Assessing First and Multiple Reoperations in 23,301 Breast Reconstructions: Immediate Versus Delayed Reconstructions in Women with Breast Cancer

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This article addresses an important topic of breast cancer management – the breast reconstruction strategy after mastectomy, to be precise. The authors tackle the long-standing debate of which type of reconstruction is superior (immediate versus delayed).

The American group analyzed a retrospective cohort of 23,301 patients with breast reconstruction after mastectomy for cancer. The article methodology is rigorous. The data was appropriately curate and the statistical tests well employed. The results are clearly and concisely presented, and the discussion section is well designed.

However, some changes should be made in order to improve the quality of the study:

1. In line 30 of the Abstract the is bracket with “(reference)” – this should be delt with
2. The 1^st phrase of the Introduction paragraph should be update (since it refers to last year’s dates) – lines 49-51
3. In line 83 the acronym CPT is used for the 1^st time without it being written in-extenso
4. The headings of all tables should be edited in order to be easier readable

The results of this large study are of an increase interest for the scientific community and may help (after future systematic reviews / meta-analyses will be made) in the decision-making process breast reconstruction strategy after mastectomy for cancer.

Author Response

This article addresses an important topic of breast cancer management – the breast reconstruction strategy after mastectomy, to be precise. The authors tackle the long-standing debate of which type of reconstruction is superior (immediate versus delayed).

The American group analyzed a retrospective cohort of 23,301 patients with breast reconstruction after mastectomy for cancer. The article methodology is rigorous. The data was appropriately curate and the statistical tests well employed. The results are clearly and concisely presented, and the discussion section is well designed.

However, some changes should be made in order to improve the quality of the study:

1. In line 30 of the Abstract the is bracket with “(reference)” – this should be delt with

Author response: Thank you we have corrected the error.

2. The 1^st phrase of the Introduction paragraph should be update (since it refers to last year’s dates) – lines 49-51

Author Response: Thank you very much. We agree and have updated the reference and statistics for the year 2025.

(Lines 49-51): “Breast cancer is the most common cancer in women in the United States, except for non-melanoma skin cancers, and the American Cancer Society projects that 316,950 new cases of invasive breast cancer will be diagnosed in women in the United States in 2025.”

3. In line 83 the acronym CPT is used for the 1^st time without it being written in-extenso

Author Response: Thank you we have corrected this error and the updated sentence is listed below.

(Lines 83-86): “We used a combination of Current Procedural Terminology (CPT) codes from surgical logs and hospital billing data with medical device logs for breast implants and expanders from our integrated Electronic Health Record (EHR) to identify patients undergoing primary mastectomy with reconstruction.”

4. The headings of all tables should be edited in order to be easier readable

Author Response: Thank you we updated all the table headings to font size 10 to be easier to read.

The results of this large study are of an increase interest for the scientific community and may help (after future systematic reviews / meta-analyses will be made) in the decision-making process breast reconstruction strategy after mastectomy for cancer.

Author Response: Thank you for your thoughtful comments and thorough review. We appreciate the opportunity to further improve our paper.

 

Reviewer 2 Report

Comments and Suggestions for Authors

This manuscript is impressive because of the large number of included patients. However, I believe that in some aspects it is painting with a wide brush what presents many subtleties which are glossed over. This study has a lot to say but may fail to display the nuances and challenges in reconstructive pathways, where sometimes one procedure may not be enough to achieve a reconstruction, requiring staged procedures or serial interventions. My biggest concern is that reoperations are not categorized as urgent or elective, which is absolutely vital for understanding what this research is warning us about. Are IBR more prone to urgent reoperations, or to elective revisional procedures? Additionally, it does not distinguish procedures intended for secondary breast reconstruction when a primary procedure failed, compared to revisional procedures intended to improve successful outcomes. These are both limitations which hinder the interpretation of your findings and merit some consideration. Additionally, please find some more comments listed below:

 

SIMPLE SUMMARY:

• The first sentence feels incomplete. Please revise the statement by giving it a complete sense.

 

ABSTRACT:

• Some findings are missing: What was the significance of the difference for first reoperations? No p-value or SMD in the abstract.
• You mentioned analyzing mortality but did not provide pertinent results. Implement.

 

INTRODUCTION:

• This manuscript highlights the inconsistencies in the definition of “delayed” when addressing breast reconstruction timing. Tissue expanders are most commonly categorized under immediate reconstruction, but their classification can depend on timing and clinical intent. In some contexts, tissue expander-based reconstruction can be considered delayed-immediate reconstruction if the final reconstruction is intentionally postponed due to factors like postmastectomy radiation therapy. In contrast, if the expander is placed months or years after the mastectomy, it is considered delayed breast reconstruction. In your manuscript, some patients that received an expander but later a flap were categorized as “delayed”. As such, you should provide a stronger accent on this matter in order to give the readership an unequivocable understanding of what you mean by “immediate” and “delayed”.
• I believe that the introduction is missing the fact that pursuing an immediate vs delayed breast reconstruction is strongly influenced by geographical factors because of sociodemographic and economic disparities. A study from 2008 reported that approximately 38% of women undergoing mastectomy received immediate breast reconstruction, also highlighting that teaching hospitals and facilities with surgical training programs were more likely to offer autologous reconstruction techniques, including advanced microsurgical procedures. [PMID: 23271515] Another analysis of data from 2010 to 2011 found that 45% of women who underwent mastectomy received immediate breast reconstruction. The study revealed that hospitals in highly competitive markets had higher rates of immediate reconstruction (56.4%) compared to those in non-competitive markets (34.5%). [PMID: 30327971]

 

MATERIALS AND METHODS:

• You mentioned that “BR occurred within 0 to 14 days post-mastectomy, while delayed reconstruction, 99 occurring at least 42 days post-mastectomy”. What happens to patients between 15 and 41 days? In which group are they allocated?
• What was the range of time in which you assessed reoperations? Any length of time from mastectomy? This needs to be specified explicitly even in the abstract.

 

RESULTS:

• Your findings are in line with the fact that tissue expander followed by implant replacement continues to be the most dominantly performed reconstruction, which I believe deserves further attention. Is there a way to assess whether this trend decreased over the years or remained stable?
• Your findings suggest that there was covariate imbalance between immediate and delayed reconstruction for the following:
  • Smoking, suggesting more IBR patients were active smokers, despite having more patients who have never smoked in this same group. Is there a way to speculate that active smoking may have been a possible cause for complications requiring revision?
  • Laterality, suggesting more IBR patients received a bilateral procedure. Clarify if this is a bilateral mastectomy or whether that includes other separate balancing procedures on the contralateral side of the mastectomy. Could a bilateral procedure have increased complication rates warranting reoperation?
  • Radiotherapy, suggesting more IBR patients have received radiotherapy. It would have been useful to understand as a sub-analysis which types of reconstructions have been received by these patients in order to understand the implications and outcomes more clearly. Additionally, radiotherapy increases the rate of complications in all reconstructions which might also have influenced reoperation rates. Could this have also been a contributor?
• I have mixed feelings about findings from Table 2 as well as ASA score from Table 1: the fact that there are no statistically significant differences in terms of comorbidities between IBR and delayed reconstructions suggests that the broad sample size cancels out potential selection errors for these variables. However, what this also suggests is that the choice of whether to pursue a reconstruction immediately or not was likely not based on patient conditions and comorbid status, but was rather dependent on different reasons, which should be identified and discussed. Geographical i.e. unavailability of plastic surgeons providing a full range of surgical options? Economic and insurance-based?
• Autologous IBR had a higher risk of reoperation compared to expander-flap patients from the delayed group, suggesting that immediate flaps may be at a higher risk of reoperation from complications compared to delayed flap. This is consistent with findings from Beugels et al. [PMID: 29399731], although contrasting evidence has later found no difference. [PMID: 36077807] This merits additional discussion.
• The fact that delayed reconstructions undergo slightly fewer reoperations deserves some consideration as all these patients underwent an additional procedure which was the mastectomy separately. In hindsight, this should have been included in the calculation from the start. While this interpretation of your findings might seem shrewd, I encourage the authors to discuss the reality of their results and in which way they can benefit clinicians when counselling patients about whether to recommend an immediate or delayed reconstruction.

 

DISCUSSION:

• “Procedures for patients undergoing (CPT: 15772, 15772) after primary reconstruction were not counted as a reoperation (n=2,322). Some surgeons routinely performed fat-grafting after implant-based or autologous reconstructions, while others did not. This exclusion was based on the challenge of distinguishing between planned and unplanned fat grafting, and we opted to exclude procedures solely involving fat grafting from our outcome measures.” Define CPT code as “fat grafting”. Furthermore, this exclusion makes reconstructive pathway with various serial procedures such as fat grafting for fully autologous reconstructions much harder to assess. [PMID: 35499543] This is a very relevant limitation that needs to be acknowledged and addressed.
• While this research take into account the differences in terms of reoperations, it does not address cost-effectiveness of the various options, and most importantly patient reported outcome measures which I believe should be the driving force behind the choice of a reconstructive strategy. Please discuss further.
• It is my understanding that the rate of reoperations is likely not due to surgical complexity, since reoperation rate did not vary between autologous IBR with flaps and expander-flaps from the delayed groups. This deserves further consideration. However, the fact that duration of surgeries could not be analyzed is a limitation worth acknowledging since it is a relevant contributor to complication rates.
• The number of women undergoing reoperations with secondary breast reconstruction procedures varies depending on the initial reconstructive options, not just the timing. In fact, a study analyzing data from England reported that, over an 8-year period, approximately 18% of women who had implant-based immediate breast reconstruction underwent secondary reconstruction procedures. In contrast, only about 2% of women with latissimus dorsi flap reconstructions (with or without implants) required secondary procedures during the same timeframe. [PMID: 36998148] Similarly, research from the United States indicated that secondary revision rates were significantly higher after two-stage expander and implant reconstruction compared to autologous reconstruction. Unplanned revisions were needed in 59.2% of patients with expander-implants, whereas 34.4% of those with autologous reconstruction required such procedures. [PMID: 31764633] These findings suggest that the likelihood of undergoing secondary breast reconstruction is influenced by the initial reconstruction method, with implant-based procedures associated with higher rates of subsequent interventions. This needs to be addressed, as the sole interpretation of timing without a detailed context of reconstructive technique may be misleading.
• I cannot find a subgroup analysis on the effects of radiotherapy on reoperation rates. Patients who have received radiotherapy are at a much higher rate of secondary surgical procedures, and this should be addressed. [PMID: 35499543; 33425618]
• What was the mortality in each group? Was it influenced by surgical complexity? An Italian study on 99,690 patients who received implants, of which 57,369 were for breast reconstructions, found no cases of perioperative mortality. [PMID: 36376583] Please implement data if possible and address further.

Author Response

This manuscript is impressive because of the large number of included patients. However, I believe that in some aspects it is painting with a wide brush what presents many subtleties which are glossed over. This study has a lot to say but may fail to display the nuances and challenges in reconstructive pathways, where sometimes one procedure may not be enough to achieve a reconstruction, requiring staged procedures or serial interventions. My biggest concern is that reoperations are not categorized as urgent or elective, which is absolutely vital for understanding what this research is warning us about. Are IBR more prone to urgent reoperations, or to elective revisional procedures? Additionally, it does not distinguish procedures intended for secondary breast reconstruction when a primary procedure failed, compared to revisional procedures intended to improve successful outcomes. These are both limitations which hinder the interpretation of your findings and merit some consideration. Additionally, please find some more comments listed below:

Author Response: Thank you for your comments and thorough review of our manuscript. I understand the hesitations that you list above. As you have noted this is a very large cohort study and to our knowledge one of the largest and most recent cohorts assessing reoperation based on reconstructive timing which is particularly relevant given the increases in IBR in the past 10 years.

Unfortunately, larger cohort studies will miss some of the nuance and surgical details that can be assessed in smaller clinical studies. The purpose of our study was not to compare differences in reconstructive pathways but to look at the rate and risk of 1^st and multiple reoperations by reconstructive timing, and to further assess these outcomes based on different reconstructive modalities. While we do not label reoperations as urgent or elective, we account for initial planned first reoperations by taking into account the chosen reconstructive modality (ie for expander-implant the first surgery after the implant was placed was counted rather than after the expander placement) we are able to assess the rate of reoperation and the number of reoperations (counting up to 5) with an average follow-up of 5.9 years (±3.8 years). A few of the plastic surgeons involved on this project felt it was critical to know the burden of reoperation (urgent or not) based on timing so that could be communicated to the patient when discussing reconstruction options. We hope future clinical studies will be able to elucidate some of the nuances mentioned above in complex reconstructive pathways. We have listed some of the limitations mentioned above in the discussion.

Lines (318-324): “There are some noted limitations of our study. We did not assess differences in simple compared to more radical or information on nipple reconstruction which both have been known to affect the risk of return to the OR. Additionally, we did not have chemotherapy treatment information, particularly Tamoxifen, which may affect wound healing and in-crease patient morbidity and reoperation because of complications. We were also unable to detail information on AJCC Stage at mastectomy and the timing and dosage of patient radiotherapy.”

 

SIMPLE SUMMARY:

• The first sentence feels incomplete. Please revise the statement by giving it a complete sense.

Author response: Thank you; we have fixed this error.

 (Lines 14-16): “We performed one of the largest recent assessments of risk of reoperation by reconstruction timing while accounting for radiotherapy and reconstruction technique.”

 

ABSTRACT:

• Some findings are missing: What was the significance of the difference for first reoperations? No p-value or SMD in the abstract.

Author Response: The crude incidence and adjusted hazard ratios are given on lines (37-39) in the abstract

“Crude incidence of 1st reoperation was 33.04% vs 31.72% in IBR vs delayed patients and the risk of reoperation was 18% higher in IBR patients (HR=1.18, 95% CI=1.12-1.25).”

Due to space constraints were unable to list all of the imbalanced covariates and accompanying SMDs in the abstract but we have added the imbalanced covariates to the abstract. See below.

(Lines 35-37):” The following covariates were imbalanced (standardized mean difference [SMD] ≥0.20) between IBR and delayed groups: BMI, smoking status, year of mastectomy, bilateral, and reconstruction type.”

• You mentioned analyzing mortality but did not provide pertinent results. Implement.

Author response:  Mortality and membership termination were included as competing risks for reoperation in the analysis. Since mortality is not the primary or secondary outcome for the paper due to space constraints it was left out of the abstract. Information on both mortality and membership termination are listed in the results section of the paper.

(Lines 184-186) “A total of n=1,171 patients died during follow-up (IBR: 4.7% and Delayed 6.1%) and n=3003 patients terminated their membership (IBR: 12.8% and Delayed: 12.9%).”  

INTRODUCTION:

• This manuscript highlights the inconsistencies in the definition of “delayed” when addressing breast reconstruction timing. Tissue expanders are most commonly categorized under immediate reconstruction, but their classification can depend on timing and clinical intent. In some contexts, tissue expander-based reconstruction can be considered delayed-immediate reconstruction if the final reconstruction is intentionally postponed due to factors like postmastectomy radiation therapy. In contrast, if the expander is placed months or years after the mastectomy, it is considered delayed breast reconstruction. In your manuscript, some patients that received an expander but later a flap were categorized as “delayed”. As such, you should provide a stronger accent on this matter in order to give the readership an unequivocable understanding of what you mean by “immediate” and “delayed”.

Author response: Thank you for your valuable clinical insights and comments. We acknowledge that since this is real world data there are patients that have reconstruction pathways that are outside what could be considered the clinical norm. We do not believe that an examination of this in the introduction is necessary as we are trying to provide sufficient background on the current literature and knowledge of reconstruction timing and modality. We have included these definitions of immediate and delayed in the “exposure” section of the methods so the reader can understand the breakdown of groups into immediate and delayed by timing from mastectomy.

(Lines 101-108):” The exposure of interest was timing of breast reconstruction following primary mastectomy. IBR occurred within 0 to 14 days post-mastectomy, while delayed reconstruction, occur-ring at least 42 days post-mastectomy, was modeled as the reference group. Any cases where laterality could not be determined were excluded. Delayed reconstruction was modeled as the reference group.”

(Lines 150-153): “Reconstructions were categorized into one-stage approach (direct-to-implant, flap with implant, primarily autologous reconstruction without an expander), two-stage approach (tissue expander followed by either implant or autologous reconstruction), and tissue expander with or without further reconstruction.”

• I believe that the introduction is missing the fact that pursuing an immediate vs delayed breast reconstruction is strongly influenced by geographical factors because of sociodemographic and economic disparities. A study from 2008 reported that approximately 38% of women undergoing mastectomy received immediate breast reconstruction, also highlighting that teaching hospitals and facilities with surgical training programs were more likely to offer autologous reconstruction techniques, including advanced microsurgical procedures. [PMID: 23271515] Another analysis of data from 2010 to 2011 found that 45% of women who underwent mastectomy received immediate breast reconstruction. The study revealed that hospitals in highly competitive markets had higher rates of immediate reconstruction (56.4%) compared to those in non-competitive markets (34.5%). [PMID: 30327971]

Author response: Thank you for your comments. We acknowledge that sociodemographic factors can often impact patient surgical access. We have an integrated, private healthcare system that does not include any teaching hospitals or training programs. Our healthcare plan is not comparable to most private or public insurance because we own our hospitals as part of the integrated system. Additionally, to ensure data completeness we only included patients in the study that had their initial procedures at a Kaiser Permanente Hospital. More than 90% of our study cohort is from either northern or southern California and based on 2022 census data 94.2% of Californians reside in urban areas, meaning access to a Kaiser Permanente facility based on geographic distances are more comparable. We listed the yearly breakdown of immediate versus delayed reconstructions in Table 1 and account for this in the analysis. Since patient surgical access is not the focus of this paper we believe including this information would be outside the scope of the introduction but we have a section in the limitations acknowledging that we are not able to account for all reasons that influence patient and doctor choice:

(Lines 324-326):” Our analysis may have residual confounding. We cannot completely account for the com-plex factors and decision-making process between patients and clinical teams for breast reconstruction or reoperation.”

Reference URL: https://www.census.gov/newsroom/press-releases/2022/urban-rural-populations.html#:~:text=Of%20the%2050%20states%2C%20California,California%20(37%2C259%2C490) Accessed 3/19/25

 

MATERIALS AND METHODS:

• You mentioned that “BR occurred within 0 to 14 days post-mastectomy, while delayed reconstruction, 99 occurring at least 42 days post-mastectomy”. What happens to patients between 15 and 41 days? In which group are they allocated
•  
• Author response: Thank you for your comments. We have amended this oversight and added the following to the methods.

(Lines 103-107): “We excluded reconstructions performed between 15- to 42-days post-mastectomy. Patients in this period would have a chance to heal their mastectomy skin flaps, reducing the risks compared to the immediate group, but they lacked the extended healing time of the delayed group.”

Reference: Matsen CB, Mehrara B, Eaton A, et al. Skin Flap Necrosis After Mastectomy With Reconstruction: A Prospective Study. Annals of surgical oncology 2016;23:257-264

 

• What was the range of time in which you assessed reoperations? Any length of time from mastectomy? This needs to be specified explicitly even in the abstract.

Author response: Thank you for your comment. As time to first reoperation could occur at any point after completion of first or second stage reconstruction, we did not implement any minimum follow-up and have included all specified patient follow-up time in the cause-specific Cox proportional hazards models. The study end date is 12/31/2022 and is listed below in the methodology.

(Lines 110-112): “The primary outcome of interest was (1) time to first return to surgery on the breast for any reason and (2) multiple returns to surgery (1-5) on the breast for any reason after initial (first or second stage) reconstruction was complete.”

(Lines 119-121): “After surgery, patients were continuously monitored for death, outcome of interest, loss to follow-up through healthcare membership termination, or study end date (12/31/2022).”

We have added this sentence to the abstract:

(Lines 32-33): “Patients were continuously monitored for death, outcome of interest, loss to follow-up through healthcare membership termination, or study end date (12/31/2022).”

 

RESULTS:

• Your findings are in line with the fact that tissue expander followed by implant replacement continues to be the most dominantly performed reconstruction, which I believe deserves further attention. Is there a way to assess whether this trend decreased over the years or remained stable?

Author Response: We greatly appreciate your clinical knowledge and comments. Unfortunately, this is outside the scope of our stated objectives although we hope to investigate this further in a future study.

• Your findings suggest that there was covariate imbalance between immediate and delayed reconstruction for the following:
• Smoking, suggesting more IBR patients were active smokers, despite having more patients who have never smoked in this same group. Is there a way to speculate that active smoking may have been a possible cause for complications requiring revision?

Author response: Thank you for your comment. Based on the literature, current smoking is a well-known complication for surgery due to many factors including wound healing (doi:10.1001/jamanetworkopen.2025.0295). Patients with IBR were less likely to be active smokers (0.8% vs 1.2%) although this group represents a very small proportion of our cohort compared to never smokers (IBR=73.6% vs Delayed 67.5%). As we did not differentiate between elective reoperations and those for complications and our findings are a higher percentage of first reoperations in IBR not delayed, we believe this would not contribute value to our discussion.

 

Laterality, suggesting more IBR patients received a bilateral procedure. Clarify if this is a bilateral mastectomy or whether that includes other separate balancing procedures on the contralateral side of the mastectomy. Could a bilateral procedure have increased complication rates warranting reoperation?

Author response: Thank you for your comment. We apologize if this was not clear in the methodology, but bilateral procedures were defined as bilateral mastectomy.

• Radiotherapy, suggesting more IBR patients have received radiotherapy. It would have been useful to understand as a sub-analysis which types of reconstructions have been received by these patients in order to understand the implications and outcomes more clearly. Additionally, radiotherapy increases the rate of complications in all reconstructions which might also have influenced reoperation rates. Could this have also been a contributor?

Author response: Thank you for your comment. At baseline radiotherapy was comparable between groups and slightly higher in the delayed group (delayed 37.4% vs IBR 35.2%). We apologize but are unsure what is being requested-can you provide further clarification?

• I have mixed feelings about findings from Table 2 as well as ASA score from Table 1: the fact that there are no statistically significant differences in terms of comorbidities between IBR and delayed reconstructions suggests that the broad sample size cancels out potential selection errors for these variables. However, what this also suggests is that the choice of whether to pursue a reconstruction immediately or not was likely not based on patient conditions and comorbid status, but was rather dependent on different reasons, which should be identified and discussed. Geographical i.e. unavailability of plastic surgeons providing a full range of surgical options? Economic and insurance-based?

Author response: Thank you for your comment. ASA is a validated risk factor for surgical outcomes. Elixhauser comorbidities were included because we believed that these could also influence reconstruction timing. We do not agree that a large sample size “cancels out” the effect of comorbidities rather our patient population may be healthier and more homogenous with regard to an elective procedure than other hospital systems that use Medicare, Medicaid, or less comprehensive private insurance plans. If you assess the distribution of comorbidities in Table 2 although approximately 30% of all patients had no comorbidities, a similar percentage had at least 1. We discuss the distribution of our patient comorbidities and characteristics as related to the literature in the discussion section (below). We have already discussed the differences in our health plans and integrated hospital systems earlier in this response. All of our patients had private insurance or a combination of private and other forms.

(Lines 303-317): “At baseline in our study population patient characteristics that may increase shorter term reoperation because of complications from wound healing, including advanced age, higher ASA or comorbidities, diabetes, and radiotherapy, were balanced between reconstruction timing groups (SMD<0.20). This may explain some of the differences we found in our population compared to the literature regarding risk of reoperation, particularly in the first year. Additionally, none of the Elixhauser comorbidities assessed were different be-tween reconstruction timing groups. Finally, unlike many other analyses that have assessed complications or reoperation-based outcomes, we accounted for competing events, including mortality and loss to follow-up. In the United States our integrated healthcare system is unique in this ability to capture outcomes that may bias results due to incomplete information and are able to provide results based on longer-term follow-up. Additionally, we have detailed information on patient covariates and comorbidities which can reduce confounding in effect estimates. Mastectomy and reconstruction procedures were performed by many diverse surgical teams at 38 different medical centers so our findings may be more generalizable.”

Autologous IBR had a higher risk of reoperation compared to expander-flap patients from the delayed group, suggesting that immediate flaps may be at a higher risk of reoperation from complications compared to delayed flap. This is consistent with findings from Beugels et al. [PMID: 29399731], although contrasting evidence has later found no difference. [PMID: 36077807] This merits additional discussion.

Author response: Thank you for your comment. We apologize for any confusion, but we did not directly compare autologous IBR to expander-flap from the delayed group. In the subgroup analysis we kept each reconstruction modality (direct to implant, expander implant, etc) as a category comparing the risk of immediate reconstruction to delayed reconstruction in that group. For example, patients that had a two-stage expander-implant placement immediately after reconstruction compared to patients who had a delayed two stage expander-implant reconstruction, therefore we are unable to compare our findings with the literature discussed above.

• The fact that delayed reconstructions undergo slightly fewer reoperations deserves some consideration as all these patients underwent an additional procedure which was the mastectomy separately. In hindsight, this should have been included in the calculation from the start. While this interpretation of your findings might seem shrewd, I encourage the authors to discuss the reality of their results and in which way they can benefit clinicians when counselling patients about whether to recommend an immediate or delayed reconstruction.
• Author response: Thank you for your comment. The purpose of our paper was not to look at the total operations but the risk of reoperation after reconstruction was complete, regardless of the modality chosen. There is a difference here based on patient expectations. Further, we hope to provide additional information to help shape patient expectations for the risk of reoperation given what is planned initially with the patient’s clinical team. We realize that risk of reoperation is not the only factor given the high rate of patient satisfaction and high patient reported outcome measures following immediate compared to delayed procedures in the literature. The greatly increased adoption of IBR over the 10 years in our healthcare system when our study was conducted highlights the success of IBR procedures in patients that have very similar patient factors outside of BMI and smoking status. Our goal was to conduct a study that could hopefully provide additional information on the risk of reoperation (1^st and multiple) which can be used to counsel patients when planning reconstruction procedures. 

DISCUSSION:

• “Procedures for patients undergoing (CPT: 15772, 15772) after primary reconstruction were not counted as a reoperation (n=2,322). Some surgeons routinely performed fat-grafting after implant-based or autologous reconstructions, while others did not. This exclusion was based on the challenge of distinguishing between planned and unplanned fat grafting, and we opted to exclude procedures solely involving fat grafting from our outcome measures.” Define CPT code as “fat grafting”. Furthermore, this exclusion makes reconstructive pathway with various serial procedures such as fat grafting for fully autologous reconstructions much harder to assess. [PMID: 35499543] This is a very relevant limitation that needs to be acknowledged and addressed.

Author response: Thank you for your comment. We apologize but are unsure what is being requested regarding CPT codes defined as fat grafting. Can you please provide further details?

• While this research take into account the differences in terms of reoperations, it does not address cost-effectiveness of the various options, and most importantly patient reported outcome measures which I believe should be the driving force behind the choice of a reconstructive strategy. Please discuss further.

Author response: Thank you for your comment. Our study objective was to assess reoperations after completion of first and second stage modalities by reconstruction timing, and we believe a cost effectiveness analysis is outside the scope of our study. Additionally, we do not agree that cost is the driving force behind the choice of a reconstructive strategy as there are many factors that must be considered given the complex pathway that a patient must navigate when receiving treatment for breast cancer.

 

It is my understanding that the rate of reoperations is likely not due to surgical complexity, since reoperation rate did not vary between autologous IBR with flaps and expander-flaps from the delayed groups. This deserves further consideration. However, the fact that duration of surgeries could not be analyzed is a limitation worth acknowledging since it is a relevant contributor to complication rates.

 

Author response: Thank you for your comment. We did not directly compare autologous IBR with flaps and expander flaps from the delayed group so unfortunately, we cannot comment on the differences in surgical complexity between these groups. We had initially planned on including length of stay and surgical duration but given that IBR patients had mastectomy plus reconstruction while delayed patients had reconstruction alone the difference in time and complexity seemed to be inherent in the categories and could also be considered to be separate from a baseline measure which is completed prior to index surgery.

 

The number of women undergoing reoperations with secondary breast reconstruction procedures varies depending on the initial reconstructive options, not just the timing. In fact, a study analyzing data from England reported that, over an 8-year period, approximately 18% of women who had implant-based immediate breast reconstruction underwent secondary reconstruction procedures. In contrast, only about 2% of women with latissimus dorsi flap reconstructions (with or without implants) required secondary procedures during the same timeframe. [PMID: 36998148] Similarly, research from the United States indicated that secondary revision rates were significantly higher after two-stage expander and implant reconstruction compared to autologous reconstruction. Unplanned revisions were needed in 59.2% of patients with expander-implants, whereas 34.4% of those with autologous reconstruction required such procedures. [PMID: 31764633] These findings suggest that the likelihood of undergoing secondary breast reconstruction is influenced by the initial reconstruction method, with implant-based procedures associated with higher rates of subsequent interventions. This needs to be addressed, as the sole interpretation of timing without a detailed context of reconstructive technique may be misleading.

Author response: Thank you for your comment. All patients at index procedure underwent a primary elective mastectomy and not secondary breast reconstruction procedures. If you can elaborate on what you mean as secondary reconstruction procedures following the initial stage of reconstruction, we can hopefully provide additional detail and potentially discussion. We have accounted for reconstruction modality by conducting a subanalysis to compare reconstruction timing within each group (direct to implant, expander-implant, etc).

• I cannot find a subgroup analysis on the effects of radiotherapy on reoperation rates. Patients who have received radiotherapy are at a much higher rate of secondary surgical procedures, and this should be addressed. [PMID: 35499543; 33425618]

Author response: Thank you for your comment. We did not include a subgroup analysis on the effects of radiotherapy on reoperation rates as our reported baseline percentages were similar between groups (IBR: 35.2% vs Delayed 37.4%) and in balance based on the SMD. Follow-up time for analysis in patients started at baseline although we acknowledge in the literature that as stated patients who receive radiotherapy are at a higher rate of secondary surgical procedures.

What was the mortality in each group? Was it influenced by surgical complexity? An Italian study on 99,690 patients who received implants, of which 57,369 were for breast reconstructions, found no cases of perioperative mortality. [PMID: 36376583] Please implement data if possible and address further.

Author response: Thank you for your comment.  Mortality and membership termination were included as a competing risks for reoperation in the analysis. Can you please elaborate one what you are defining as surgical complexity so we can comment further? Information on both mortality and patient membership termination are listed in the results.

(Lines 184-186) “A total of n=1,171 patients died during follow-up (IBR: 4.7% and Delayed 6.1%) and n=3003 patients terminated their membership (IBR: 12.8% and Delayed: 12.9%).”  

 

 

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for taking the time to respond to my queries. The implementations you provided are appropriate but I hope some more minor corrections can also be added. Please see my residual concerns listed below:

–            While I understand that distinguishing between urgent and elective reoperations may be beyond the scope of your manuscript, I believe that the readership might be mislead into thinking that such information could be available in your work, and a brief implementation of this should find its place with the other limitations you implemented in the discussion.

–            Some of your international readers may not be familiar with CPT codes. As such, please consider defining what the CPT codes 15771 and 15772 stand for in your materials and methods. 

–            Can surgical complexity (intended as duration of surgery) be implemented as a factor affecting morbidity/mortality?

Author Response

Thank you for taking the time to respond to my queries. The implementations you provided are appropriate, but I hope some more minor corrections can also be added. Please see my residual concerns listed below:

Author response: Thank you for taking the time to review our responses and improve our manuscript. We have responded to the corrections below.

1. While I understand that distinguishing between urgent and elective reoperations may be beyond the scope of your manuscript, I believe that the readership might be mislead into thinking that such information could be available in your work, and a brief implementation of this should find its place with the other limitations you implemented in the discussion.

 

Author response 1: Thank you, we agree and have provided this as an additional limitation in the discussion section.

 

(Lines 322-325): “We were unable to assess the reason for reoperation and identify reoperations for complications (e.g. infection, hematoma) as it would have required extensive chart review and was beyond the scope of our project.”

 

2. Some of your international readers may not be familiar with CPT codes. As such, please consider defining what the CPT codes 15771 and 15772 stand for in your materials and methods. 

Author response 2: Thank you, that is an excellent point. We have included a description in the methodology.

 

(Lines 122-126): " Procedures for patients undergoing autologous fat grafting (Current Procedural Terminology [CPT]: 15771, 15772) after primary reconstruction were not counted as a reoperation (n=2,322). These codes indicate procedures for grafting of autologous fat harvested by liposuction technique to trunk, breasts, scalp, arms, and/or legs with a volume of 50 cc or less (CPT: 15771) and report each additional 50cc of harvested fat (CPT: 15772)". 

 

3. Can surgical complexity (intended as duration of surgery) be implemented as a factor affecting morbidity/mortality?

Author response 3: While we are unable to include this information in the analysis we have included this comparison in the results as well as a comparison of patients with reoperation and those who died during follow-up versus those without.

(Lines 193-202): Overall, mean operating time was longer in patient that underwent immediate reconstruction (IBR: 231.1, Standard deviation [STD]±137.1 vs. Delayed: 131.0, STD±60.3), and this time was higher for immediate reconstruction patients that underwent at least one reoperation (mean 241.3, STD± 130.1), but lower in those  who delayed reconstruction (mean: 126.0, STD± 57.7). These differences potentially indicate the surgical complexity of patients who underwent immediate reconstruction. Patients who died during follow-up had lower mean operating time regardless of reconstruction timing compared to overall groups (IBR: 190, STD±137.5 and delayed129.3, STD±62.8).