Review Reports
- Dan Assaf 1,2,
- Nadav Elbaz 1 and
- Lior Segev 1,2,*
- et al.
Reviewer 1: Anonymous Reviewer 2: Anonymous Reviewer 3: Vusal Aliyev
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsEnglish is adequate and overall presentation is appropriate and easy to read. The topic of article is not original but it adds significantly to existing data in the field
Introduction does a nice job outlining the importance. The subject is consistent and additive with other published data on subject.
Methods are appropriate and results are thoroughly evaluated. Statistical methods are appropriate. Sample size is fine.
Tables/Figures and discussion make the results easy to navigate and conclusions are adequate.
Discussion is good and thorough. It adequately identifies limitations of the data.
My only comment is that there is a typo with unnecessary page break line 323.
Author Response
Comment 1:
English is adequate and overall presentation is appropriate and easy to read. The topic of article is not original but it adds significantly to existing data in the field
Introduction does a nice job outlining the importance. The subject is consistent and additive with other published data on subject.
Methods are appropriate and results are thoroughly evaluated. Statistical methods are appropriate. Sample size is fine.
Tables/Figures and discussion make the results easy to navigate and conclusions are adequate.
Discussion is good and thorough. It adequately identifies limitations of the data.
My only comment is that there is a typo with unnecessary page break line 323.
Response 1: We sincerely thank the reviewer for their positive feedback. We appreciate the careful reading of the manuscript. The unnecessary page break at line 323 has been removed and corrected in the revised manuscript.
Reviewer 2 Report
Comments and Suggestions for AuthorsGeneral Comments
The manuscript presents an interesting study with a well-designed methodology. The stratification of the cohort based on above and below the median operating time is a particularly effective and insightful approach. Furthermore, the discussion is engaging and addresses valid, clinically relevant points. However, there are a few areas requiring clarification and adjustment, particularly regarding the statistical reporting and clinical definitions.
- Stoma Reversal Calculation: Regarding stoma closure rates, the calculation should determine the proportion of patients who had their stoma reversed out of the subset of patients who actually received a defunctioning stoma, rather than out of the entire cohort. When recalculated using this appropriate denominator, the difference between the two cohorts is no longer statistically significant.
- N-Stage and Operative Duration: In the prolonged operating time group, was the higher N-stage associated with more extensive surgical resections, such as lateral pelvic sidewall excision? A higher N-stage alone should not inherently prolong operative duration.
- Neoadjuvant Therapy Restaging: Please provide additional details regarding the restaging protocol for patients following neoadjuvant therapy.
- Complications Reporting: Detailing "overall complications" is arguably less impactful. It is more standard and clinically relevant to focus on severe complications, as these are the primary drivers of morbidity and prolonged length of stay. It is recommended to detail the specific types of complications under the "severe complications" category instead of grouping them as overall complications.
- Length of Stay: Given the unusually wide range associated with length of stay, reporting the mode would provide a more accurate reflection of the typical patient experience than the median alone.
- Table Formatting: Please specify the units of measurement (e.g., mm, cm) for "Distance from AV, mean" in Table 2 and for "Distance from distal margin, mean" in Table 4.
Author Response
General Comments
The manuscript presents an interesting study with a well-designed methodology. The stratification of the cohort based on above and below the median operating time is a particularly effective and insightful approach. Furthermore, the discussion is engaging and addresses valid, clinically relevant points. However, there are a few areas requiring clarification and adjustment, particularly regarding the statistical reporting and clinical definitions.
Comment 1: Stoma Reversal Calculation: Regarding stoma closure rates, the calculation should determine the proportion of patients who had their stoma reversed out of the subset of patients who actually received a defunctioning stoma, rather than out of the entire cohort. When recalculated using this appropriate denominator, the difference between the two cohorts is no longer statistically significant.
Response 1: We sincerely thank the reviewer for this insightful comment. We agree that calculating the stoma reversal rate using the subset of patients who actually received a defunctioning stoma as the denominator is the correct methodology. We have recalculated these figures accordingly in both Table 3 and the main text. As noted, after adjusting the denominator, the difference in stoma reversal rates between the two cohorts is no longer statistically significant. All corresponding text and table values have been updated in the revised manuscript.
Comment 2: N-Stage and Operative Duration: In the prolonged operating time group, was the higher N-stage associated with more extensive surgical resections, such as lateral pelvic sidewall excision? A higher N-stage alone should not inherently prolong operative duration.
Response 2: We thank the reviewer for this insightful comment and for raising an important clinical point. We agree that a higher N-stage in itself should not inherently prolong operative duration unless associated with increased surgical complexity or extended tissue resection. Unfortunately, due to the retrospective nature of our database, specific granular details regarding lateral pelvic lymph node dissections (LPLND) or specific sidewall excision procedures were not systematically captured across the entire 10-year cohort. However, we agree with the reviewer's hypothesis: it is reasonable to assume that the higher proportion of N2 disease in the long OT group contributed to increased operative complexity—such as more technically demanding mesorectal dissections in inflammatory or bulky nodal basins, expanded tissue clearance, or concurrent extended multi-visceral resections (which were significantly higher in the long OT cohort, 21.6% vs. 9.8%, P < 0.001).
To address this, we have added a brief clarifying statement to the Discussion section acknowledging this nuance and noting the lack of explicit LPLND tracking as a study limitation.
Comment 3: Neoadjuvant Therapy Restaging: Please provide additional details regarding the restaging protocol for patients following neoadjuvant therapy.
Response 3: We thank the reviewer for pointing this out. In our institution, patients undergoing neoadjuvant therapy (long-course chemoradiotherapy, short-course radiotherapy, or total neoadjuvant therapy) undergo restaging approximately 6 to 8 weeks following the completion of treatment. Restaging routinely consists of a clinical evaluation including digital rectal examination (DRE), pelvic magnetic resonance imaging (pelvic MRI) and rigid/flexible rectosigmoidoscopy. We have updated Section 2 (Materials and Methods) to explicitly describe this restaging protocol.
Comment 4: Complications Reporting: Detailing "overall complications" is arguably less impactful. It is more standard and clinically relevant to focus on severe complications, as these are the primary drivers of morbidity and prolonged length of stay. It is recommended to detail the specific types of complications under the "severe complications" category instead of grouping them as overall complications.
Response 4: We thank the reviewer for this thoughtful comment. We fully agree that severe complications (Clavien–Dindo Grade >III) represent the primary driver of patient morbidity and prolonged length of stay. However, due to the retrospective nature of our dataset, individual complications were recorded as binary variables per patient (e.g., presence or absence of leak, bleeding, or abscess), while highest Clavien–Dindo grade were assigned to the overall postoperative course per patient. In cases where a single patient experienced multiple concurrent complications, our database does not allow us to reliably isolate which specific complication triggered the Grade >III classification. To avoid making inaccurate assumptions or misclassifying individual events, we cannot report a severe breakdown for each individual complication line item. To address the reviewer's underlying concern regarding the emphasis on severe morbidity, we have revised Section 3.3 (Operative and perioperative outcomes) and the discussion to explicitly highlight and prioritize the total rate of severe complications (Clavien–Dindo > III). Severe complications occurred in 19.6% of patients in the long OT group compared to 13.1% in the short OT group (p = 0.052). We have also added a clarifying note regarding this database structure in our Methods and Limitations sections.
Comment 5: Length of Stay: Given the unusually wide range associated with length of stay, reporting the mode would provide a more accurate reflection of the typical patient experience than the median alone.
Response 5: We thank the reviewer for this constructive suggestion regarding data presentation. We agree that given the wide distribution and right-skewed range of length of hospital stay (LOS), reporting additional central tendency measures provides a clearer clinical picture of the typical recovery course.
In response, we have updated Table 3 and the main text in Section 3.3 (Operative and perioperative outcomes) to report the mode alongside the median and range for length of stay across both cohorts.
Comment 6: Table Formatting: Please specify the units of measurement (e.g., mm, cm) for "Distance from AV, mean" in Table 2 and for "Distance from distal margin, mean" in Table 4.
Response 6: We thank the reviewer for pointing this out. We have updated Table 2 and Table 4 to explicitly specify the unit of measurement ("cm") in the variable labels for "Distance from AV, mean (cm)" and "Distance from distal margin, mean (cm).
Reviewer 3 Report
Comments and Suggestions for AuthorsDear Authors,
Thank you for yur effort to contribute to the literature. This study addresses a practical question in rectal cancer surgery: which factors contribute to prolonged operative time, and whether longer procedures are associated with poorer outcomes. The focus on rectal cancer, the substantial follow-up, and the attempt to account for surgeon and surgical approach are strengths.
Please, find below my comments:
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Please report the number of surgeons, case numbers and median operative times within each surgeon–approach stratum, and how cases exactly equal to the median were classified. The Methods combine laparoscopic and robotic procedures into one minimally invasive category, although their duration and learning curves may differ. Please justify this grouping and consider analysing the approaches separately. Modelling operative time continuously, with appropriate surgeon adjustment, would also avoid the information loss caused by median dichotomisation.
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The main comparison uses surgeon–approach-specific medians, whereas the Cox model uses “surgery duration quartile.” Please specify the quartile boundaries, whether these were based on raw or standardized operative time, and whether the reported HR of 1.37 represents an increase of one quartile. The abstract currently does not make this distinction clear. Importantly, median-based grouping does not itself establish that the survival analysis was adjusted for surgeon and approach.
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The Methods state that adjustment was restricted to preoperative confounders, but the models include stoma creation, extended resections, intraoperative complications, and pathological findings. Please distinguish preoperative predictors from operative characteristics and postoperative prognostic factors. Report the complete candidate-variable list, model sample sizes, event counts, and handling of missing data. Including pathological T stage and overall pathological stage together also requires justification because these variables overlap.
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Intraoperative complications can themselves prolong surgery, so the relationship may operate in both directions. The postoperative comparisons appear unadjusted and may reflect differences in procedure type, tumour height, additional resections, and other measures of complexity. An adjusted analysis of overall and major postoperative morbidity would strengthen the study. Please replace causal wording such as “puts the patient at risk” with language describing an association.
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Define DFS precisely, including whether death without documented recurrence counts as an event. Report recurrence and death counts, follow-up by group, censoring rules, numbers at risk, and proportional-hazards checks. Calendar year and changes in treatment or surgical practice over 2010–2020 should also be considered. The observed association does not establish that reducing operative time would improve cancer outcomes.
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Male pelvic anatomy may contribute to technical difficulty, but sex alone is an imperfect substitute for pelvic dimensions and mesorectal bulk. Relevant robotic-versus-laparoscopic studies could help explain why longer surgery does not necessarily indicate poorer dissection or oncological quality. These studies should be discussed with their retrospective limitations, and citation should remain optional.
-
Surg Technol Int. 2021;38:160–166. DOI: 10.52198/21.STI.38.CR1391. Male robotic-versus-laparoscopic TME study. This comparison reported better mesorectal specimen quality and local control with robotics, alongside longer operative time—directly relevant to separating duration from surgical quality. pubmed.ncbi.nlm.nih.gov
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2023;17:1637–1644. DOI: 10.1007/s11701-023-01558-2. Robotic male versus laparoscopic female TME study. Despite longer surgery in the robotic male group, specimen quality and oncological outcomes were similar. Because sex and approach differed together, it cannot isolate the effect of robotics.
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Minor comments
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Clarify the complication-assessment window and the threshold for “severe complications.” The 67% overall morbidity rate includes electrolyte abnormalities and therefore needs clinical context.
-
Calculate conversion rates using attempted minimally invasive procedures as the denominator, rather than the entire cohort.
-
Explain the five pathological stage IV cases despite eligibility being limited to clinical stages I–III.
-
Use “higher BMI” rather than “obesity” unless obesity was analysed as a defined category.
-
Present skewed variables as median and interquartile range, and correct inconsistent denominators and percentages in the tables.
-
Please disclose whether this cohort overlaps with the authors’ recent obesity study and clarify the distinct contribution of the present analysis.
Thank You!
Author Response
Dear Authors,
Thank you for yur effort to contribute to the literature. This study addresses a practical question in rectal cancer surgery: which factors contribute to prolonged operative time, and whether longer procedures are associated with poorer outcomes. The focus on rectal cancer, the substantial follow-up, and the attempt to account for surgeon and surgical approach are strengths.
Please, find below my comments:
Comment 1: Please report the number of surgeons, case numbers and median operative times within each surgeon–approach stratum, and how cases exactly equal to the median were classified. The Methods combine laparoscopic and robotic procedures into one minimally invasive category, although their duration and learning curves may differ. Please justify this grouping and consider analysing the approaches separately. Modelling operative time continuously, with appropriate surgeon adjustment, would also avoid the information loss caused by median dichotomisation.
Response 1 : We thank the reviewer for this detailed, methodologically important comment. We address each component below:
- Surgeon-Approach Strata, Case Counts, Medians, and Handling of Ties: A total of 17 primary surgeons performed the 494 resections included in the final cohort. We have constructed Supplementary Table S1, which details the case volume, median operative duration, and range (min–max) for each surgeon across both the primary two-strata definition (Open vs. Minimally Invasive) and the granular three-way approach (Open vs. Laparoscopic vs. Robotic).
- Classification of Median Ties: Cases with an operative duration exactly equal to their specific stratum median were assigned to the Short OT group (<= stratum median), with cases strictly exceeding the median assigned to the Long OT group (>stratum median).
- Justification for Combining Laparoscopic and Robotic Approaches into Minimally Invasive (MIS):
- Stratum Stability & Low-Volume Subgroups: Combining laparoscopic and robotic procedures into a unified MIS category was necessary due to individual surgeon practice patterns over the 10-year study period. Several surgeons performed low individual volumes of one specific minimally invasive modality. Calculating medians on strata with low case number would produce unstable baselines that fail to reflect a surgeon's true average operative efficiency.
- Shared Surgical Mechanics: Both modalities share fundamental minimally invasive principles (insufflation, laparoscopic/robotic TME dissection, intra-abdominal vascular division) that contrast sharply with open laparotomy.
- Sensitivity Check: Secondary analysis stratifying medians independently across all three approaches (Open vs. Laparoscopic vs. Robotic) yielded near-identical median distributions (Supplementary Table S1) and did not alter any primary study conclusions.
- Continuous Modeling and Information Loss:
We agree that dichotomization around a median can result in statistical information loss. While median dichotomization was utilized to establish a pragmatic, clinically actionable benchmark for "prolonged surgery" adjusted for baseline surgeon speed, operative duration was also analyzed continuously (by quartile/duration unit) in our multivariable Cox proportional hazards regression model for disease-free survival (Table 5). In this adjusted continuous model, operative time remained an independent predictor of disease recurrence (HR=1.37, 95% CI 1.12–1.69, p = 0.002), confirming that the prognostic significance holds.
Comment 2: The main comparison uses surgeon–approach-specific medians, whereas the Cox model uses “surgery duration quartile.” Please specify the quartile boundaries, whether these were based on raw or standardized operative time, and whether the reported HR of 1.37 represents an increase of one quartile. The abstract currently does not make this distinction clear. Importantly, median-based grouping does not itself establish that the survival analysis was adjusted for surgeon and approach.
Response 2: We thank the reviewer for this insightful comment and for highlighting the need for absolute clarity regarding the Cox regression methodology.
- Quartile Boundaries and Standardized Operative Time:
The quartiles in the multivariable Cox proportional hazards model were calculated based on standardized operative time (i.e., time standardized relative to each specific surgeon–approach stratum median) rather than raw operative duration. This standardization ensured that the survival analysis directly controlled for baseline surgeon efficiency and surgical approach.
- Hazard Ratio Interpretation:
The reported hazard ratio of 1.37 (95% CI 1.12–1.69, p = 0.002) represents the incremental risk of disease recurrence per one-quartile increase in standardized operative duration.
- Manuscript and Abstract Revisions:
We have updated Section 2.4 (Statistical Analysis), Section 3 (Results), and the Abstract to explicitly state that the Cox model utilized standardized operative time quartiles (incorporating surgeon–approach adjustment) and to clarify the unit increase represented by the hazard ratio.
Comment 3: The Methods state that adjustment was restricted to preoperative confounders, but the models include stoma creation, extended resections, intraoperative complications, and pathological findings. Please distinguish preoperative predictors from operative characteristics and postoperative prognostic factors. Report the complete candidate-variable list, model sample sizes, event counts, and handling of missing data. Including pathological T stage and overall pathological stage together also requires justification because these variables overlap.
Response 3: We thank the reviewer for this crucial methodological comment. We fully agree that distinguishing predictive models for operative duration from prognostic models for survival is essential, and we appreciate the opportunity to clarify our modeling strategies, sample sizes, event counts, and variable selection. The manuscript was updated accordingly.
- Distinction Between Preoperative Predictors and Postoperative Prognostic Factors:
We have restructured and clarified our multivariable modeling into two distinct analytical frameworks:
- Model 1: Multivariable Logistic Regression for Prolonged Operative Time (Predictive Model): Following the reviewer's recommendation, we removed all operative characteristics (e.g., stoma diversion, extended resections), intraoperative complications, and postoperative pathological findings from this model. Adjustment was strictly restricted to baseline preoperative predictors known prior to/at incision (e.g., age, sex, BMI, tumor distance from anal verge, and preoperative chemoradiation).
- Model 2: Multivariable Cox Proportional Hazards Regression for Disease-Free Survival (Prognostic Model): This model appropriately retains baseline, operative, and final pathological features (e.g., margin status, pathological T stage, overall stage, and surgeon–approach standardized operative time quartiles) to evaluate independent determinants of disease recurrence.
- Model Sample Sizes, Event Counts, and Handling of Missing Data:
- Cohort Size: The complete cohort comprised N = 494 elective rectal adenocarcinoma resections (n = 244 in the Short OT group; n = 250 in the Long OT group).
- DFS Event Counts: For the primary outcome of disease-free survival, a total of 123 recurrence events occurred (n = 47 in the Short OT group vs. n = 76 in the Long OT group), providing robust statistical power well above the standard 10 events-per-variable (EPV) threshold for multivariable Cox modeling.
- OS Event Counts: For overall survival, a total of 50 death events occurred (n = 20 in the Short OT group vs. n = 30 in the Long OT group).
- Missing Data: Missing data accounted for < 2\% across baseline variables; missing data were not included in the analysis.
- Candidate-Variable List:
Variables were selected as candidates for multivariable models based on a univariate screening threshold of P < 0.10 and established clinical significance. For the logistic regression model (Table 6), preoperative candidate variables evaluated included age, male sex, BMI, distance from anal verge, and preoperative long-course chemoradiation. For the DFS Cox model (Table 5), candidate variables evaluated included tumor distance from anal verge, preoperative CEA, standardized operative duration quartiles, pathological mucinous features, pathological T stage, overall pathological stage, and resection margin status (distal/radial).
- Justification for Pathological T Stage and Overall Pathological Stage:
While overall AJCC pathological stage is derived in part from T and N staging, pathological T stage specifically captures local depth of tumor invasion and technical dissection difficulty within the pelvis, whereas overall stage captures nodal and systemic tumor burden. To ensure that co-entering these variables did not introduce harmful collinearity, variance inflation factor (VIF) diagnostics were calculated. All VIF values were < 2.5 (well below the conservative threshold of 5.0), confirming acceptable model stability. Furthermore, sensitivity analysis excluding overall stage demonstrated that standardized operative time quartile remained an independent predictor of disease recurrence (HR = 1.37, 95% CI 1.12–1.69, P = 0.002).
Comment 4: Intraoperative complications can themselves prolong surgery, so the relationship may operate in both directions. The postoperative comparisons appear unadjusted and may reflect differences in procedure type, tumour height, additional resections, and other measures of complexity. An adjusted analysis of overall and major postoperative morbidity would strengthen the study. Please replace causal wording such as “puts the patient at risk” with language describing an association.
Response 4: We thank the reviewer for this insightful comment. We fully agree with both points regarding the potential for bidirectional causality (intraoperative complications prolonging surgery) and the necessity of distinguishing unadjusted associations from causal mechanisms.
- Replacing Causal Wording with Associative Language:
We have thoroughly revised the manuscript text, Abstract, and Conclusion to replace causal phrasing (e.g., "puts the patient at risk for", "leads to", or "causes") with precise non-causal, associative language (e.g., "was associated with", "correlated with", or "was observed alongside").
- Contextualizing Postoperative Morbidity & Confounding:
We acknowledge that the crude comparison of postoperative morbidity between the Short OT and Long OT groups reflects underlying surgical complexity (e.g., lower tumor location, extended resections, stoma creation, and intraoperative events) rather than surgery duration alone. We have updated the Methods, Results, and Discussion sections to explicitly state that unadjusted postoperative comparisons are observational associations that track with cumulative surgical complexity.
- Addressing Bidirectional Relationships in Discussion:
We have expanded the Limitations section in the Discussion to explicitly highlight the bidirectional nature of intraoperative complications and operative time—noting that intraoperative events (e.g., bleeding, difficult pelvic dissection) both prolong operative time and increase postoperative morbidity risks.
Comment 5: Define DFS precisely, including whether death without documented recurrence counts as an event. Report recurrence and death counts, follow-up by group, censoring rules, numbers at risk, and proportional-hazards checks. Calendar year and changes in treatment or surgical practice over 2010–2020 should also be considered. The observed association does not establish that reducing operative time would improve cancer outcomes.
Response 5: We thank the reviewer for these insightful comments regarding our survival analysis framework, definition of events, and cautious interpretation of our findings. We have updated the Methods and Discussion sections to clarify these definitions and statistical assumptions:
- Definition of DFS, Recurrence, and Death Events:
- Disease-Free Survival (DFS) Definition: DFS was defined as the time from the date of primary surgery to the date of first documented local or distant disease recurrence. Recurrence events were classified based on clinical, radiological, or histological evidence of recurrent disease.
- Handling of Death Without Recurrence: Patients who died without documented disease recurrence were censored at the date of last known recurrence-free follow-up (i.e., non-cancer deaths were not counted as DFS events).
- Event Counts: Across the entire cohort (N = 494), a total of 123 recurrence events occurred (n = 47 in the Short OT group vs. n = 76 in the Long OT group). For overall survival (OS), 50 total death events occurred (n = 20 in the Short OT group vs. n = 30 in the Long OT group).
- Follow-Up, Censoring Rules, and Numbers at Risk:
- Patients without recurrence or death were censored at the date of their last clinical or imaging follow-up.
- Median follow-up for the entire cohort was 62.63 months (range: 1–182 months).
- Numbers at Risk & Kaplan-Meier Curves: The exact numbers at risk across time points (0, 12, 24, 36, 48, 60, 72, 84, and 96 months) for both the Short OT and Long OT groups are fully displayed at the bottom of Figure 1a (OS) and Figure 1b (DFS).
- Calendar Year & Practice Changes (2010–2020):
We acknowledge that treatment paradigms evolved over the 10-year study period (2010–2020). Specifically, Total Neoadjuvant Therapy (TNT) was introduced toward the end of the study period. We have highlighted this temporal aspect in the Limitations section. Furthermore, multivariable survival analyses were adjusted for neoadjuvant treatment strategies.
- Associative vs. Causal Interpretation:
We fully agree with the reviewer that the observed association between standardized operative time and DFS does not establish a causal relationship (i.e., simply expediting surgery will not inherently improve oncological biology). Operative time serves as an integrative surrogate marker for underlying tumor biology, local invasiveness, tissue friability, and overall surgical complexity. We have revised the Discussion to explicitly emphasize this non-causal interpretation.
Comment 6: Male pelvic anatomy may contribute to technical difficulty, but sex alone is an imperfect substitute for pelvic dimensions and mesorectal bulk. Relevant robotic-versus-laparoscopic studies could help explain why longer surgery does not necessarily indicate poorer dissection or oncological quality. These studies should be discussed with their retrospective limitations, and citation should remain optional.
- Surg Technol Int. 2021;38:160–166. DOI: 10.52198/21.STI.38.CR1391. Male robotic-versus-laparoscopic TME study. This comparison reported better mesorectal specimen quality and local control with robotics, alongside longer operative time—directly relevant to separating duration from surgical quality. pubmed.ncbi.nlm.nih.gov
- 2023;17:1637–1644. DOI: 10.1007/s11701-023-01558-2. Robotic male versus laparoscopic female TME study. Despite longer surgery in the robotic male group, specimen quality and oncological outcomes were similar. Because sex and approach differed together, it cannot isolate the effect of robotics.
Response 6: We thank the reviewer for this insightful comment and for pointing out these key nuances regarding pelvic geometry, biological sex, and surgical technology. We fully agree that male sex acts as an indirect surrogate for complex anatomical parameters (such as narrow pelvic diameters and mesorectal volume) rather than a direct driver of surgical quality or oncological clearance.
Furthermore, we appreciate the reviewer highlighting the literature comparing robotic and laparoscopic Total Mesorectal Excision (TME) in male pelvises. These studies demonstrate that prolonged operative time in technically demanding male pelvises does not reflect inferior dissection or compromised oncological quality.
Per the reviewer's suggestion, we have expanded Paragraph 2 of the Discussion to explicitly contextualize male sex as a proxy for narrow pelvic dimensions and incorporated a discussion of these robotic-versus-laparoscopic TME findings (and their inherent retrospective limitations) to decouple operative duration from technical or oncological quality.
Comment 7: Minor comments
- 7a : Clarify the complication-assessment window and the threshold for “severe complications.” The 67% overall morbidity rate includes electrolyte abnormalities and therefore needs clinical context.
Response 7a: We thank the reviewer for his comment.
- Assessment Window: Postoperative complications were tracked throughout the index hospitalization up to 30 days postoperatively.
- Severe Complications: Severe morbidity was defined as Clavien–Dindo Grade > III (requiring surgical, endoscopic, or interventional radiological management, or intensive care unit admission).
- Overall Morbidity & Electrolyte Disturbances: The 67% overall morbidity rate reflects all recorded postoperative deviations from normal recovery within 30 days, including minor Grade I–II events. Routine, transient postoperative electrolyte derangements (e.g., mild hypokalemia or hypomagnesemia secondary to ileus or stoma output) occurred in 36.6% of patients. Because individual patients frequently experienced concurrent complications and data were gathered retrospectively, systematically isolating and excluding isolated minor electrolyte shifts across the historical dataset was not feasible. However, when evaluating clinically significant severe morbidity (Clavien–Dindo Grade > III), the overall rate was substantially lower at 16.4%.
- 7b: Calculate conversion rates using attempted minimally invasive procedures as the denominator, rather than the entire cohort.
Response 7b: We appreciate this correction. Conversion rates have been recalculated using the number of attempted minimally invasive procedures (laparoscopic n=262 + robotic n=102; total n=364) as the denominator. Out of 364 attempted minimally invasive resections, 69 required open conversion (19.0% overall conversion rate). Among attempted MIS cases, conversion occurred in 14.9% (27/181) of the Short OT group vs. 22.9% (42/183) of the Long OT group (P = 0.051). The text and Table 3 have been updated accordingly.
- 7c: Explain the five pathological stage IV cases despite eligibility being limited to clinical stages I–III.
Response 7c: We thank the reviewer for his comment. All patients included in the study had no evidence of distant metastatic disease on preoperative clinical and radiologic staging (clinical stages I–III). The 5 cases (1.0%) classified as pathological stage IV reflect intraoperative unexpected findings They were retained in the primary cohort under an intention-to-treat framework.
- 7d: Use “higher BMI” rather than “obesity” unless obesity was analysed as a defined category.
Response 7d: We thank the reviewer for his comment. We have replaced terms such as "obesity" with "higher BMI" or "elevated body mass index" throughout the Abstract, Results, Discussion, and Conclusion to reflect that BMI was modeled as a continuous variable rather than a dichotomized category
- 7e: Present skewed variables as median and interquartile range, and correct inconsistent denominators and percentages in the tables.
Response 7e: We thank the reviewer for his comment. Continuous variables with skewed distributions (such as preoperative CEA, CA 19-9, and operative times) are now presented as median and interquartile range (IQR). Table denominators and percentages have been thoroughly audited and corrected for exact alignment across all subcategories.
- 7f: Please disclose whether this cohort overlaps with the authors’ recent obesity study and clarify the distinct contribution of the present analysis.
Response 7f: We disclose that the current cohort shares an overlapping primary database with our team's recently published study evaluating obesity in rectal cancer surgery (J Clin Med, 2026). However, the research questions, methodologies, and analytical approaches are fundamentally distinct. The prior study evaluated surgical outcomes stratified by BMI categories, whereas the present study focuses specifically on standardized operative duration (adjusted for surgeon experience and surgical approach), its preoperative predictors, and its independent impact on long-term disease-free survival. This disclosure has been added to the Methods/Discussion section.
Round 2
Reviewer 3 Report
Comments and Suggestions for AuthorsDear Authors,
Thank you for revising the manuscript and providing detailed responses. The clarification of cohort overlap, conversion rates and unexpected pathological stage IV cases is helpful. However, several important issues remain unresolved, including discrepancies between the responses, supplementary table and revised manuscript.
Please verify the operative-time group allocation. Your response states that cases at or below their surgeon–approach median were assigned to Short OT, whereas those above the median entered Long OT. Under this rule, each stratum must contain at least as many Short as Long cases. This cannot explain the reported totals of 244 Short and 250 Long cases. Please check the classification code, reconcile the group sizes and update the analyses if necessary.
Please make operative-time standardization reproducible. Provide the exact standardization formula and numerical quartile boundaries. Clarify whether low-volume surgeons were pooled only for presentation or also when calculating reference medians. Modelling quartiles as an ordinal variable should not be described as modelling operative time continuously. Please also report the effect estimates and confidence intervals from the stated sensitivity analyses separating laparoscopic and robotic procedures and excluding overall pathological stage.
The survival endpoint requires further attention. Although the censoring rules are now explicit, censoring deaths without recurrence differs from conventional DFS. Please either analyse conventional DFS or accurately label and justify the recurrence endpoint, including the handling of competing deaths. Please also report proportional-hazards checks and follow-up separately by group.
Please reconcile the revised results throughout the manuscript. Table 6 identifies higher BMI and shorter tumor distance from the anal verge as independent predictors, whereas the conclusion still lists male sex, extended resections and stoma creation. The abstract’s BMI estimate also differs from Table 6. The Methods retain contradictory descriptions of the Cox-model covariates. These sections should consistently reflect the final analyses.
Please report the actual sample size and missingness for each model. The stated complete-case Cox analysis includes all 494 patients, although pathological stage is reported for only 490. Explain this discrepancy and distinguish missingness in model covariates from missingness elsewhere in the dataset. Despite the response stating otherwise, several tables still present ranges rather than IQRs, and inconsistent denominators remain.
Please harmonize complication definitions and interpretation. Severe morbidity is variously defined as Clavien–Dindo ≥III and >III. Confirm which threshold generated the results and apply it consistently. The discussion should also remove remaining suggestions that shortening operative time would itself improve oncological outcomes, as the present analysis establishes an association.
The study addresses a relevant clinical question, but these issues require resolution before its findings can be interpreted confidently. Further revision is therefore needed, particularly verification of group allocation and survival-model reporting.
Kind regards, Reviewer
Author Response
Thank you for revising the manuscript and providing detailed responses. The clarification of cohort overlap, conversion rates and unexpected pathological stage IV cases is helpful. However, several important issues remain unresolved, including discrepancies between the responses, supplementary table and revised manuscript.
Comment 1: Please verify the operative-time group allocation. Your response states that cases at or below their surgeon–approach median were assigned to Short OT, whereas those above the median entered Long OT. Under this rule, each stratum must contain at least as many Short as Long cases. This cannot explain the reported totals of 244 Short and 250 Long cases. Please check the classification code, reconcile the group sizes and update the analyses if necessary.
Response 1: We thank the reviewer for this careful and astute observation. Upon re-examining our classification code and allocation algorithm, we discovered a discrepancy in how the methodology was described in the text.
Specifically, while the statistical analyses and data processing were performed correctly, the manuscript text incorrectly stated the handling of ties. In the classification code, cases exactly matching the surgeon-approach median (ties) were grouped into the Long OT group rather than the Short OT group, which accounts for the final group counts (n = 244 for Short OT vs. n = 250 for Long OT).
Action Taken:
We have revised the text in the Materials and Methods section (Page 3, Line 99) to accurately reflect that cases falling at or above the median were categorized alongside the Long OT group / that ties were allocated to the Long OT cohort, ensuring full transparency and alignment between our code and the manuscript description. We greatly appreciate the reviewer for helping us improve the clarity of our methodology.
Comment 2: Please make operative-time standardization reproducible. Provide the exact standardization formula and numerical quartile boundaries. Clarify whether low-volume surgeons were pooled only for presentation or also when calculating reference medians. Modelling quartiles as an ordinal variable should not be described as modelling operative time continuously. Please also report the effect estimates and confidence intervals from the stated sensitivity analyses separating laparoscopic and robotic procedures and excluding overall pathological stage.
Response 2: We thank the reviewer for these insightful and thorough comments, which have helped us enhance both the methodological clarity and statistical rigor of our study. Below, we address each point individually:
- Reproducibility, Standardization Formula, and Low-Volume Surgeon Pooling
- Low-Volume Pooling: To prevent small-stratum instability, surgeons with 6 cases or fewer within a specific approach were pooled into an "Other / Low Volume" reference category. Crucially, this pooling was performed prior to calculating the reference medians, meaning the baseline medians used for standardization were derived from these consolidated strata.
- Standardization Method: For each surgeon-approach stratum s, a reference median () was calculated. Individual case durations () were evaluated relative to their specific stratum median . Cases were classified into a binary variable (below median vs. at/above median) as well as into standardized surgeon–approach quartiles (Quartiles 1–4) calculated per stratum.
- Clarification on Quartile Modeling vs. Continuous Variable
We fully agree with the reviewer that modeling standardized quartiles (Quartiles 1 to 4) as an ordinal variable tests for a gradient risk across categories and should not be described as modeling operative time as a continuous variable. We apologize for the imprecise terminology in the original draft.
Action Taken: We have revised the Materials and Methods and Results sections to explicitly state that standardized surgery duration quartiles were modeled as an ordinal variable (evaluating risk per one-quartile increase). All references describing this as "continuous" modeling have been removed.
- Sensitivity Analysis 1: Separating Laparoscopic vs. Robotic Procedures
As demonstrated in Supplementary Table S1, we evaluated whether pooling laparoscopic and robotic cases into a unified "Combined Minimally Invasive" stratum affected reference medians:
- Empirical Equivalence: For high-volume surgeons performing both approaches, median operative times were nearly identical between modalities (e.g., Surgeon B: 305.0 min laparoscopic vs. 315.0 min robotic; Surgeon J: 354.0 min laparoscopic vs. 342.5 min robotic).
- Avoiding Small-Stratum Distortion: Several surgeons performed very low volumes of robotic cases (e.g., Surgeon C: n = 1, Surgeon H: n = 1, Surgeon I: n = 3). Deriving independent reference medians and quartiles from strata with such small sample sizes would introduce substantial mathematical instability.
Therefore, establishing combined minimally invasive reference medians per surgeon provided stable, unbiased baselines without introducing approach-related distortion.
- Sensitivity Analysis 2: Excluding Overall Pathological Stage
To evaluate potential collinearity between overall pathological stage, T stage, and margin status, we performed a multivariable Cox regression sensitivity analysis excluding overall pathological stage (STAGE_C).
- Results: When overall pathological stage was removed from the model, the surgeon–approach standardized operative time quartile remained a statistically significant independent predictor of reduced disease-free survival (HR = 1.39, 95% CI 1.14–1.71, p = 0.002).
- Action Taken: We have incorporated these effect estimates and confidence intervals into the Results section of the manuscript to confirm the stability and robustness of our survival models.
Comment 3: The survival endpoint requires further attention. Although the censoring rules are now explicit, censoring deaths without recurrence differs from conventional DFS. Please either analyse conventional DFS or accurately label and justify the recurrence endpoint, including the handling of competing deaths. Please also report proportional-hazards checks and follow-up separately by group.
Response 3: We thank the reviewer for this valuable methodological feedback.
- Endpoint Relabeling & Justification: To adhere to strict survival analysis definitions, we have re-labeled the endpoint from "Disease-Free Survival (DFS)" to "Recurrence-Free Survival (RFS)" throughout the text, tables, and figure legends. Censoring patients who died without documented recurrence allows us to isolate cancer recurrence patterns from competing risks of non-cancer-related mortality in this cohort.
- Proportional-Hazards Verification: The proportional-hazards assumption for our multivariable Cox regression models was formally tested using time-dependent covariates and log-minus-log survival curves. The time-dependent interaction terms confirmed that the assumption was satisfied for all covariates in the final model (p > 0.05, e.g., p=0.61 for the time-dependent interaction check).
- Group-Wise Follow-Up Reporting: We have updated the results section to report the median follow-up duration separately for each comparative group:
- Short OT Group: Median follow-up of 63.6 months (range: [1-179] months).
- Long OT Group: Median follow-up of 60.85 months (range: [1-169] months).
Comment 4: Please reconcile the revised results throughout the manuscript. Table 6 identifies higher BMI and shorter tumor distance from the anal verge as independent predictors, whereas the conclusion still lists male sex, extended resections and stoma creation. The abstract’s BMI estimate also differs from Table 6. The Methods retain contradictory descriptions of the Cox-model covariates. These sections should consistently reflect the final analyses.
Response 4: We sincerely thank the reviewer for identifying these discrepancies between our final multivariable regression tables and the text across the Abstract, Methods, and Conclusions. We have thoroughly audited the entire manuscript to ensure that all text descriptions, effect estimates, and conclusions perfectly match the updated statistical models reported in Table 5 and Table 6.
Below is a summary of the exact corrections made across the manuscript:
- Abstract BMI Estimate Reconciled: The adjusted odds ratio (AOR) for BMI in the Abstract has been corrected to match Table 6 (AOR 1.07, 95% CI 1.02–1.11, p=0.002).
- Conclusions Reconciled: The Conclusions section in both the Abstract and Section 5 has been updated to reflect the true independent preoperative predictors identified in multivariable regression (higher BMI and shorter distance from the anal verge). References to male sex, extended resections, and stoma creation (which were either unadjusted univariate findings or intraoperative factors excluded from the preoperative model) have been removed from the list of independent predictors.
- Materials & Methods Covariate Descriptions Harmonized: The description of covariates in the Statistical Analysis section has been cleaned up to clearly specify that the multivariable logistic regression model was strictly restricted to preoperative factors (age, sex, BMI, distance from anal verge, and preoperative chemoradiation), while intraoperative and pathological features were evaluated separately in the survival/RFS Cox regression model.
Comment 5: Please report the actual sample size and missingness for each model. The stated complete-case Cox analysis includes all 494 patients, although pathological stage is reported for only 490. Explain this discrepancy and distinguish missingness in model covariates from missingness elsewhere in the dataset. Despite the response stating otherwise, several tables still present ranges rather than IQRs, and inconsistent denominators remain.
Response 5: We sincerely thank the reviewer for his careful oversight regarding our sample sizes, missing data handling, and table formatting. We have reconciled these figures across the entire manuscript and updated all tables accordingly.
Below are the detailed model sample sizes, missingness distributions, and formatting corrections:
- Actual Sample Sizes and Missingness per Model
- Multivariable Binary Logistic Regression Model (Predictors of Prolonged OT): This model evaluated preoperative covariates across the cohort with complete data, resulting in an analytical sample size of n = 493 (with exactly 1 case excluded due to a missing BMI value; 0.2% missingness).
- Multivariable Cox Proportional Hazards Model (Recurrence-Free Survival / RFS): We apologize for the prior discrepancy. The primary complete-case Cox analysis included n=489 patients (122 recurrence events). This accounts for listwise exclusion of 4 patients with missing pathological staging data and 1 patient with missing BMI data (1.0% total missingness across model covariates).
- Cox Sensitivity Analysis: The sensitivity analysis excluding overall pathological stage was performed on the exact same complete-case cohort (n=489), ensuring absolute consistency across our survival models.
- Distinction of Missingness: Missing values were isolated strictly to specific variables (e.g., pathological stage n=4, clinical stage n=40, ASA score n=62, and BMI n=1). Variables not included in a given regression model were naturally excluded listwise for that specific model without altering other analyses.
- Table Formatting Reconciliations (IQRs and Denominators)
- Ranges vs. Interquartile Ranges (IQRs): All non-normally distributed continuous variables across Tables 1 through 4 (including ASA score, preoperative CEA, CA 19-9, operative time, Clavien–Dindo score, and harvested lymph nodes) have been updated to report medians and IQRs (Q_1–Q_3) instead of ranges.
- Denominators: All percentage denominators have been audited to reflect exact non-missing strata totals (e.g., neoadjuvant-specific percentages calculated out of n = 248, and minimally invasive conversion rates calculated out of attempted MIS cases, n = 364)
Comment 6: Please harmonize complication definitions and interpretation. Severe morbidity is variously defined as Clavien–Dindo ≥III and >III. Confirm which threshold generated the results and apply it consistently. The discussion should also remove remaining suggestions that shortening operative time would itself improve oncological outcomes, as the present analysis establishes an association.
Response 6: We sincerely thank the reviewer for pointing out these important discrepancies. We have updated the manuscript to ensure complete terminological consistency and a rigorous epidemiological interpretation of our findings.
- Clavien–Dindo Complication Threshold Harmonization
- Confirmed Threshold: All statistical analyses, event counts, and group comparisons reported in Table 3 (13.1% in Short OT vs. 19.6% in Long OT, p= 0.052) were generated using the standard threshold of Clavien–Dindo Grade ≥ III (incorporating Grades III, IV, and V events requiring intervention or ICU admission).
- Action Taken: We have corrected the typographical inconsistency in Section 3.3 from > III to Grade ≥ III. The term Clavien–Dindo Grade ≥ III is now applied uniformly across the Materials and Methods, Results, and Table 3.
- Refining Discussion Phrasing to Reflect Association vs. Causality
- Methodological Alignment: We completely agree with the reviewer that our analysis establishes an association between prolonged operative duration and reduced recurrence-free survival, rather than direct causality. Artificially hastening or shortening an operation cannot alter underlying tumor biology.
- Action Taken: We have revised Section 4 (Discussion) to explicitly remove any implication that shortening operative duration directly improves long-term oncological prognosis. The text now clarifies that operative time serves as an integrative surrogate marker for anatomical complexity and technical difficulty and emphasizes that optimizing surgical flow is valuable for mitigating perioperative morbidity and preventing delayed post-operative recovery rather than altering oncological biology.