within the first 18 mo after surgery [19], [20], and [21]. Nevertheless, the relatively small number of patients does not preclude the possibility of differences between the two surgical techniques with regard to local recurrence. Importantly, selection bias was present, as patients undergoing ORC presented with higher clinical and pathologic stages.

The most interesting finding with regard to metastases is the distribution of distant recurrence locations between ORC and RARC. The most frequent locations remained the lungs, liver, and bone, which is consistent with the pattern of metastasis seen in autopsy studies and previous clinical series [21], [22], [23], and [24]. However, extrapelvic lymph node locations were more frequent for RARC than for ORC in patients with distant recurrence (10/43 [23%] vs 4/26 [15%]). It is often suggested that the maneuverability of the robotic system may limit the ability to perform a thorough extended PLND. However, we believe that our robot-assisted PLND technique adheres to the same oncologic standards and anatomic boundaries as our open technique. In this study, the median number of lymph nodes removed did not significantly differ between ORC and RARC (20 vs 21). Of course, it is still possible that factors related to the dissection technique are responsible for the current findings. Nevertheless, all of the extrapelvic lymph node recurrences were, by definition, outside the primary extended PLND template, regardless of whether an open or robotic approach was used. One possible explanation for the higher number of extrapelvic lymph node recurrences could be variant lymphatic dissemination as a result of the robotic technique. The true answer to this is not known, however, and the results remain intriguing.

Similarly, peritoneal carcinomatosis was more frequent in RARC patients than in ORC patients with distant recurrence (9/43 [21%] vs 2/26 [8%]). Laparoscopic surgery has been associated with a minimal risk of peritoneal tumor spread through the effect of pneumoperitoneum [10] and [11]. Peritoneal carcinomatosis is found in 16–19% of BCa subjects in autopsy and clinical studies, albeit most often in association with extensive metastases at other locations [22] and [23], while peritoneal carcinomatosis was the sole location in more than half of our cases. However, eight of nine RARC patients who developed peritoneal carcinomatosis had pathologic stage ≥T3, supporting the notion that peritoneal carcinomatosis was more a reflection of cancer biology than a surgical issue. Although the numbers are too few for robust conclusions, our findings warrant further investigations. If differences in recurrence patterns indeed exist between RARC and ORC, we do not believe that the cause is related to the experience level of the surgeon, as most RARC patients with extrapelvic lymph node metastasis or peritoneal carcinomatosis were operated on from 2008 to 2012. Furthermore, precautionary measures are taken to prevent spillage of any malignant cells into the operative field. Following division of the anterior urethral wall, the Foley catheter is immediately clipped with a large Hem-o-lok clip and then cut distal to the clip to maintain the integrity of the balloon. The posterior urethral wall is divided, and the bladder and the indwelling Foley catheter are immediately placed in an Endo Catch bag, thus avoiding urinary extravasation or tumor spillage, which were never observed in this cohort.

Of note, within 2 yr of surgery no secondary urothelial carcinoma was detected in the ORC group, while only four cases were diagnosed in the RARC group. Previous reports have demonstrated that the median time to secondary urothelial carcinomas ranges from 3.3 to 4.3 yr [25] and [26], and rates of urinary tract recurrences are as low as 1.7% at 5 yr [19] . In accordance with our study design, we reported events within 2 yr of surgery. Moreover, the ORC group represented a smaller patient sample than the RARC group. These factors likely explain our findings.

Previous reports evaluating RARC included patients with few comorbidities and low disease burden [14], [27], and [28], which reflects the expected selection bias when a new surgical technique is introduced. Although in our experience these factors have become less important when discussing the surgical technique, selection bias certainly remains, and must be accounted for when drawing conclusions related to oncologic outcomes. The open approach remains the technique of choice in patients with larger tumors and unfavorable local tumor status, allowing easier intraoperative manipulation of specimens [29] . Although adjustment for baseline differences showed no evidence of an additional risk of recurrence in RARC patients, it should be kept in mind that multivariable analyses cannot account for all confounding factors in a data set. Moreover, the CI of the hazard ratio for recurrence is relatively wide, implying that an association between RARC and recurrence cannot be excluded with certainty. However, the fact that extrapelvic lymph node locations and peritoneal carcinomatosis were found more frequently in RARC patients, the cohort with less advanced disease, suggests that selection bias could also have attenuated differences. Potential variations in the use of perioperative chemotherapy are an additional limitation of the study. Taken together, our results are hypothesis-generating and should encourage discussions among urologists.

Open radical cystectomy (ORC) is the mainstay of therapy for patients with muscle-invasive and high-risk non–muscle-invasive bladder cancer (BCa) [1] . Following successful adoption of minimally invasive techniques in kidney and prostate surgery, the last few years have seen growing interest in robot-assisted radical cystectomy (RARC). In retrospective studies [2] and [3] and in the Memorial Sloan Kettering Cancer Center randomized trial [4] , large differences in complication rates between RARC and ORC have not been observed.

However, the introduction of RARC into surgical practice has been accompanied by legitimate concerns regarding its oncologic efficacy [5] . To date, favorable outcomes in terms of positive surgical margin (PSM) rates and lymph node yield have been published [2], [3], and [6]. Early oncologic outcomes appear to be acceptable [7], [8], and [9]. Nevertheless, the use of RARC remains controversial and restricted to specialized centers [3], [6], [7], and [9]. Furthermore, there is anecdotal evidence of peritoneal seeding during minimally invasive surgery [10] , and pneumoperitoneum may impact BCa cell seeding [11] .

In light of the possibility of unusual recurrence locations after RARC, limited information is available for the robotic approach with regard to patterns of disease recurrence. In the present study we describe recurrence patterns in patients who underwent ORC and RARC.

Oncologic efficacy remains the standard that will ultimately verify the true value of RARC. Concerns about proper oncologic resection and the possibility that pneumoperitoneum enhances tumor cell dissemination prompted our precise analysis of recurrence patterns after ORC and RARC, while bearing in mind that selection bias accounted for baseline differences between the two groups.

In this study, we detected 15/65 (23%) and 24/136 (18%) local recurrences within 2 yr of surgery in ORC and RARC patients, respectively. In agreement with ORC series, patients who developed local recurrence in the current study usually did so within the first 18 mo after surgery [19], [20], and [21]. Nevertheless, the relatively small number of patients does not preclude the possibility of differences between the two surgical techniques with regard to local recurrence. Importantly, selection bias was present, as patients undergoing ORC presented with higher clinical and pathologic stages.

The most interesting finding with regard to metastases is the distribution of distant recurrence locations between ORC and RARC. The most frequent locations remained the lungs, liver, and bone, which is consistent with the pattern of metastasis seen in autopsy studies and previous clinical series [21], [22], [23], and [24]. However, extrapelvic lymph node locations were more frequent for RARC than for ORC in patients with distant recurrence (10/43 [23%] vs 4/26 [15%]). It is often suggested that the maneuverability of the robotic system may limit the ability to perform a thorough extended PLND. However, we believe that our robot-assisted PLND technique adheres to the same oncologic standards and anatomic boundaries as our open technique. In this study, the median number of lymph nodes removed did not significantly differ between ORC and RARC (20 vs 21). Of course, it is still possible that factors related to the dissection technique are responsible for the current findings. Nevertheless, all of the extrapelvic lymph node recurrences were, by definition, outside the primary extended PLND template, regardless of whether an open or robotic approach was used. One possible explanation for the higher number of extrapelvic lymph node recurrences could be variant lymphatic dissemination as a result of the robotic technique. The true answer to this is not known, however, and the results remain intriguing.

Similarly, peritoneal carcinomatosis was more frequent in RARC patients than in ORC patients with distant recurrence (9/43 [21%] vs 2/26 [8%]). Laparoscopic surgery has been associated with a minimal risk of peritoneal tumor spread through the effect of pneumoperitoneum [10] and [11]. Peritoneal carcinomatosis is found in 16–19% of BCa subjects in autopsy and clinical studies, albeit most often in association with extensive metastases at other locations [22] and [23], while peritoneal carcinomatosis was the sole location in more than half of our cases. However, eight of nine RARC patients who developed peritoneal carcinomatosis had pathologic stage ≥T3, supporting the notion that peritoneal carcinomatosis was more a reflection of cancer biology than a surgical issue. Although the numbers are too few for robust conclusions, our findings warrant further investigations. If differences in recurrence patterns indeed exist between RARC and ORC, we do not believe that the cause is related to the experience level of the surgeon, as most RARC patients with extrapelvic lymph node metastasis or peritoneal carcinomatosis were operated on from 2008 to 2012. Furthermore, precautionary measures are taken to prevent spillage of any malignant cells into the operative field. Following division of the anterior urethral wall, the Foley catheter is immediately clipped with a large Hem-o-lok clip and then cut distal to the clip to maintain the integrity of the balloon. The posterior urethral wall is divided, and the bladder and the indwelling Foley catheter are immediately placed in an Endo Catch bag, thus avoiding urinary extravasation or tumor spillage, which were never observed in this cohort.

Of note, within 2 yr of surgery no secondary urothelial carcinoma was detected in the ORC group, while only four cases were diagnosed in the RARC group. Previous reports have demonstrated that the median time to secondary urothelial carcinomas ranges from 3.3 to 4.3 yr [25] and [26], and rates of urinary tract recurrences are as low as 1.7% at 5 yr [19] . In accordance with our study design, we reported events within 2 yr of surgery. Moreover, the ORC group represented a smaller patient sample than the RARC group. These factors likely explain our findings.

Previous reports evaluating RARC included patients with few comorbidities and low disease burden [14], [27], and [28], which reflects the expected selection bias when a new surgical technique is introduced. Although in our experience these factors have become less important when discussing the surgical technique, selection bias certainly remains, and must be accounted for when drawing conclusions related to oncologic outcomes. The open approach remains the technique of choice in patients with larger tumors and unfavorable local tumor status, allowing easier intraoperative manipulation of specimens [29] . Although adjustment for baseline differences showed no evidence of an additional risk of recurrence in RARC patients, it should be kept in mind that multivariable analyses cannot account for all confounding factors in a data set. Moreover, the CI of the hazard ratio for recurrence is relatively wide, implying that an association between RARC and recurrence cannot be excluded with certainty. However, the fact that extrapelvic lymph node locations and peritoneal carcinomatosis were found more frequently in RARC patients, the cohort with less advanced disease, suggests that selection bias could also have attenuated differences. Potential variations in the use of perioperative chemotherapy are an additional limitation of the study. Taken together, our results are hypothesis-generating and should encourage discussions among urologists.

Open radical cystectomy (ORC) is the mainstay of therapy for patients with muscle-invasive and high-risk non–muscle-invasive bladder cancer (BCa) [1] . Following successful adoption of minimally invasive techniques in kidney and prostate surgery, the last few years have seen growing interest in robot-assisted radical cystectomy (RARC). In retrospective studies [2] and [3] and in the Memorial Sloan Kettering Cancer Center randomized trial [4] , large differences in complication rates between RARC and ORC have not been observed.

However, the introduction of RARC into surgical practice has been accompanied by legitimate concerns regarding its oncologic efficacy [5] . To date, favorable outcomes in terms of positive surgical margin (PSM) rates and lymph node yield have been published [2], [3], and [6]. Early oncologic outcomes appear to be acceptable [7], [8], and [9]. Nevertheless, the use of RARC remains controversial and restricted to specialized centers [3], [6], [7], and [9]. Furthermore, there is anecdotal evidence of peritoneal seeding during minimally invasive surgery [10] , and pneumoperitoneum may impact BCa cell seeding [11] .

In light of the possibility of unusual recurrence locations after RARC, limited information is available for the robotic approach with regard to patterns of disease recurrence. In the present study we describe recurrence patterns in patients who underwent ORC and RARC.

Oncologic efficacy remains the standard that will ultimately verify the true value of RARC. Concerns about proper oncologic resection and the possibility that pneumoperitoneum enhances tumor cell dissemination prompted our precise analysis of recurrence patterns after ORC and RARC, while bearing in mind that selection bias accounted for baseline differences between the two groups.

In this study, we detected 15/65 (23%) and 24/136 (18%) local recurrences within 2 yr of surgery in ORC and RARC patients, respectively. In agreement with ORC series, patients who developed local recurrence in the current study usually did so within the first 18 mo after surgery [19], [20], and [21]. Nevertheless, the relatively small number of patients does not preclude the possibility of differences between the two surgical techniques with regard to local recurrence. Importantly, selection bias was present, as patients undergoing ORC presented with higher clinical and pathologic stages.

The most interesting finding with regard to metastases is the distribution of distant recurrence locations between ORC and RARC. The most frequent locations remained the lungs, liver, and bone, which is consistent with the pattern of metastasis seen in autopsy studies and previous clinical series [21], [22], [23], and [24]. However, extrapelvic lymph node locations were more frequent for RARC than for ORC in patients with distant recurrence (10/43 [23%] vs 4/26 [15%]). It is often suggested that the maneuverability of the robotic system may limit the ability to perform a thorough extended PLND. However, we believe that our robot-assisted PLND technique adheres to the same oncologic standards and anatomic boundaries as our open technique. In this study, the median number of lymph nodes removed did not significantly differ between ORC and RARC (20 vs 21). Of course, it is still possible that factors related to the dissection technique are responsible for the current findings. Nevertheless, all of the extrapelvic lymph node recurrences were, by definition, outside the primary extended PLND template, regardless of whether an open or robotic approach was used. One possible explanation for the higher number of extrapelvic lymph node recurrences could be variant lymphatic dissemination as a result of the robotic technique. The true answer to this is not known, however, and the results remain intriguing.

Similarly, peritoneal carcinomatosis was more frequent in RARC patients than in ORC patients with distant recurrence (9/43 [21%] vs 2/26 [8%]). Laparoscopic surgery has been associated with a minimal risk of peritoneal tumor spread through the effect of pneumoperitoneum [10] and [11]. Peritoneal carcinomatosis is found in 16–19% of BCa subjects in autopsy and clinical studies, albeit most often in association with extensive metastases at other locations [22] and [23], while peritoneal carcinomatosis was the sole location in more than half of our cases. However, eight of nine RARC patients who developed peritoneal carcinomatosis had pathologic stage ≥T3, supporting the notion that peritoneal carcinomatosis was more a reflection of cancer biology than a surgical issue. Although the numbers are too few for robust conclusions, our findings warrant further investigations. If differences in recurrence patterns indeed exist between RARC and ORC, we do not believe that the cause is related to the experience level of the surgeon, as most RARC patients with extrapelvic lymph node metastasis or peritoneal carcinomatosis were operated on from 2008 to 2012. Furthermore, precautionary measures are taken to prevent spillage of any malignant cells into the operative field. Following division of the anterior urethral wall, the Foley catheter is immediately clipped with a large Hem-o-lok clip and then cut distal to the clip to maintain the integrity of the balloon. The posterior urethral wall is divided, and the bladder and the indwelling Foley catheter are immediately placed in an Endo Catch bag, thus avoiding urinary extravasation or tumor spillage, which were never observed in this cohort.

Of note, within 2 yr of surgery no secondary urothelial carcinoma was detected in the ORC group, while only four cases were diagnosed in the RARC group. Previous reports have demonstrated that the median time to secondary urothelial carcinomas ranges from 3.3 to 4.3 yr [25] and [26], and rates of urinary tract recurrences are as low as 1.7% at 5 yr [19] . In accordance with our study design, we reported events within 2 yr of surgery. Moreover, the ORC group represented a smaller patient sample than the RARC group. These factors likely explain our findings.

Previous reports evaluating RARC included patients with few comorbidities and low disease burden [14], [27], and [28], which reflects the expected selection bias when a new surgical technique is introduced. Although in our experience these factors have become less important when discussing the surgical technique, selection bias certainly remains, and must be accounted for when drawing conclusions related to oncologic outcomes. The open approach remains the technique of choice in patients with larger tumors and unfavorable local tumor status, allowing easier intraoperative manipulation of specimens [29] . Although adjustment for baseline differences showed no evidence of an additional risk of recurrence in RARC patients, it should be kept in mind that multivariable analyses cannot account for all confounding factors in a data set. Moreover, the CI of the hazard ratio for recurrence is relatively wide, implying that an association between RARC and recurrence cannot be excluded with certainty. However, the fact that extrapelvic lymph node locations and peritoneal carcinomatosis were found more frequently in RARC patients, the cohort with less advanced disease, suggests that selection bias could also have attenuated differences. Potential variations in the use of perioperative chemotherapy are an additional limitation of the study. Taken together, our results are hypothesis-generating and should encourage discussions among urologists.

Open radical cystectomy (ORC) is the mainstay of therapy for patients with muscle-invasive and high-risk non–muscle-invasive bladder cancer (BCa) [1] . Following successful adoption of minimally invasive techniques in kidney and prostate surgery, the last few years have seen growing interest in robot-assisted radical cystectomy (RARC). In retrospective studies [2] and [3] and in the Memorial Sloan Kettering Cancer Center randomized trial [4] , large differences in complication rates between RARC and ORC have not been observed.

However, the introduction of RARC into surgical practice has been accompanied by legitimate concerns regarding its oncologic efficacy [5] . To date, favorable outcomes in terms of positive surgical margin (PSM) rates and lymph node yield have been published [2], [3], and [6]. Early oncologic outcomes appear to be acceptable [7], [8], and [9]. Nevertheless, the use of RARC remains controversial and restricted to specialized centers [3], [6], [7], and [9]. Furthermore, there is anecdotal evidence of peritoneal seeding during minimally invasive surgery [10] , and pneumoperitoneum may impact BCa cell seeding [11] .

In light of the possibility of unusual recurrence locations after RARC, limited information is available for the robotic approach with regard to patterns of disease recurrence. In the present study we describe recurrence patterns in patients who underwent ORC and RARC.

Oncologic efficacy remains the standard that will ultimately verify the true value of RARC. Concerns about proper oncologic resection and the possibility that pneumoperitoneum enhances tumor cell dissemination prompted our precise analysis of recurrence patterns after ORC and RARC, while bearing in mind that selection bias accounted for baseline differences between the two groups.

In this study, we detected 15/65 (23%) and 24/136 (18%) local recurrences within 2 yr of surgery in ORC and RARC patients, respectively. In agreement with ORC series, patients who developed local recurrence in the current study usually did so within the first 18 mo after surgery [19], [20], and [21]. Nevertheless, the relatively small number of patients does not preclude the possibility of differences between the two surgical techniques with regard to local recurrence. Importantly, selection bias was present, as patients undergoing ORC presented with higher clinical and pathologic stages.

The most interesting finding with regard to metastases is the distribution of distant recurrence locations between ORC and RARC. The most frequent locations remained the lungs, liver, and bone, which is consistent with the pattern of metastasis seen in autopsy studies and previous clinical series [21], [22], [23], and [24]. However, extrapelvic lymph node locations were more frequent for RARC than for ORC in patients with distant recurrence (10/43 [23%] vs 4/26 [15%]). It is often suggested that the maneuverability of the robotic system may limit the ability to perform a thorough extended PLND. However, we believe that our robot-assisted PLND technique adheres to the same oncologic standards and anatomic boundaries as our open technique. In this study, the median number of lymph nodes removed did not significantly differ between ORC and RARC (20 vs 21). Of course, it is still possible that factors related to the dissection technique are responsible for the current findings. Nevertheless, all of the extrapelvic lymph node recurrences were, by definition, outside the primary extended PLND template, regardless of whether an open or robotic approach was used. One possible explanation for the higher number of extrapelvic lymph node recurrences could be variant lymphatic dissemination as a result of the robotic technique. The true answer to this is not known, however, and the results remain intriguing.

Similarly, peritoneal carcinomatosis was more frequent in RARC patients than in ORC patients with distant recurrence (9/43 [21%] vs 2/26 [8%]). Laparoscopic surgery has been associated with a minimal risk of peritoneal tumor spread through the effect of pneumoperitoneum [10] and [11]. Peritoneal carcinomatosis is found in 16–19% of BCa subjects in autopsy and clinical studies, albeit most often in association with extensive metastases at other locations [22] and [23], while peritoneal carcinomatosis was the sole location in more than half of our cases. However, eight of nine RARC patients who developed peritoneal carcinomatosis had pathologic stage ≥T3, supporting the notion that peritoneal carcinomatosis was more a reflection of cancer biology than a surgical issue. Although the numbers are too few for robust conclusions, our findings warrant further investigations. If differences in recurrence patterns indeed exist between RARC and ORC, we do not believe that the cause is related to the experience level of the surgeon, as most RARC patients with extrapelvic lymph node metastasis or peritoneal carcinomatosis were operated on from 2008 to 2012. Furthermore, precautionary measures are taken to prevent spillage of any malignant cells into the operative field. Following division of the anterior urethral wall, the Foley catheter is immediately clipped with a large Hem-o-lok clip and then cut distal to the clip to maintain the integrity of the balloon. The posterior urethral wall is divided, and the bladder and the indwelling Foley catheter are immediately placed in an Endo Catch bag, thus avoiding urinary extravasation or tumor spillage, which were never observed in this cohort.

Of note, within 2 yr of surgery no secondary urothelial carcinoma was detected in the ORC group, while only four cases were diagnosed in the RARC group. Previous reports have demonstrated that the median time to secondary urothelial carcinomas ranges from 3.3 to 4.3 yr [25] and [26], and rates of urinary tract recurrences are as low as 1.7% at 5 yr [19] . In accordance with our study design, we reported events within 2 yr of surgery. Moreover, the ORC group represented a smaller patient sample than the RARC group. These factors likely explain our findings.

Previous reports evaluating RARC included patients with few comorbidities and low disease burden [14], [27], and [28], which reflects the expected selection bias when a new surgical technique is introduced. Although in our experience these factors have become less important when discussing the surgical technique, selection bias certainly remains, and must be accounted for when drawing conclusions related to oncologic outcomes. The open approach remains the technique of choice in patients with larger tumors and unfavorable local tumor status, allowing easier intraoperative manipulation of specimens [29] . Although adjustment for baseline differences showed no evidence of an additional risk of recurrence in RARC patients, it should be kept in mind that multivariable analyses cannot account for all confounding factors in a data set. Moreover, the CI of the hazard ratio for recurrence is relatively wide, implying that an association between RARC and recurrence cannot be excluded with certainty. However, the fact that extrapelvic lymph node locations and peritoneal carcinomatosis were found more frequently in RARC patients, the cohort with less advanced disease, suggests that selection bias could also have attenuated differences. Potential variations in the use of perioperative chemotherapy are an additional limitation of the study. Taken together, our results are hypothesis-generating and should encourage discussions among urologists.

Open radical cystectomy (ORC) is the mainstay of therapy for patients with muscle-invasive and high-risk non–muscle-invasive bladder cancer (BCa) [1] . Following successful adoption of minimally invasive techniques in kidney and prostate surgery, the last few years have seen growing interest in robot-assisted radical cystectomy (RARC). In retrospective studies [2] and [3] and in the Memorial Sloan Kettering Cancer Center randomized trial [4] , large differences in complication rates between RARC and ORC have not been observed.

However, the introduction of RARC into surgical practice has been accompanied by legitimate concerns regarding its oncologic efficacy [5] . To date, favorable outcomes in terms of positive surgical margin (PSM) rates and lymph node yield have been published [2], [3], and [6]. Early oncologic outcomes appear to be acceptable [7], [8], and [9]. Nevertheless, the use of RARC remains controversial and restricted to specialized centers [3], [6], [7], and [9]. Furthermore, there is anecdotal evidence of peritoneal seeding during minimally invasive surgery [10] , and pneumoperitoneum may impact BCa cell seeding [11] .

In light of the possibility of unusual recurrence locations after RARC, limited information is available for the robotic approach with regard to patterns of disease recurrence. In the present study we describe recurrence patterns in patients who underwent ORC and RARC.

Oncologic efficacy remains the standard that will ultimately verify the true value of RARC. Concerns about proper oncologic resection and the possibility that pneumoperitoneum enhances tumor cell dissemination prompted our precise analysis of recurrence patterns after ORC and RARC, while bearing in mind that selection bias accounted for baseline differences between the two groups.

In this study, we detected 15/65 (23%) and 24/136 (18%) local recurrences within 2 yr of surgery in ORC and RARC patients, respectively. In agreement with ORC series, patients who developed local recurrence in the current study usually did so within the first 18 mo after surgery [19], [20], and [21]. Nevertheless, the relatively small number of patients does not preclude the possibility of differences between the two surgical techniques with regard to local recurrence. Importantly, selection bias was present, as patients undergoing ORC presented with higher clinical and pathologic stages.

The most interesting finding with regard to metastases is the distribution of distant recurrence locations between ORC and RARC. The most frequent locations remained the lungs, liver, and bone, which is consistent with the pattern of metastasis seen in autopsy studies and previous clinical series [21], [22], [23], and [24]. However, extrapelvic lymph node locations were more frequent for RARC than for ORC in patients with distant recurrence (10/43 [23%] vs 4/26 [15%]). It is often suggested that the maneuverability of the robotic system may limit the ability to perform a thorough extended PLND. However, we believe that our robot-assisted PLND technique adheres to the same oncologic standards and anatomic boundaries as our open technique. In this study, the median number of lymph nodes removed did not significantly differ between ORC and RARC (20 vs 21). Of course, it is still possible that factors related to the dissection technique are responsible for the current findings. Nevertheless, all of the extrapelvic lymph node recurrences were, by definition, outside the primary extended PLND template, regardless of whether an open or robotic approach was used. One possible explanation for the higher number of extrapelvic lymph node recurrences could be variant lymphatic dissemination as a result of the robotic technique. The true answer to this is not known, however, and the results remain intriguing.

Similarly, peritoneal carcinomatosis was more frequent in RARC patients than in ORC patients with distant recurrence (9/43 [21%] vs 2/26 [8%]). Laparoscopic surgery has been associated with a minimal risk of peritoneal tumor spread through the effect of pneumoperitoneum [10] and [11]. Peritoneal carcinomatosis is found in 16–19% of BCa subjects in autopsy and clinical studies, albeit most often in association with extensive metastases at other locations [22] and [23], while peritoneal carcinomatosis was the sole location in more than half of our cases. However, eight of nine RARC patients who developed peritoneal carcinomatosis had pathologic stage ≥T3, supporting the notion that peritoneal carcinomatosis was more a reflection of cancer biology than a surgical issue. Although the numbers are too few for robust conclusions, our findings warrant further investigations. If differences in recurrence patterns indeed exist between RARC and ORC, we do not believe that the cause is related to the experience level of the surgeon, as most RARC patients with extrapelvic lymph node metastasis or peritoneal carcinomatosis were operated on from 2008 to 2012. Furthermore, precautionary measures are taken to prevent spillage of any malignant cells into the operative field. Following division of the anterior urethral wall, the Foley catheter is immediately clipped with a large Hem-o-lok clip and then cut distal to the clip to maintain the integrity of the balloon. The posterior urethral wall is divided, and the bladder and the indwelling Foley catheter are immediately placed in an Endo Catch bag, thus avoiding urinary extravasation or tumor spillage, which were never observed in this cohort.

Of note, within 2 yr of surgery no secondary urothelial carcinoma was detected in the ORC group, while only four cases were diagnosed in the RARC group. Previous reports have demonstrated that the median time to secondary urothelial carcinomas ranges from 3.3 to 4.3 yr [25] and [26], and rates of urinary tract recurrences are as low as 1.7% at 5 yr [19] . In accordance with our study design, we reported events within 2 yr of surgery. Moreover, the ORC group represented a smaller patient sample than the RARC group. These factors likely explain our findings.

Previous reports evaluating RARC included patients with few comorbidities and low disease burden [14], [27], and [28], which reflects the expected selection bias when a new surgical technique is introduced. Although in our experience these factors have become less important when discussing the surgical technique, selection bias certainly remains, and must be accounted for when drawing conclusions related to oncologic outcomes. The open approach remains the technique of choice in patients with larger tumors and unfavorable local tumor status, allowing easier intraoperative manipulation of specimens [29] . Although adjustment for baseline differences showed no evidence of an additional risk of recurrence in RARC patients, it should be kept in mind that multivariable analyses cannot account for all confounding factors in a data set. Moreover, the CI of the hazard ratio for recurrence is relatively wide, implying that an association between RARC and recurrence cannot be excluded with certainty. However, the fact that extrapelvic lymph node locations and peritoneal carcinomatosis were found more frequently in RARC patients, the cohort with less advanced disease, suggests that selection bias could also have attenuated differences. Potential variations in the use of perioperative chemotherapy are an additional limitation of the study. Taken together, our results are hypothesis-generating and should encourage discussions among urologists.

Open radical cystectomy (ORC) is the mainstay of therapy for patients with muscle-invasive and high-risk non–muscle-invasive bladder cancer (BCa) [1] . Following successful adoption of minimally invasive techniques in kidney and prostate surgery, the last few years have seen growing interest in robot-assisted radical cystectomy (RARC). In retrospective studies [2] and [3] and in the Memorial Sloan Kettering Cancer Center randomized trial [4] , large differences in complication rates between RARC and ORC have not been observed.

However, the introduction of RARC into surgical practice has been accompanied by legitimate concerns regarding its oncologic efficacy [5] . To date, favorable outcomes in terms of positive surgical margin (PSM) rates and lymph node yield have been published [2], [3], and [6]. Early oncologic outcomes appear to be acceptable [7], [8], and [9]. Nevertheless, the use of RARC remains controversial and restricted to specialized centers [3], [6], [7], and [9]. Furthermore, there is anecdotal evidence of peritoneal seeding during minimally invasive surgery [10] , and pneumoperitoneum may impact BCa cell seeding [11] .

In light of the possibility of unusual recurrence locations after RARC, limited information is available for the robotic approach with regard to patterns of disease recurrence. In the present study we describe recurrence patterns in patients who underwent ORC and RARC.

Oncologic efficacy remains the standard that will ultimately verify the true value of RARC. Concerns about proper oncologic resection and the possibility that pneumoperitoneum enhances tumor cell dissemination prompted our precise analysis of recurrence patterns after ORC and RARC, while bearing in mind that selection bias accounted for baseline differences between the two groups.

In this study, we detected 15/65 (23%) and 24/136 (18%) local recurrences within 2 yr of surgery in ORC and RARC patients, respectively. In agreement with ORC series, patients who developed local recurrence in the current study usually did so within the first 18 mo after surgery [19], [20], and [21]. Nevertheless, the relatively small number of patients does not preclude the possibility of differences between the two surgical techniques with regard to local recurrence. Importantly, selection bias was present, as patients undergoing ORC presented with higher clinical and pathologic stages.

The most interesting finding with regard to metastases is the distribution of distant recurrence locations between ORC and RARC. The most frequent locations remained the lungs, liver, and bone, which is consistent with the pattern of metastasis seen in autopsy studies and previous clinical series [21], [22], [23], and [24]. However, extrapelvic lymph node locations were more frequent for RARC than for ORC in patients with distant recurrence (10/43 [23%] vs 4/26 [15%]). It is often suggested that the maneuverability of the robotic system may limit the ability to perform a thorough extended PLND. However, we believe that our robot-assisted PLND technique adheres to the same oncologic standards and anatomic boundaries as our open technique. In this study, the median number of lymph nodes removed did not significantly differ between ORC and RARC (20 vs 21). Of course, it is still possible that factors related to the dissection technique are responsible for the current findings. Nevertheless, all of the extrapelvic lymph node recurrences were, by definition, outside the primary extended PLND template, regardless of whether an open or robotic approach was used. One possible explanation for the higher number of extrapelvic lymph node recurrences could be variant lymphatic dissemination as a result of the robotic technique. The true answer to this is not known, however, and the results remain intriguing.

Similarly, peritoneal carcinomatosis was more frequent in RARC patients than in ORC patients with distant recurrence (9/43 [21%] vs 2/26 [8%]). Laparoscopic surgery has been associated with a minimal risk of peritoneal tumor spread through the effect of pneumoperitoneum [10] and [11]. Peritoneal carcinomatosis is found in 16–19% of BCa subjects in autopsy and clinical studies, albeit most often in association with extensive metastases at other locations [22] and [23], while peritoneal carcinomatosis was the sole location in more than half of our cases. However, eight of nine RARC patients who developed peritoneal carcinomatosis had pathologic stage ≥T3, supporting the notion that peritoneal carcinomatosis was more a reflection of cancer biology than a surgical issue. Although the numbers are too few for robust conclusions, our findings warrant further investigations. If differences in recurrence patterns indeed exist between RARC and ORC, we do not believe that the cause is related to the experience level of the surgeon, as most RARC patients with extrapelvic lymph node metastasis or peritoneal carcinomatosis were operated on from 2008 to 2012. Furthermore, precautionary measures are taken to prevent spillage of any malignant cells into the operative field. Following division of the anterior urethral wall, the Foley catheter is immediately clipped with a large Hem-o-lok clip and then cut distal to the clip to maintain the integrity of the balloon. The posterior urethral wall is divided, and the bladder and the indwelling Foley catheter are immediately placed in an Endo Catch bag, thus avoiding urinary extravasation or tumor spillage, which were never observed in this cohort.

Of note, within 2 yr of surgery no secondary urothelial carcinoma was detected in the ORC group, while only four cases were diagnosed in the RARC group. Previous reports have demonstrated that the median time to secondary urothelial carcinomas ranges from 3.3 to 4.3 yr [25] and [26], and rates of urinary tract recurrences are as low as 1.7% at 5 yr [19] . In accordance with our study design, we reported events within 2 yr of surgery. Moreover, the ORC group represented a smaller patient sample than the RARC group. These factors likely explain our findings.

Previous reports evaluating RARC included patients with few comorbidities and low disease burden [14], [27], and [28], which reflects the expected selection bias when a new surgical technique is introduced. Although in our experience these factors have become less important when discussing the surgical technique, selection bias certainly remains, and must be accounted for when drawing conclusions related to oncologic outcomes. The open approach remains the technique of choice in patients with larger tumors and unfavorable local tumor status, allowing easier intraoperative manipulation of specimens [29] . Although adjustment for baseline differences showed no evidence of an additional risk of recurrence in RARC patients, it should be kept in mind that multivariable analyses cannot account for all confounding factors in a data set. Moreover, the CI of the hazard ratio for recurrence is relatively wide, implying that an association between RARC and recurrence cannot be excluded with certainty. However, the fact that extrapelvic lymph node locations and peritoneal carcinomatosis were found more frequently in RARC patients, the cohort with less advanced disease, suggests that selection bias could also have attenuated differences. Potential variations in the use of perioperative chemotherapy are an additional limitation of the study. Taken together, our results are hypothesis-generating and should encourage discussions among urologists.