Does aggressive surgery improve outcomes? Interaction between preoperative disease burden and complex surgery in patients with advanced-stage ovarian cancer: an analysis of GOG 182
Neil S Horowitz, Austin Miller, Bunja Rungruang, Scott D Richard, Noah Rodriguez, Michael A Bookman, Chad A Hamilton, Thomas C Krivak, G Larry Maxwell, Neil S Horowitz, Austin Miller, Bunja Rungruang, Scott D Richard, Noah Rodriguez, Michael A Bookman, Chad A Hamilton, Thomas C Krivak, G Larry Maxwell
Abstract
Purpose: To examine the effects of disease burden, complex surgery, and residual disease (RD) status on progression-free (PFS) and overall survival (OS) in patients with advanced epithelial ovarian cancer (EOC) or primary peritoneal cancer (PPC) and complete surgical resection (R0) or < 1 cm of RD (MR) after surgical cytoreduction.
Patients and methods: Demographic, pathologic, surgical, and outcome data were collected from 2,655 patients with EOC or PPC enrolled onto the Gynecologic Oncology Group 182 study. The effects of disease distribution (disease score [DS]) and complexity of surgery (complexity score [CS]) on PFS and OS were assessed using the Kaplan-Meier method and multivariable regression analysis.
Results: Consistent with existing literature, patients with MR had worse prognosis than R0 patients (PFS, 15 v 29 months; P < .01; OS, 41 v 77 months; P < .01). Patients with the highest preoperative disease burden (DS high) had shorter PFS (15 v 23 or 34 months; P < .01) and OS (40 v 71 or 86 months; P < .01) compared with those with DS moderate or low, respectively. This relationship was maintained in the subset of R0 patients with PFS (18.3 v 33.2 months; DS moderate or low: P < .001) and OS (50.1 v 82.8 months; DS moderate or low: P < .001). After controlling for DS, RD, an interaction term for DS/CS, performance status, age, and cell type, CS was not an independent predictor of either PFS or OS.
Conclusion: In this large multi-institutional sample, initial disease burden remained a significant prognostic indicator despite R0. Complex surgery does not seem to affect survival when accounting for other confounding influences, particularly RD.
Conflict of interest statement
Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.
© 2015 by American Society of Clinical Oncology.
Figures
![Fig 1.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4348639/bin/zlj9991050460001.jpg)
Fig 2.
(A) Progression-free and (B) overall…
Fig 2.
(A) Progression-free and (B) overall survival among low, moderate, and high surgical complexity…
Fig A1.
Determinants of patient outcome; design…
Fig A1.
Determinants of patient outcome; design of multivariable models.
Fig A2.
Patients enrolled onto GOG (Gynecologic…
Fig A2.
Patients enrolled onto GOG (Gynecologic Oncology Group) –182. DS, disease score; MR,
Fig A3.
(A) Progression-free and (B) overall…
Fig A3.
(A) Progression-free and (B) overall survival. MR,
Fig A4.
(A) Progression-free and (B) overall…
Fig A4.
(A) Progression-free and (B) overall survival. CS, complexity score; DS, disease score; MR,…
- Reply to G.D. Aletti et al.Horowitz N, Miller A, Rungruang B, Richard S, Rodriguez N, Bookman MA, Hamilton C, Krivak T, Maxwell GL. Horowitz N, et al. J Clin Oncol. 2015 Oct 20;33(30):3521-2. doi: 10.1200/JCO.2015.62.5707. Epub 2015 Aug 24. J Clin Oncol. 2015. PMID: 26304879 No abstract available.
- There Is Nothing New Under the Sun.Aletti GD, Bristow RE, Chi D, Cliby WA. Aletti GD, et al. J Clin Oncol. 2015 Oct 20;33(30):3520. doi: 10.1200/JCO.2015.61.9536. Epub 2015 Aug 24. J Clin Oncol. 2015. PMID: 26304883 No abstract available.
- Upper abdominal procedures in advanced stage ovarian or primary peritoneal carcinoma patients with minimal or no gross residual disease: an analysis of Gynecologic Oncology Group (GOG) 182.Rodriguez N, Miller A, Richard SD, Rungruang B, Hamilton CA, Bookman MA, Maxwell GL, Horowitz NS, Krivak TC. Rodriguez N, et al. Gynecol Oncol. 2013 Sep;130(3):487-92. doi: 10.1016/j.ygyno.2013.06.017. Epub 2013 Jun 17. Gynecol Oncol. 2013. PMID: 23791702
- Should stage IIIC ovarian cancer be further stratified by intraperitoneal vs. retroperitoneal only disease?: a Gynecologic Oncology Group study.Rungruang B, Miller A, Richard SD, Hamilton CA, Rodriguez N, Bookman MA, Maxwell GL, Krivak TC, Horowitz NS. Rungruang B, et al. Gynecol Oncol. 2012 Jan;124(1):53-8. doi: 10.1016/j.ygyno.2011.09.024. Epub 2011 Oct 26. Gynecol Oncol. 2012. PMID: 22032836 Clinical Trial.
- Neoadjuvant Chemotherapy Increases R0 Cytoreduction Rate But Does Not Improve Final Outcome in Advanced Epithelial Ovarian Cancer.Medina-Franco H, Cortés-González R, Lambreton-Hinojosa F, Fimbres-Morales A, Vargas-Siordia JC. Medina-Franco H, et al. Ann Surg Oncol. 2017 May;24(5):1330-1335. doi: 10.1245/s10434-016-5704-3. Epub 2016 Dec 19. Ann Surg Oncol. 2017. PMID: 27995454
- Optimal primary surgical treatment for advanced epithelial ovarian cancer.Elattar A, Bryant A, Winter-Roach BA, Hatem M, Naik R. Elattar A, et al. Cochrane Database Syst Rev. 2011 Aug 10;2011(8):CD007565. doi: 10.1002/14651858.CD007565.pub2. Cochrane Database Syst Rev. 2011. PMID: 21833960 Free PMC article. Review.
- What is the role of retroperitoneal exploration in optimally debulked stage IIIC epithelial ovarian cancer? An NRG Oncology/Gynecologic Oncology Group ancillary data study.Rungruang BJ, Miller A, Krivak TC, Horowitz NS, Rodriguez N, Hamilton CA, Backes FJ, Carson LF, Friedlander M, Mutch DG, Goodheart MJ, Tewari KS, Wenham RM, Bookman MA, Maxwell GL, Richard SD. Rungruang BJ, et al. Cancer. 2017 May 15;123(6):985-993. doi: 10.1002/cncr.30414. Epub 2016 Nov 16. Cancer. 2017. PMID: 27864921 Free PMC article.
- A three protein signature fails to externally validate as a biomarker to predict surgical outcome in high-grade epithelial ovarian cancer.Hawarden A, Price M, Russell B, Wilson G, Farrelly L, Embleton-Thirsk A, Parmar M, Edmondson R. Hawarden A, et al. PLoS One. 2023 Mar 23;18(3):e0281798. doi: 10.1371/journal.pone.0281798. eCollection 2023. PLoS One. 2023. PMID: 36952534 Free PMC article.
- Cytoreductive Surgery (CRS) and HIPEC for Advanced Ovarian Cancer with Peritoneal Metastases: Italian PSM Oncoteam Evidence and Study Purposes.Marrelli D, Ansaloni L, Federici O, Asero S, Carbone L, Marano L, Baiocchi G, Vaira M, Coccolini F, Di Giorgio A, Framarini M, Gelmini R, Palopoli C, Accarpio F, Fagotti A. Marrelli D, et al. Cancers (Basel). 2022 Dec 6;14(23):6010. doi: 10.3390/cancers14236010. Cancers (Basel). 2022. PMID: 36497490 Free PMC article. Review.
- Near infrared photoimmunotherapy of cancer; possible clinical applications.Wakiyama H, Kato T, Furusawa A, Choyke PL, Kobayashi H. Wakiyama H, et al. Nanophotonics. 2021 May 7;10(12):3135-3151. doi: 10.1515/nanoph-2021-0119. eCollection 2021 Sep. Nanophotonics. 2021. PMID: 36405499 Free PMC article. Review.
- Prognostic influence of an early time to chemotherapy following primary cytoreductive surgery for advanced epithelial ovarian cancer.Eisenkop SM, Okabe H. Eisenkop SM, et al. J Gynecol Oncol. 2022 Nov;33(6):e80. doi: 10.3802/jgo.2022.33.e80. Epub 2022 Sep 8. J Gynecol Oncol. 2022. PMID: 36245229 Free PMC article.
- Ultra-radical (extensive) surgery versus standard surgery for the primary cytoreduction of advanced epithelial ovarian cancer.Hiu S, Bryant A, Gajjar K, Kunonga PT, Naik R. Hiu S, et al. Cochrane Database Syst Rev. 2022 Aug 30;8(8):CD007697. doi: 10.1002/14651858.CD007697.pub3. Cochrane Database Syst Rev. 2022. PMID: 36041232 Review.
- Multicenter Study
- Research Support, N.I.H., Extramural
- Adult
- Aged
- Disease-Free Survival
- Female
- Gynecologic Surgical Procedures*
- Humans
- Kaplan-Meier Estimate
- Middle Aged
- Multivariate Analysis
- Neoplasm, Residual
- Ovarian Neoplasms / surgery*
- Ovarian Neoplasms / therapy
- Peritoneal Neoplasms / surgery*
- Peritoneal Neoplasms / therapy
- Prognosis
- Time Factors
- Treatment Outcome
- Full Text Sources
- Medical
- Miscellaneous
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Fig 2.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4348639/bin/zlj9991050460002.jpg)
![Fig A1.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4348639/bin/zlj9991050460003.jpg)
![Fig A2.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4348639/bin/zlj9991050460004.jpg)
Fig A3.
(A) Progression-free and (B) overall…
Fig A3.
(A) Progression-free and (B) overall survival. MR,
Fig A4.
(A) Progression-free and (B) overall…
Fig A4.
(A) Progression-free and (B) overall survival. CS, complexity score; DS, disease score; MR,…
- Reply to G.D. Aletti et al.Horowitz N, Miller A, Rungruang B, Richard S, Rodriguez N, Bookman MA, Hamilton C, Krivak T, Maxwell GL. Horowitz N, et al. J Clin Oncol. 2015 Oct 20;33(30):3521-2. doi: 10.1200/JCO.2015.62.5707. Epub 2015 Aug 24. J Clin Oncol. 2015. PMID: 26304879 No abstract available.
- There Is Nothing New Under the Sun.Aletti GD, Bristow RE, Chi D, Cliby WA. Aletti GD, et al. J Clin Oncol. 2015 Oct 20;33(30):3520. doi: 10.1200/JCO.2015.61.9536. Epub 2015 Aug 24. J Clin Oncol. 2015. PMID: 26304883 No abstract available.
- Upper abdominal procedures in advanced stage ovarian or primary peritoneal carcinoma patients with minimal or no gross residual disease: an analysis of Gynecologic Oncology Group (GOG) 182.Rodriguez N, Miller A, Richard SD, Rungruang B, Hamilton CA, Bookman MA, Maxwell GL, Horowitz NS, Krivak TC. Rodriguez N, et al. Gynecol Oncol. 2013 Sep;130(3):487-92. doi: 10.1016/j.ygyno.2013.06.017. Epub 2013 Jun 17. Gynecol Oncol. 2013. PMID: 23791702
- Should stage IIIC ovarian cancer be further stratified by intraperitoneal vs. retroperitoneal only disease?: a Gynecologic Oncology Group study.Rungruang B, Miller A, Richard SD, Hamilton CA, Rodriguez N, Bookman MA, Maxwell GL, Krivak TC, Horowitz NS. Rungruang B, et al. Gynecol Oncol. 2012 Jan;124(1):53-8. doi: 10.1016/j.ygyno.2011.09.024. Epub 2011 Oct 26. Gynecol Oncol. 2012. PMID: 22032836 Clinical Trial.
- Neoadjuvant Chemotherapy Increases R0 Cytoreduction Rate But Does Not Improve Final Outcome in Advanced Epithelial Ovarian Cancer.Medina-Franco H, Cortés-González R, Lambreton-Hinojosa F, Fimbres-Morales A, Vargas-Siordia JC. Medina-Franco H, et al. Ann Surg Oncol. 2017 May;24(5):1330-1335. doi: 10.1245/s10434-016-5704-3. Epub 2016 Dec 19. Ann Surg Oncol. 2017. PMID: 27995454
- Optimal primary surgical treatment for advanced epithelial ovarian cancer.Elattar A, Bryant A, Winter-Roach BA, Hatem M, Naik R. Elattar A, et al. Cochrane Database Syst Rev. 2011 Aug 10;2011(8):CD007565. doi: 10.1002/14651858.CD007565.pub2. Cochrane Database Syst Rev. 2011. PMID: 21833960 Free PMC article. Review.
- What is the role of retroperitoneal exploration in optimally debulked stage IIIC epithelial ovarian cancer? An NRG Oncology/Gynecologic Oncology Group ancillary data study.Rungruang BJ, Miller A, Krivak TC, Horowitz NS, Rodriguez N, Hamilton CA, Backes FJ, Carson LF, Friedlander M, Mutch DG, Goodheart MJ, Tewari KS, Wenham RM, Bookman MA, Maxwell GL, Richard SD. Rungruang BJ, et al. Cancer. 2017 May 15;123(6):985-993. doi: 10.1002/cncr.30414. Epub 2016 Nov 16. Cancer. 2017. PMID: 27864921 Free PMC article.
- A three protein signature fails to externally validate as a biomarker to predict surgical outcome in high-grade epithelial ovarian cancer.Hawarden A, Price M, Russell B, Wilson G, Farrelly L, Embleton-Thirsk A, Parmar M, Edmondson R. Hawarden A, et al. PLoS One. 2023 Mar 23;18(3):e0281798. doi: 10.1371/journal.pone.0281798. eCollection 2023. PLoS One. 2023. PMID: 36952534 Free PMC article.
- Cytoreductive Surgery (CRS) and HIPEC for Advanced Ovarian Cancer with Peritoneal Metastases: Italian PSM Oncoteam Evidence and Study Purposes.Marrelli D, Ansaloni L, Federici O, Asero S, Carbone L, Marano L, Baiocchi G, Vaira M, Coccolini F, Di Giorgio A, Framarini M, Gelmini R, Palopoli C, Accarpio F, Fagotti A. Marrelli D, et al. Cancers (Basel). 2022 Dec 6;14(23):6010. doi: 10.3390/cancers14236010. Cancers (Basel). 2022. PMID: 36497490 Free PMC article. Review.
- Near infrared photoimmunotherapy of cancer; possible clinical applications.Wakiyama H, Kato T, Furusawa A, Choyke PL, Kobayashi H. Wakiyama H, et al. Nanophotonics. 2021 May 7;10(12):3135-3151. doi: 10.1515/nanoph-2021-0119. eCollection 2021 Sep. Nanophotonics. 2021. PMID: 36405499 Free PMC article. Review.
- Prognostic influence of an early time to chemotherapy following primary cytoreductive surgery for advanced epithelial ovarian cancer.Eisenkop SM, Okabe H. Eisenkop SM, et al. J Gynecol Oncol. 2022 Nov;33(6):e80. doi: 10.3802/jgo.2022.33.e80. Epub 2022 Sep 8. J Gynecol Oncol. 2022. PMID: 36245229 Free PMC article.
- Ultra-radical (extensive) surgery versus standard surgery for the primary cytoreduction of advanced epithelial ovarian cancer.Hiu S, Bryant A, Gajjar K, Kunonga PT, Naik R. Hiu S, et al. Cochrane Database Syst Rev. 2022 Aug 30;8(8):CD007697. doi: 10.1002/14651858.CD007697.pub3. Cochrane Database Syst Rev. 2022. PMID: 36041232 Review.
- Multicenter Study
- Research Support, N.I.H., Extramural
- Adult
- Aged
- Disease-Free Survival
- Female
- Gynecologic Surgical Procedures*
- Humans
- Kaplan-Meier Estimate
- Middle Aged
- Multivariate Analysis
- Neoplasm, Residual
- Ovarian Neoplasms / surgery*
- Ovarian Neoplasms / therapy
- Peritoneal Neoplasms / surgery*
- Peritoneal Neoplasms / therapy
- Prognosis
- Time Factors
- Treatment Outcome
- Full Text Sources
- Medical
- Miscellaneous
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Fig A3.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4348639/bin/zlj9991050460005.jpg)
Fig A4.
(A) Progression-free and (B) overall…
Fig A4.
(A) Progression-free and (B) overall survival. CS, complexity score; DS, disease score; MR,…
- Reply to G.D. Aletti et al.Horowitz N, Miller A, Rungruang B, Richard S, Rodriguez N, Bookman MA, Hamilton C, Krivak T, Maxwell GL. Horowitz N, et al. J Clin Oncol. 2015 Oct 20;33(30):3521-2. doi: 10.1200/JCO.2015.62.5707. Epub 2015 Aug 24. J Clin Oncol. 2015. PMID: 26304879 No abstract available.
- There Is Nothing New Under the Sun.Aletti GD, Bristow RE, Chi D, Cliby WA. Aletti GD, et al. J Clin Oncol. 2015 Oct 20;33(30):3520. doi: 10.1200/JCO.2015.61.9536. Epub 2015 Aug 24. J Clin Oncol. 2015. PMID: 26304883 No abstract available.
- Upper abdominal procedures in advanced stage ovarian or primary peritoneal carcinoma patients with minimal or no gross residual disease: an analysis of Gynecologic Oncology Group (GOG) 182.Rodriguez N, Miller A, Richard SD, Rungruang B, Hamilton CA, Bookman MA, Maxwell GL, Horowitz NS, Krivak TC. Rodriguez N, et al. Gynecol Oncol. 2013 Sep;130(3):487-92. doi: 10.1016/j.ygyno.2013.06.017. Epub 2013 Jun 17. Gynecol Oncol. 2013. PMID: 23791702
- Should stage IIIC ovarian cancer be further stratified by intraperitoneal vs. retroperitoneal only disease?: a Gynecologic Oncology Group study.Rungruang B, Miller A, Richard SD, Hamilton CA, Rodriguez N, Bookman MA, Maxwell GL, Krivak TC, Horowitz NS. Rungruang B, et al. Gynecol Oncol. 2012 Jan;124(1):53-8. doi: 10.1016/j.ygyno.2011.09.024. Epub 2011 Oct 26. Gynecol Oncol. 2012. PMID: 22032836 Clinical Trial.
- Neoadjuvant Chemotherapy Increases R0 Cytoreduction Rate But Does Not Improve Final Outcome in Advanced Epithelial Ovarian Cancer.Medina-Franco H, Cortés-González R, Lambreton-Hinojosa F, Fimbres-Morales A, Vargas-Siordia JC. Medina-Franco H, et al. Ann Surg Oncol. 2017 May;24(5):1330-1335. doi: 10.1245/s10434-016-5704-3. Epub 2016 Dec 19. Ann Surg Oncol. 2017. PMID: 27995454
- Optimal primary surgical treatment for advanced epithelial ovarian cancer.Elattar A, Bryant A, Winter-Roach BA, Hatem M, Naik R. Elattar A, et al. Cochrane Database Syst Rev. 2011 Aug 10;2011(8):CD007565. doi: 10.1002/14651858.CD007565.pub2. Cochrane Database Syst Rev. 2011. PMID: 21833960 Free PMC article. Review.
- What is the role of retroperitoneal exploration in optimally debulked stage IIIC epithelial ovarian cancer? An NRG Oncology/Gynecologic Oncology Group ancillary data study.Rungruang BJ, Miller A, Krivak TC, Horowitz NS, Rodriguez N, Hamilton CA, Backes FJ, Carson LF, Friedlander M, Mutch DG, Goodheart MJ, Tewari KS, Wenham RM, Bookman MA, Maxwell GL, Richard SD. Rungruang BJ, et al. Cancer. 2017 May 15;123(6):985-993. doi: 10.1002/cncr.30414. Epub 2016 Nov 16. Cancer. 2017. PMID: 27864921 Free PMC article.
- A three protein signature fails to externally validate as a biomarker to predict surgical outcome in high-grade epithelial ovarian cancer.Hawarden A, Price M, Russell B, Wilson G, Farrelly L, Embleton-Thirsk A, Parmar M, Edmondson R. Hawarden A, et al. PLoS One. 2023 Mar 23;18(3):e0281798. doi: 10.1371/journal.pone.0281798. eCollection 2023. PLoS One. 2023. PMID: 36952534 Free PMC article.
- Cytoreductive Surgery (CRS) and HIPEC for Advanced Ovarian Cancer with Peritoneal Metastases: Italian PSM Oncoteam Evidence and Study Purposes.Marrelli D, Ansaloni L, Federici O, Asero S, Carbone L, Marano L, Baiocchi G, Vaira M, Coccolini F, Di Giorgio A, Framarini M, Gelmini R, Palopoli C, Accarpio F, Fagotti A. Marrelli D, et al. Cancers (Basel). 2022 Dec 6;14(23):6010. doi: 10.3390/cancers14236010. Cancers (Basel). 2022. PMID: 36497490 Free PMC article. Review.
- Near infrared photoimmunotherapy of cancer; possible clinical applications.Wakiyama H, Kato T, Furusawa A, Choyke PL, Kobayashi H. Wakiyama H, et al. Nanophotonics. 2021 May 7;10(12):3135-3151. doi: 10.1515/nanoph-2021-0119. eCollection 2021 Sep. Nanophotonics. 2021. PMID: 36405499 Free PMC article. Review.
- Prognostic influence of an early time to chemotherapy following primary cytoreductive surgery for advanced epithelial ovarian cancer.Eisenkop SM, Okabe H. Eisenkop SM, et al. J Gynecol Oncol. 2022 Nov;33(6):e80. doi: 10.3802/jgo.2022.33.e80. Epub 2022 Sep 8. J Gynecol Oncol. 2022. PMID: 36245229 Free PMC article.
- Ultra-radical (extensive) surgery versus standard surgery for the primary cytoreduction of advanced epithelial ovarian cancer.Hiu S, Bryant A, Gajjar K, Kunonga PT, Naik R. Hiu S, et al. Cochrane Database Syst Rev. 2022 Aug 30;8(8):CD007697. doi: 10.1002/14651858.CD007697.pub3. Cochrane Database Syst Rev. 2022. PMID: 36041232 Review.
- Multicenter Study
- Research Support, N.I.H., Extramural
- Adult
- Aged
- Disease-Free Survival
- Female
- Gynecologic Surgical Procedures*
- Humans
- Kaplan-Meier Estimate
- Middle Aged
- Multivariate Analysis
- Neoplasm, Residual
- Ovarian Neoplasms / surgery*
- Ovarian Neoplasms / therapy
- Peritoneal Neoplasms / surgery*
- Peritoneal Neoplasms / therapy
- Prognosis
- Time Factors
- Treatment Outcome
- Full Text Sources
- Medical
- Miscellaneous
![Fig A4.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4348639/bin/zlj9991050460006.jpg)
Source: PubMed