Pain and Health-related Quality of Life with Biweekly Versus Triweekly Cabazitaxel Schedule in Older Men with Metastatic Castration-resistant Prostate Cancer in the Multicenter, Randomized CABASTY Trial.

BACKGROUND AND OBJECTIVE: The CABASTY study showed that more frequent administration of a lower dose of cabazitaxel (CBZ) reduced toxicity in older men with metastatic castration-resistant prostate cancer (mCRPC), without compromising efficacy. Here, we investigated the impact of a biweekly CBZ schedule on patient-reported pain and health-related quality of life (HRQoL). METHODS: We randomized 196 patients from 25 centers (1:1, stratified by age and G8 score) to the biweekly CBZ16 (CBZ 16 mg/m2) experimental arm or the triweekly CBZ25 (CBZ 25 mg/m2) control arm (CABASTY study, NCT02961257). We assessed pain using the Numeric Pain Rating Scale and HRQoL using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. KEY FINDINGS AND LIMITATIONS: A total of 141 patients were available for a pain and 160 for an HRQoL analysis. Median time to pain progression (stratified hazard ratio [HR]: 1.7, confidence interval [CI]: 0.67-4.22, p = 0.3) and median time to first opiate use (stratified HR: 1.05, CI: 0.44-2.55, p = 0.9) did not differ between arms. We did not see a significant difference in median time to deterioration of FACT-P total score between treatments (stratified HR: 0.88, CI: 0.47-1.7, p = 0.7). Interestingly, the time to onset of several adverse events was significantly longer in the biweekly CBZ16 group. CONCLUSIONS AND CLINICAL IMPLICATIONS: HRQoL did not significantly differ between the biweekly CBZ16 and the standard schedule. Additionally, onset of some adverse events was delayed. These results may increase health care providers' confidence in using CBZ in older patients with mCRPC who are denied chemotherapy. PATIENT SUMMARY: Androgen receptor pathway inhibitors are often preferred to taxane chemotherapy as a treatment of second or subsequent line in older metastatic castration-resistant prostate cancer patients due to more frequent treatment-related toxicities. Here, we showed that quality of life and pain did not differ significantly with an adapted schedule of cabazitaxel (CBZ), compared with the standard regimen. This CBZ schedule could increase eligibility of older patients for chemotherapy.

Prognostic Factors for Long-Term Eribulin Response in a Cohort of Patients With HER2-Negative Metastatic Breast Cancer.

CONTEXT AND AIMS: Eribulin is used in taxane and anthracycline refractory HER2-negative metastatic breast cancers (MBC). Patients treated in pivotal clinical trials achieved low survival rates, therefore, the identification of prognostic criteria for long progression-free survival (PFS) is still an unmet medical need. In this study, we sought to determine potential prognostic criteria for long-term eribulin response in HER2-negative MBC. METHODS: Our retrospective cohort includes female patients with HER2-negative MBC treated with eribulin in Franche-Comté, France. We defined a long-term response as at least 6 months of eribulin treatment. The primary endpoint was the analysis of criteria that differ according to the progression-free survival. Secondary outcomes concerned overall survival and response rate. RESULTS: From January 2011 to April 2020, 431 patients treated with eribulin were screened. Of them, 374 patients were included. Median PFS was 3.2 months (2.8-3.7). Eighty-eight patients (23.5%) had a long-term response to eribulin. Four discriminant criteria allowed to separate PFS in 2 arms (PFS < 3 months or > 6 months) with a 78% positive predictive value: histological grade, absence of meningeal metastasis, response to prior chemotherapy, and OMS status. We have developed a nomogram combining these 4 criteria. Median overall survival was 8.5 months (7.0-9.5). CONCLUSION: Eribulin response in MBC can be driven by clinical and biological factors. Application of our nomogram could assist in the prescription of eribulin.

A novel risk classification model integrating CEA, ctDNA, and pTN stage for stage 3 colon cancer: a post hoc analysis of the IDEA-France trial.

BACKGROUND: We assessed the added value of incorporating carcinoembryonic antigen (CEA) to circulating tumor DNA (ctDNA) and pathological TN (pTN) stage for risk classification in stage 3 colon cancer (CC). PATIENTS AND METHODS: We retrospectively analyzed postoperative CEA values in patients with CC from the IDEA-France phase 3 trial. The relation between disease-free survival (DFS) and CEA was modeled through restricted cubic splines. Prognostic value of CEA, ctDNA, and pTN was assessed with the Kaplan-Meier method. Multivariate analysis was used to identify prognostic and predictive factors for DFS. RESULTS: Among 696 patients (35%), CEA values were retrievable, and for 405 (20%) both CEA and ctDNA were available. An optimized CEA threshold of 2 ng/mL was identified, the 3-year DFS was 66.4% for patients above the threshold and 80.9% for those below (HR, 1.74; 95% CI, 1.33-2.28, P < .001). In multivariate analysis, CEA ≥ 2 ng/mL contributed significantly to model variability, becoming an independent prognostic factor for DFS (HR, 1.82; 95% CI,1.27-2.59), alongside ctDNA (HR, 1.88; 95% CI, 1.16-3.03) and pTN (HR, 1.78; 95% CI, 1.24-2.54). A novel integrated risk classification combining CEA, ctDNA, and pTN stage reclassified 19.8% of pT4/N2 patients as low risk and 2.5% of pT3/N1 patients as high risk. This new classification demonstrated the 3-year DFS of 80.8% for low-risk patients and 55.4% for high-risk patients (HR, 2.66, 95% CI, 1.84-3.86, P < .001). CONCLUSIONS: Postoperative CEA value is a prognostic factor for DFS in stage 3 CC, independently of ctDNA and pTN. It advocates for systematic reporting in future adjuvant trials. Integrating both biomarkers with pTN could refine risk classification in stage 3 CC.

Survival Outcomes in Patients with Monobloc-Resected Stage IIC (pT4bN0) Colon Cancer: A Retrospective Observational Cohort Study.

BACKGROUND: Stage II colon cancer (CC) exhibits considerable prognostic heterogeneous. Our objective was to assess survival but also the prognosis impact of microsatellite instability (MSI) in patients with stage IIC (T4bN0M0) CC. PATIENTS AND METHODS: We conducted a retrospective observational study including all patients who had primary stage IIC CC resection between 2010 and 2020 in 2 expert centers. The primary endpoint was overall survival (OS) and disease-free survival (DFS) and time-to-relapse (TTR) were secondary endpoints. RESULTS: Sixty-six patients, median age of 74 years [30-95], were included, with 37.9% presenting MSI (n = 25). Organ invasion involved the last ileal loop (n = 17), another colonic segment (n = 15), omentum (n = 13), visceral peritoneum (n = 13), and the bladder (n = 4). Surgical quality criteria showed complete monobloc resection in all patients and 93.9% R0 resection. After a median follow-up of 5 years [3.5-6.6], the entire population showed a 5-year OS of 65.2% [53.0-80.3] and 5-year DFS of 53.5% [41.1-69.6], with 18.9% [6.8-29.4] experiencing relapses at 5 years. The MSI phenotype correlated with improved 5-year OS (75.5% [56.5-100] vs. 59.5% [44.9-79.0], HR 0.41 [0.17-0.99]; P = .04), but DFS and TTR did not differ. Adjuvant chemotherapy was administered to 34.9% of patients. Univariate analysis identified age > 65 years, MSI status, and the number of nodes as factors associated with OS. CONCLUSION: These data underline, in relation to a low rate of relapse, the lack of consensus regarding the appropriate indication for adjuvant chemotherapy in this high-risk stage II population.

A multicenter study evaluating efficacy of immune checkpoint inhibitors in advanced non-colorectal digestive cancers with microsatellite instability.

BACKGROUND: One randomized phase III trial comparing chemotherapy (CT) with immune checkpoint inhibitors (ICI) has demonstrated significant efficacy of ICI in deficient DNA mismatch repair system/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer. However, few studies have compared ICI with CT in other advanced dMMR/MSI-H digestive tumors. METHODS: In this multicenter study, we included patients with advanced dMMR/MSI-H non-colorectal digestive tumors treated with chemotherapy and/or ICIs. Patients were divided retrospectively into two groups, a CT group and an immunotherapy (IO) group. The primary endpoint was progression-free survival (PFS). A propensity score approach using the inverse probability of treatment weighting (IPTW) method was applied to deal with potential differences between the two groups. RESULTS: 133 patients (45.1/27.1/27.8% with gastric/small bowel/other carcinomas) were included. The majority of patients received ICI in 1st (29.1%) or 2nd line (44.4%). The 24-month PFS rates were 7.9% in the CT group and 71.2% in the IO group. Using the IPTW method, IO treatment was associated with better PFS (HR=0.227; 95% CI 0.147-0.351; p < 0.0001). The overall response rate was 26.3% in the CT group versus 60.7% in the IO group (p < 0.001) with prolonged duration of disease control in the IO group (p < 0.001). In multivariable analysis, predictive factors of PFS for patients treated with IO were good performance status, absence of liver metastasis and prior primary tumor resection, whereas no association was found for the site of the primary tumor. CONCLUSIONS: In the absence of randomized trials, our study highlights the superior efficacy of ICI compared with standard-of-care therapy in patients with unresectable or metastatic dMMR/MSI-H non-colorectal digestive cancer, regardless of tumor type, with acceptable toxicity.

Time to recurrence and its relation to survival after recurrence in patients resected for stage III colon cancer.

BACKGROUND: It is intuitively thought that early relapse is associated with poor survival after recurrence (SAR) in resected colon cancer (CC) patients, but this has never been formally studied. METHODS: We pooled data from stage III patients treated with oxaliplatin-based adjuvant therapy in two phase III trials, to analyse time to recurrence (TTR) and its relationship with SAR. TTR and SAR were also studied according to molecular status (mismatch repair (MMR), RAS, and BRAFV600E). Early relapsing patients were defined as patients having a TTR event within 12 months after starting adjuvant chemotherapy. RESULTS: 4548 stage III CC patients were included in the present analysis. Deficient MMR (dMMR) CC patients experienced fewer recurrences than proficient (p)MMR CC patients (18.8% versus 27.6%) but had a significantly shorter median TTR (mTTR; 0.74 versus 1.40 years, p < 0.0001). In pMMR patients, BRAF and RAS mutations were also associated with earlier mTTR as compared to double wild-type (WT) patients (0.99 versus 1.38 versus 1.54 years, respectively, p < 0.0001). Early recurrence occurred in 397 patients and was associated with a median SAR (2.2 versus 3.3 years, p = 0.0007). However, this association was mainly due to pMMR/RAS and BRAFV600E mutated tumours and was not confirmed in dMMR and pMMR/double WT subgroups. CONCLUSION: In resected stage III CC treated with standard oxaliplatin-based adjuvant therapy, TTR varies between dMMR, pMMR/RAS, or BRAFV600E mutated and pMMR/double WT tumours. In addition, early relapse is associated with poor survival, mainly due to patients resected for a pMMR/RAS or BRAFV600E mutated tumour.

Does KONO-S anastomosis reduce recurrence in Crohn's disease compared to conventional ileocolonic anastomosis? A nationwide propensity score-matched study from GETAID Chirurgie Group (KoCoRICCO study).

BACKGROUND AND AIMS: Postoperative recurrence is a major concern in Crohn's disease. The Kono-S anastomosis has been described to reduce the rate of recurrence. However, the level of evidence for its effectiveness remains low. The KoCoRICCO study aimed to compare outcomes between Kono-S anastomosis and conventional anastomosis in two nationwide prospective cohorts. METHODS: Adult patients with Crohn's disease who underwent ileocolonic resection with Kono-S anastomosis were prospectively included in seven referral centers between 2020 and 2022. Patients with conventional side-to-side anastomosis were enrolled from a previously published cohort. A propensity score analysis was performed to compare recurrence at first endoscopy in a matched 1:2 ratio population. RESULTS: A total of 433 patients with ileocolonic anastomosis were enrolled, of whom 155 had a Kono-S anastomosis. Before matching, both groups were unbalanced for preoperative, intraoperative, and postoperative characteristics. After matching patients with available endoscopic follow-up, endoscopic recurrence ≥i2 was found in 47.5% of the Kono-S group and 44.3% of the conventional side-to-side group (p=0.6745). CONCLUSIONS: The KoCoRICCO study suggests that Kono-S anastomosis does not reduce the risk of endoscopic recurrence in Crohn's disease compared to conventional side-to-side anastomosis. Further research with a longer follow-up is necessary to determine whether there is a potential benefit on surgical recurrence.

KONO-S Anastomosis Is Not Superior to Conventional Anastomosis for the Reduction of Postoperative Endoscopic Recurrence in Crohn's Disease.

BACKGROUND: Surgical resection rates remain high in Crohn's disease (CD). Reducing postoperative recurrence (POR) is challenging. Besides drug therapy, the surgical anastomosis technique may reduce POR. We aimed to compare the endoscopic POR rate after Kono-S vs standard ileocolic anastomosis. METHODS: The study included all consecutive CD patients operated on for ileocolic resection with a Kono-S anastomosis between February 2020 and March 2022. These patients were prospectively followed, and colonoscopy was performed 6 to 12 months after surgery. Patients were compared with a historical cohort of patients operated on with a conventional anastomosis in the same center. The primary end point was endoscopic POR (Rutgeerts score ≥i2). Factors associated with POR were assessed by univariate and multivariable analyses. RESULTS: A total of 85 patients were included, 30 in the Kono-S group and 55 in the control group. At baseline, there was no significant difference between the 2 groups regarding CD characteristics or known POR risk factors, including previous exposure to biologics. At 6 to 12 months, endoscopic POR rate did not differ significantly between groups (56.7% in the Kono-S group vs 49.1% in the control group; P = .50), nor did endoscopic POR according to the modified Rutgeerts score ≥i2b (46.7% in the Kono-S group vs 40% in the control group; P = .55). Severe endoscopic POR rates were 23.3% and 18.2% in each group, respectively. Clinical recurrence rate was similar in both groups, and no recurrent surgery occurred. By multivariable analysis, the type of anastomosis was not associated with endoscopic POR (OR, 1.229; 95% CI, 0.461-3.274, P = .68); however, postoperative treatment with anti-TNF was (OR, 0.337; 95% CI, 0.131-0.865 P = .02). CONCLUSIONS: Kono-S anastomosis was not associated with a reduced rate of endoscopic POR. These results warrant confirmation in prospective, randomized, multicenter studies.

This study aimed to evaluate the role of Kono-S anastomosis in postoperative recurrence (POR), in a prospective cohort of Crohn's disease patients undergoing ileocolic resection with this anastomosis. Results were compared with a historical cohort of patients who were operated on with conventional anastomosis. Endoscopic POR rate did not differ significantly between groups, and the type of anastomosis was not associated with endoscopic POR by multivariable analysis.

Cardiotoxicity is mitigated after a supervised exercise program in HER2-positive breast cancer undergoing adjuvant trastuzumab.

Background: Trastuzumab is used, alone or in conjunction with standard chemotherapy, to treat HER2-positive breast cancer (BC). Although it improves cancer outcomes, trastuzumab. can lead to cardiotoxicity. Physical exercise is a safe and effective supportive therapy in the management of side effects, but the cardioprotective effects of exercise are still unclear. Objectives: The primary aim of this study was to test whether trastuzumab-induced cardiotoxicity [left ventricular ejection fraction (LVEF) under 50%, or an absolute drop in LVEF of 10%] was reduced after a supervised exercise program of 3 months in patients with HER2-positive breast cancer. Secondary endpoints were to evaluate (i) cardiotoxicity rates using other criteria, (ii) cardiac parameters, (iii) cardiorespiratory fitness and (iv) whether a change in LVEF influences the cardiorespiratory fitness. Methods: 89 women were randomized to receive adjuvant trastuzumab in combination with a training program (training group: TG; n = 46) or trastuzumab alone (control group: CG; n = 43). The primary and secondary endpoints were evaluated at the end of the supervised exercise program of 3 months (T3). Results: After exercise program, 90.5 % of TG patients and 81.8% of CG patients did not exhibit cardiotoxicity. Furthermore, whatever the used criterion, percentage of patients without cardiotoxicity were greater in TG (97.6 and 100% respectively) than in CG (90.9 and 93.9% respectively). LVEF and GLS values remained stable in both groups without any difference between the groups. In contrast, at T3, peak VO2 (+2.6 mL.min-1.kg-1; 95%CI, 1.8 to 3.4) and maximal power (+21.3 W; 95%CI, 17.3 to 25.3) increased significantly in TG, whereas they were unchanged in CG (peak VO2: +0.2 mL.min-1.kg-1; 95%CI, -0.5 to 0.9 and maximal power: +0.7 W, 95%CI, -3.6 to 5.1) compared to values measured at T0. No correlation between LVEF changes and peak VO2 or maximal power was observed. Conclusion: A 12-week supervised exercise regimen was safe and improved the cardiopulmonary fitness in particular peak VO2, in HER2-positive BC patients treated with adjuvant trastuzumab therapy. The study is under powered to come to any conclusion regarding the effect on cardiotoxicity. Clinical trial registration: www.ClinicalTrials.gov, identifier: NCT02433067.

Could 18-FDG PET-CT Radiomic Features Predict the Locoregional Progression-Free Survival in Inoperable or Unresectable Oesophageal Cancer?

Background: We evaluated the value of pre-treatment positron-emission tomography−computed tomography (PET-CT)-based radiomic features in predicting the locoregional progression-free survival (LR-PFS) of patients with inoperable or unresectable oesophageal cancer. Material and Methods: Forty-six patients were included and 230 radiomic parameters were extracted. After a principal component analysis (PCA), we identified the more robust radiomic parameters, and we used them to develop a heatmap. Finally, we correlated these radiomic features with LR-PFS. Results: The median follow-up time was 17 months. The two-year LR-PFS and PFS rates were 35.9% (95% CI: 18.9−53.3) and 21.6% (95%CI: 10.0−36.2), respectively. After the correlation analysis, we identified 55 radiomic parameters that were included in the heatmap. According to the results of the hierarchical clustering, we identified two groups of patients presenting statistically different median LR-PFSs (22.8 months vs. 9.9 months; HR = 2.64; 95% CI 0.97−7.15; p = 0.0573). We also identified two radiomic features ("F_rlm_rl_entr_per" and "F_rlm_2_5D_rl_entr") significantly associated with LR-PFS. Patients expressing a "F_rlm_2_5D_rl_entr" of <3.3 had a better median LR- PFS (29.4 months vs. 8.2 months; p = 0.0343). Patients presenting a "F_rlm_rl_entr_per" of <4.7 had a better median LR-PFS (50.4 months vs. 9.9 months; p = 0.0132). Conclusion: We identified two radiomic signatures associated with a lower risk of locoregional relapse after CRT.

Impact of open-label versus blinded study design on patient-reported outcomes data in randomized clinical trials of immunotherapy in advanced or metastatic cancer patients: a systematic review.

AIM: A systematic literature review of immuno-oncology trials was conducted to assess the potential impact of open-label vs double-blind trial design on patient-reported outcome (PRO) data. METHODS: A systematic search of indexed literature published from January 2009 to May 2019 was conducted using PubMed/MEDLINE, Cochrane Library, and EMBASE database. All randomized clinical trials (RCTs) of immuno-oncology therapies on advanced cancer patients reporting PRO data were identified. Descriptive analyses were performed to quantify differences at baseline and over time, by the type of study, regarding questionnaire completion rate and PRO scores. RESULTS: In total, 23 studies were retained (15 open-label, 8 blinded). At baseline, no difference in completion rate was observed between arms irrespective of trial design (absolute mean difference of 2.8% and 2.2% for open label and blinded studies, respectively). No clinically significant difference in baseline PRO scores was observed between arms. Over time, impact on PRO scores could not be identified due to the limited number of studies, heterogeneity of questionnaires and tumor types. CONCLUSIONS: Trial design had no impact on PRO completion rate or baseline scores. Future research should involve analyses by specific cancer types and ideally compare individual data from two similar RCTs (blinded vs. open-label).

Quality of patient-reported outcome reporting according to the CONSORT statement in randomized controlled trials with glioblastoma patients.

BACKGROUND: Randomized controlled trials (RCTs) represent the best evidence in oncology research. Glioblastoma is the most frequent and deadly primary brain tumor, affecting health-related quality of life. An important end point is patient-reported outcomes (PROs). There are no data regarding how well publications of glioblastoma RCTs report PROs. A specific PRO extension of the Consolidated Standards of Reporting Trials (CONSORT) statement was created to improve the quality of reporting. The aim of this study was to evaluate adherence to the CONSORT-PRO statement in reporting RCTs addressing the treatment of patients with glioblastoma. PRO analysis methodology was explored and criteria associated with higher quality of reporting were investigated. METHODS: From PubMed/MEDLINE and the Cochrane Library databases, all phase 2 and 3 RCTs related to glioblastoma published between 1995 and 2018 were reviewed according to the CONSORT-PRO statements. An overall quality score on a 0 to 100 scale was defined based on these criteria and factors associated with this score were identified. RESULTS: Forty-four RCTs were identified as relevant according to predefined criteria. The median overall quality score was 26. No difference was observed regarding reporting quality over the years. CONSORT-PRO items concerning data collection and analysis were poorly reported. Thirty-four trials (77%) used longitudinal data. The most frequent statistical method for PROs analysis was the mean change from baseline (63%). Factors associated with improved overall quality score were the presence of a secondary publication dedicated to PROs results, the statement of any targeted dimensions, and when trials reported results using multiple methods. CONCLUSION: Despite the importance of measuring PROs in patients with glioblastoma, employment of the CONSORT-PRO statement is poor in RCTs.

Feasibility of health-related quality of life (HRQoL) assessment for cancer patients using electronic patient-reported outcome (ePRO) in daily clinical practice.

INTRODUCTION: Routine Electronic Monitoring of Health-Related Quality of Life (HRQoL) (REMOQOL) in clinical care with real-time feedback to physicians could help to enhance patient-centered care. We evaluated the feasibility of REMOQOL in the French context in the QOLIBRY study. The primary objective was to assess the patients' compliance with REMOQOL. METHODS: The QOLIBRY study was a single-center, prospective study conducted in the University Hospital of Besançon (France). Eligible patients were those treated with systemic therapies for breast, lung or colorectal cancer at any stage. Patients were invited to complete the EORTC QLQ-C30 questionnaire and cancer-site-specific modules before each visit on tablets and/or computers in the hospital or at home. During the consultation, physicians had real-time access to visual summaries of HRQoL scores. Compliance was assessed as adequate if at least 66% of HRQoL assessments were completed during the 4 months of follow-up. RESULTS: Between March 2016 and October 2018, 177 patients were included in the QOLIBRY study. Median age was 64 years (IQR 54-71). The proportion of patients with an adequate compliance rate was 95.5% (n = 63) in the breast cancer cohort, 98.2% (n = 55) in the colorectal cancer cohort, and 90.9% (n = 50) in the lung cancer cohort. The physicians checked the HRQoL results in 73.1% of visits and prescribed supportive care and adapted patient management in 8.3% and 5.2% of visits, respectively. CONCLUSION & PERSPECTIVES: The results of QOLIBRY study suggest that REMOQOL is feasible in the French context. However, information about HRQoL monitoring, training of the physicians in the use of the software, and recommendations for using HRQoL results to guide care are essential and must be improved.

Prognostic Value of Tumor Deposits for Disease-Free Survival in Patients With Stage III Colon Cancer: A Post Hoc Analysis of the IDEA France Phase III Trial (PRODIGE-GERCOR).

PATIENTS AND METHODS: A post hoc analysis of all pathologic reports from patients with stage III CC included in the IDEA France phase III study (ClinicalTrials.gov identifier: NCT00958737) investigating the duration of adjuvant fluorouracil, leucovorin, and oxaliplatin or capecitabine and oxaliplatin therapy (3 v 6 months) was performed. The primary objective was to determine the prognostic impact of TD on disease-free survival (DFS). The effect of the addition of TD to LNM count on pN restaging was also evaluated. A multivariable analysis was performed to establish the association between TD and DFS. RESULTS: Of 1,942 patients, 184 (9.5%) had TDs. The pN1a/b and pN1c populations showed similar DFS. TD-positive patients had worse prognosis compared with TD-negative patients, with 3-year DFS rates of 65.6% (95% CI, 58.0% to 72.1%) and 74.7% (95% CI, 72.6% to 76.7%; P = .0079), respectively. On multivariable analysis, TDs were associated with a higher risk of recurrence or death (hazard ratio [HR], 1.36; P = .0201). Other adverse factors included pT4 and/or pN2 disease (HR, 2.21; P < .001), the 3 months of adjuvant treatment (HR, 1.29; P = .0029), tumor obstruction (HR, 1.28; P = .0233), and male sex (HR, 1.24; P = .0151). Patients restaged as having pN2 disease (n = 35, 2.3%) had similar DFS as patients initially classified as pN2. CONCLUSION: The presence of TDs is an independent prognostic factor for DFS in patients with stage III CC. The addition of TD to LNM may help to better define the duration of adjuvant therapy.