Authors’ reply to Malhotra

We are grateful to Dr. Malhotra[1] for his critical review of our manuscript titled “Clinical profile and outcomes of patient with endometrial cancer from Northwest India: A retrospective study.”[2] We sincerely appreciate their time and expertise in evaluating our work and welcome the opportunity to respond to the statistical and methodological concerns raised. We have reanalyzed the data as suggested; however, these revisions do not alter the interpretation of our results. Due to the space constraints, the updated figures are not included in the current manuscript but are available upon request. The corrected data can be made available from Dr. Ashwin Philips at [email protected], starting from the date of publication, until 10 years after publication. Requests beyond this timeframe will be considered on a case-by-case basis. 1. Univariable and multivariable Cox regression analyses We acknowledge the oversight in omitting the detailed results of our Cox regression analyses. We have now included the results of both univariable and multivariable Cox regression analyses for disease-free survival (DFS) and overall survival (OS), which are now presented in Tables 1T2T3-4. These analyses identified tumor grade and stage as independent prognostic factors for both DFS and OS. For DFS, higher tumor grade was associated with higher risk of recurrence (HR 2.53; 95% CI: 1.24-5.16; P, 0.011), and early-stage disease (Stage I-II) was associated with a lower risk compared to advanced stage (Stage III-IV) (HR 0.26; 95% CI: 0.09-0.71; P, 0.009). Similarly, for OS, higher tumor grade was independently associated with an increased risk of death (HR 4.84; 95% CI: 1.13-20.76; P, 0.034), and early-stage disease was again associated with better survival outcomes (HR 0.19; 95% CI: 0.04-0.85; P, 0.030). These findings highlight the prognostic significance of tumor grade and stage in endometrial cancer, with higher grade independently correlating with worse survival outcomes even after adjusting for disease stage. Table 1: Univariable cox regression for disease-free survival (DFS)Table 2: Univariable Cox regression for overall survival (OS)Table 3: Multivariable Cox regression for disease-free survival (DFS)Table 4: Multivariable Cox regression for Overall Survival (OS) 2. Follow-up duration and survival estimates We agree that a follow-up duration of 5.67 years may not be sufficient to accurately estimate 5-year OS and DFS in all cases. However, the median follow-up duration in our study was 13.1 months, and we used Kaplan-Meier survival analysis to estimate survival probabilities. While the follow-up duration may limit the precision of long-term survival estimates, we believe the results provide valuable insights into the clinical outcomes of endometrial cancer in our region. 3. Definition of disease-free survival (DFS) We appreciate your observation regarding the definition of DFS. In our study, DFS (operational definition) was calculated from the date of diagnosis (confirmed histopathology report) to the date of documented progression, death, or last follow-up. While this approach is consistent with some studies in the literature,[3,4] we acknowledge that calculating DFS from the date of surgery is more conventional and clinically relevant, in our study, 98% of patients underwent upfront surgery. The histopathology report used for defining DFS was post operative in nearly all cases. 4. Confidence intervals (CI) for survival probabilities We accept the earlier error in reporting confidence intervals. The CIs should correspond to the survival probabilities, not the median survival times. The corrected 3-year, 4-year, and 5-year survival probabilities with 95% CIs are now included herewith in Table 5. Table 5: Survival outcomes 5. Labelling of the X-axis in survival curves The x-axis of our Kaplan-Meier curves reflected time since surgery (in months) and the y-axis represented disease-free survival probability. We agree that the x-axis of the survival curve should be labeled at 12-month intervals to align with the reported 3-year, 4-year, and 5-year OS and DFS outcomes and we will include these changes in our future analyses. 6. Interpretation of Log-Rank test results We appreciate the reviewer’s insightful comment regarding the interpretation of the log-rank test. While the log-rank test assesses differences in survival distributions over the entire follow-up period, it does not directly compare survival probabilities at specific time points. In line with your suggestion, we conducted z-tests to compare survival outcomes at fixed time points between early-stage (Stage I-II) and advanced-stage (Stage III-IV) groups. The z-test for DFS demonstrated a statistically significant difference between the groups (z, −3.9, P < 0.001), with DFS rates of 78.1% in the early-stage group and 16.2% in the advanced-stage group. Similarly, the z-test for OS also showed a significant difference (z, −2.45, P, 0.014), with OS rates of 95.7% for early-stage disease and 34.1% for advanced-stage disease. These findings underscore the prognostic relevance of disease stage, particularly at clinically meaningful time points. 7. Censoring and risk of bias We acknowledge the potential for bias due to censoring, particularly given the short follow-up in some patients. While we attempted to mitigate this by including only patients with at least 3 months of follow-up, we recognize this remains a limitation of our retrospective design. 8. Survival data collection We obtained the survival data from electronic medical records and patient files. Due to the ethical and logistical constraints, we did not contact patients or families to obtain follow-up data. We sincerely thank Dr. Malhotra once again for their thoughtful critique, which has led to important clarifications and improvements in our manuscript. Being a retrospective study, there have been shortcomings especially from a new center. As a next step, we have initiated a multicentric observational study on endometrial cancers, which will allow for more robust survival analyses with improved data quality and follow-up. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.