Pattern of and reason for postoperative residual disease in patients with advanced ovarian cancer following upfront radical debulking surgery

ObjectiveThe role of lymphadenectomy in interval debulking surgery (IDS) performed after neoadjuvant chemotherapy (NACT) in advanced ovarian cancer remains unclear. We aimed to investigate the clinical significance of lymphadenectomy in IDS.MethodsWe retrospectively reviewed and analyzed the data of patients with advanced ovarian cancer who underwent NACT followed by IDS.ResultsIn 303 patients receiving NACT-IDS, lymphadenectomy was performed in 127 (41.9%) patients. One hundred and sixty-three (53.8%) patients achieved no gross residual disease (NGRD), and 69 (22.8%) had residual disease < 1 cm, whereas 71 (23.4%) had residual disease ≥ 1cm. No significant difference in progression-free survival (PFS) and overall survival (OS) was observed between the lymphadenectomy group and the no lymphadenectomy group in patients with NGRD, residual disease < 1 cm, and residual disease ≥ 1 cm, respectively. The proportions of pelvic, para-aortic and distant lymph node recurrence were 7.9% (10/127), 4.7% (6/127) and 5.5% (7/127) in the lymphadenectomy group, compared with 5.7% (10/176, P = 0.448), 4.5% (8/176, P = 0.942) and 5.1% (9/176, P = 0.878), respectively, in no lymphadenectomy group. Multivariate analysis identified residual disease ≥ 1 cm [hazard ratios (HR), 4.094; P = 0.008] and elevated CA125 levels after 3 cycles of adjuvant chemotherapy (HR, 2.883; P = 0.004) were negative predictors for OS.ConclusionLymphadenectomy may have no therapeutic value in patients with advanced ovarian cancer underwent NACT-IDS. Our findings may help to better the therapeutic strategy for advanced ovarian cancer. More clinical trials are warranted to further clarify the real role of lymphadenectomy in IDS.

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Primary Surgery or Neoadjuvant Chemotherapy in Advanced Ovarian Cancer: The Debate Continues…

American Society of Clinical Oncology Educational Book ◽

10.1200/edbk_160624 ◽

2016 ◽

pp. 153-162 ◽

Cited By ~ 2

Author(s):

Renee Cowan ◽

Dennis Chi ◽

Sean Kehoe ◽

Matthew Nankivell ◽

Alexandra Leary

Keyword(s):

Ovarian Cancer ◽

Neoadjuvant Chemotherapy ◽

Residual Disease ◽

Tumor Biology ◽

Advanced Ovarian Cancer ◽

Debulking Surgery ◽

Primary Debulking Surgery ◽

Platinum Based Chemotherapy ◽

Patient Reported ◽

The Impact

Primary debulking surgery (PDS) followed by platinum-based chemotherapy has been the cornerstone of treatment for advanced ovarian cancer for decades. Primary debulking surgery has been repeatedly identified as one of the key factors in improving survival in patients with advanced ovarian cancer, especially when minimal or no residual disease is left behind. Achieving these results sometimes requires extensive abdominal and pelvic surgical procedures and consultation with other surgical teams. Some clinicians who propose a primary chemotherapy approach reported an increased likelihood of leaving no macroscopic disease after surgery and improved patient-reported outcomes and quality-of-life (QOL) measures. Given the ongoing debate regarding the relative benefit of PDS versus neoadjuvant chemotherapy (NACT), tumor biology may aid in patient selection for each approach. Neoadjuvant chemotherapy offers the opportunity for in vivo chemosensitivity testing. Studies are needed to determine the best way to evaluate the impact of NACT in each individual patient with advanced ovarian cancer. Indeed, the biggest utility of NACT may be in research, where this approach provides the opportunity for the investigation of predictive markers, mechanisms of resistance, and a forum to test novel therapies.

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Primary debulking surgery (PDS) for stage IIIc ovarian cancer: Quo vadis?

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e15568 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e15568-e15568

Author(s):

Leslie A. Garrett ◽

Whitfield Board Growdon ◽

David M. Boruta ◽

Marcela G del Carmen ◽

Anna M. Priebe ◽

...

Keyword(s):

Ovarian Cancer ◽

Residual Disease ◽

Tumor Biology ◽

Advanced Ovarian Cancer ◽

High Volume ◽

Tumor Board ◽

Debulking Surgery ◽

Stage Iiic ◽

En Bloc ◽

Quo Vadis

e15568 Background: The efficacy of PDS for advanced ovarian cancer has recently been challenged by data suggesting equivalent clinical outcomes for neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS). The strongest known predictor of prolonged survival in either group is the ability to achieve complete resection (CR) to no residual disease. PDS that results in a CR is associated with the longest overall survival of any sequence of treatment. The aim of this study was to determine what type of surgical approach is required to successfully perform PDS. Methods: All women with newly diagnosed stage IIIC epithelial ovarian carcinoma treated at our institution from 2000 to 2010 were identified. Pathology was prospectively reviewed by a faculty gynecologic pathologist. Treatment planning was discussed and documented at our weekly multidisciplinary tumor board conference. Data was retrospectively extracted from computerized medical records. Results: 344 (86%) of 401 women underwent PDS. Optimal debulking was achieved in 278 patients (81%): 35% had CR while 46% had 0.1-1.0 cm residual disease. 56 stage IIIC pts (19%) had a suboptimal surgical outcome with ≥ 1.0 cm. Compared to those having a CR, patients with 0.1-1.0 cm residual were more likely to require splenectomy (17 v 5%; P = 0.002) and transverse colectomy (19 v 10%; P = 0.042), with comparable rates of rectosigmoid resection (41 v 39%; P = 0.712) and en bloc pelvic resection including total peritonectomy (26 v 30%; P = 0.050). Patients undergoing CR were more likely to have diaphragmatic surgery (31 v 20; P = 0.068) and lymphadenectomy (67 v 33%; P < 0.001). Conclusions: PDS is the preferred treatment of stage IIIC epithelial ovarian cancer at high-volume centers demonstrating >75% rates of optimal cytoreduction. Tumor biology may lead to the need for more aggressive upper abdominal procedures in patients with 0.1-1.0 residual. Diaphragm resection, stripping or ablation is more often required in order to achieve CR. Since subclinical macroscopic nodal metastases are often present, lymphadenectomy is also frequently performed to ensure that all possible disease has been resected.

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Advanced ovarian cancer: Is residual disease after debulking surgery affected by genetics factors involved in angiogenesis and immunity pathways?

Annals of Oncology ◽

10.1093/annonc/mdz250.023 ◽

2019 ◽

Vol 30 ◽

pp. v414-v415

Author(s):

M. Bartoletti ◽

S. Gagno ◽

E. Poletto ◽

M. Garziera ◽

S. Scalone ◽

...

Keyword(s):

Ovarian Cancer ◽

Residual Disease ◽

Advanced Ovarian Cancer ◽

Debulking Surgery

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Use and Effectiveness of Neoadjuvant Chemotherapy for Treatment of Ovarian Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2016.68.1239 ◽

2016 ◽

Vol 34 (32) ◽

pp. 3854-3863 ◽

Cited By ~ 67

Author(s):

Larissa A. Meyer ◽

Angel M. Cronin ◽

Charlotte C. Sun ◽

Kristin Bixel ◽

Michael A. Bookman ◽

...

Keyword(s):

Ovarian Cancer ◽

Neoadjuvant Chemotherapy ◽

Observational Study ◽

Residual Disease ◽

Advanced Ovarian Cancer ◽

Stage Iv ◽

Matched Sample ◽

Stage Iiic ◽

Stage Iv Disease ◽

Postoperative Residual

Purpose In 2010, a randomized clinical trial demonstrated noninferior survival for patients with advanced ovarian cancer who were treated with neoadjuvant chemotherapy (NACT) compared with primary cytoreductive surgery (PCS). We examined the use and effectiveness of NACT in clinical practice. Patients and Methods A multi-institutional observational study of 1,538 women with stages IIIC to IV ovarian cancer who were treated at six National Cancer Institute–designated cancer centers. We examined NACT use in patients who were diagnosed between 2003 and 2012 (N = 1,538) and compared overall survival (OS), morbidity, and postoperative residual disease in a propensity-score matched sample of patients (N = 594). Results NACT use increased from 16% during 2003 to 2010 to 34% during 2011 to 2012 in stage IIIC disease ( Ptrend < .001), and from 41% to 62% in stage IV disease ( Ptrend < .001). Adoption of NACT varied by institution, from 8% to 30% for stage IIIC disease (P < .001) and from 27% to 61% ( P = .007) for stage IV disease during this time period. In the matched sample, NACT was associated with shorter OS in stage IIIC disease (median OS: 33 v 43 months; hazard ratio [HR], 1.40; 95% CI, 1.11 to 1.77) compared with PCS, but not stage IV disease (median OS: 31 v 36 months; HR, 1.16; 95% CI, 0.89 to 1.52). Patients with stages IIIC and IV disease who received NACT were less likely to have ≥ 1 cm postoperative residual disease, an intensive care unit admission, or a rehospitalization (all P ≤ .04) compared with those who received PCS treatment. However, among women with stage IIIC disease who achieved microscopic or ≤ 1 cm postoperative residual disease, NACT was associated with decreased OS (HR, 1.49; 95% CI, 1.01 to 2.18; P = .04). Conclusion Use of NACT increased significantly between 2003 and 2012. In this observational study, PCS was associated with increased survival in stage IIIC, but not stage IV disease. Future studies should prospectively consider the efficacy of NACT by extent of residual disease in unselected patients.

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Pazopanib (Paz) monotherapy in Asian women who have not progressed after first-line chemotherapy for advanced ovarian, Fallopian tube, or primary peritoneal carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.5512 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 5512-5512 ◽

Cited By ~ 2

Author(s):

Rongyu Zang ◽

Lingying Wu ◽

Jianqing Zhu ◽

Beihua Kong ◽

Byoung-Gie Kim ◽

...

Keyword(s):

Ovarian Cancer ◽

Fallopian Tube ◽

Residual Disease ◽

Advanced Ovarian Cancer ◽

Figo Stage ◽

Small Sample ◽

Stage Ii ◽

Ca 125 ◽

Asian Women ◽

Debulking Surgery

5512 Background: Paz, an oral multikinase inhibitor of VEGF, PDGF and c-Kit has showed activity in advanced ovarian cancer. This study evaluated paz as maintenance therapy in Asian women with advanced ovarian cancer. Methods: Subjects with FIGO stage II, III, or IV ovarian, fallopian tube, or primary peritoneal cancer whose disease had not progressed after debulking surgery and followed by chemotherapy were randomized 1:1 to paz 800 mg once daily or placebo for up to 24 months. Primary endpoint was PFS by RECIST v1.0 based on visit date. If a progression occurred between the 2 scheduled visits (6 mos apart), progression was considered to have occurred at the next scheduled scan date. This minimized potential bias due to any imbalance of visit frequency between the arms. Results: 145 Asian subjects were randomized; 144 were treated. Mean age was 52.9 years. At diagnosis 17% were FIGO stage II, 73% stage III and 10% stage IV. After debulking surgery, 30% (n = 44) had no residual disease and 41% (n = 59) had. 47% (28/59) had residual disease ≤1cm. Prior to randomization, all subjects received median 8 cycles of chemotherapy; all subjects received platinum and taxane. At randomization 81% had ECOG status 0, 97% were disease free and all had normal CA-125. At clinical data cut-off median PFS was 18.1 months in both arms. Because of the small sample size a HR was not calculated but the KM curves indicated a trend in favor of paz from 6 to 18 mos; the curves crossed after 18 mos. The adverse event (AE) profile for paz was similar to previous reports except rates of hypertension and neutropenia were higher. The most frequent AEs (≥ 20%) on the paz arm were hypertension (76%), neutropenia (64%), leucopenia (53%), diarrhea (47%), hair color changes (40%), palm-plantar erythrodysaethesia syndrome (29%), ALT increase (28%), thrombocytopenia (24%), AST increase (22%) and TSH increase (21%). Most of these AEs were Grade 1-2. Conclusions: The results of this study alone cannot confirm the efficacy of paz maintenance treatment in Asian women with ovarian cancer, but should be interpreted in conjunction of AGO-OVAR16 study. Clinical trial information: NCT01227928.

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Choosing the right timing for interval debulking surgery and perioperative chemotherapy may improve the prognosis of advanced epithelial ovarian cancer: a retrospective study

Journal of Ovarian Research ◽

10.1186/s13048-021-00801-4 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Dengfeng Wang ◽

Guonan Zhang ◽

Chunrong Peng ◽

Yu Shi ◽

Xunwei Shi

Keyword(s):

Ovarian Cancer ◽

Prognostic Factors ◽

Retrospective Study ◽

Cancer Patients ◽

Residual Disease ◽

Advanced Ovarian Cancer ◽

Figo Stage ◽

Postoperative Chemotherapy ◽

Debulking Surgery ◽

Interval Debulking Surgery

Abstract Background Primary debulking surgery (PDS) is the main treatment for patients with advanced ovarian cancer, and neoadjuvant chemotherapy (NACT) is for bulky stage III-IV patients who are poor surgical candidates and/or for whom there is a low likelihood of optimal cytoreduction. NACT can increase the rate of complete cytoreduction, but this advantage has not translated to an improvement in survival. Therefore, we aimed to identify factors associated with the survival of patients who received NACT followed by interval debulking surgery (IDS). Methods A retrospective study was conducted in FIGO stage IIIC-IV epithelial ovarian cancer patients who underwent PDS or IDS in our center between January 1st, 2013, and December 31st, 2018. Results A total of 273 cases were included, of whom 20 were lost to follow-up. Progression-free survival (PFS) and overall survival (OS) of the IDS and PDS groups were found to be similar, although the proportion of patients in stage IV and serum carbohydrate antigen 125 (CA125) levels before treatment in the IDS group were significantly higher than that in the PDS group. Body mass index (BMI), CA125 level before IDS, residual disease after surgery, and the interval between preoperative and postoperative chemotherapy were all found to be independent prognostic factors for PFS; FIGO stage, residual disease after surgery, and CA125 level before IDS were independent prognostic factors for OS. We found that PFS and OS were both significantly longer in patients with normal CA125 levels before IDS and when the interval between preoperative and postoperative chemotherapy was < 35.5 days (IDS-3 group) than for patients in the PDS group. Conclusions The results suggested the importance of timely IDS and postoperative chemotherapy and potentially allowed the identification of patients who would benefit the most from NACT. Normal CA125 levels before IDS and an interval between preoperative and postoperative chemotherapy no longer than 5 weeks were associated with improved prognosis in advanced ovarian cancer patients.

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The surgical outcomes and perioperative complications of bowel resection as part of debulking surgery of advanced ovarian cancer patients.

10.21203/rs.3.rs-21911/v1 ◽

2020 ◽

Author(s):

Shuang Ye ◽

Yiyong Wang ◽

Lei Chen ◽

Xiaohua Wu ◽

Huijuan Yang ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Bowel Resection ◽

Residual Disease ◽

Advanced Ovarian Cancer ◽

Anastomosis Group ◽

Perioperative Outcomes ◽

Morbidity Rate ◽

Debulking Surgery ◽

Resection And Anastomosis

Abstract Background: To review the utilization and perioperative outcomes of bowel resection during cytoreduction of ovarian cancer patients in our institution. Methods: All the patients who received bowel resection including anastomosis and ostomy formation between 2006/01 and 2018/12 were identified. Clinicopathological information was abstracted from the medical records. Postoperative morbidities were assessed according to Clavien-Dindo classification (CDC).Results: There were 182 patients in the anastomosis group and 100 patients in the ostomy group, leading to a total of 282 patients. The median age was 57 years and most patients had high-grade serous histology (88.7%). 49 (17.3%) patients received neoadjuvant chemotherapy. During operation, 78.7% patients had ascites and the median volume was 800 mL. Extensive bowel resection (at least two-segment) and upper abdominal operation was performed in 29 (10.2%) and 69 (24.4%) patients, respectively. Rectosigmoid colon was the most commonly resected (83.8%), followed by right hemicolectomy (5.9%) and small bowel resection (2.8%). No macroscopic residual disease was observed in 42.9% of the patients, while 87.9% of had residual disease ≤1 cm. For the entire cohort, 19.9% (56/282) experienced different complications, not including anastomotic leak (AL). Severe complications (CDC 3-5) accounted for 7.8%, mostly pleural effusion requiring drainage (3.5%), and followed by wound dehiscence requiring delayed repair in operation room (1.8%). Nine patients experienced AL: one in the ostomy group with extensive bowel resection and eight in the anastomosis group. The overall AL rate was 4.2% (9/212) per anastomosis. The AL rate per anastomosis was quite comparable in different populations: 4.4% (patients in the anastomosis group), 4.3% (patients with one-segment bowel resection and anastomosis), 4.0% (patients with extensive bowel resection and anastomosis) and 5.0% (patients with isolated rectosigmoid resection and anastomosis).Conclusions: Execution of bowel resection as part of debulking surgery of patients with newly diagnosed ovarian cancer resulted in an acceptable morbidity rate.

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