The article:
Harter P, du Bois A, Hahmann M, et al for the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Committee (AGO OC) and the AGO Ovarian Cancer Study Group (AGO-OVAR). Surgery in recurrent ovarian cancer: the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) DESKTOP OVAR Trial. Ann Surg Oncol 2006;13(12):1702-10.
The reviewer:
Dr James Nicklin is a gynaecological oncologist at the Royal Brisbane and Women’s Hospital in Queensland.
Summary
Abbreviations
Confidence Interval (CI), Descriptive Evaluation of pre-operative Selection KriTeria for OPerability in recurrent OVARian cancer (DESKTOP OVAR), Eastern Cooperative Oncology Group (ECOG), Epithelial Ovarian Cancer (EOC), Gynecologic Oncology Group (GOG), Hazard Ratio (HR), Odds Ratio (OR).
Study Design
A retrospective analysis was performed on hospital records of 267 patients with recurrent EOC who had received cytoreductive surgery between 2000 and 2003 from 25 centres in Germany and Switzerland. The primary outcome of interest was survival. Investigators also wished to determine selection criteria and predictive factors for successful cytoreductive surgery.
Findings
The following three variables had independent impacts on survival (using multivariate analysis):
- Complete resection, residual tumour 0mm vs >0mm (OR: 2.94; 95% CI: 1.68, 5.17; p<0.001)
- Ascites, <500 ml vs ≥500 ml (OR: 2.30; 95% CI: 1.31, 4.04; p=0.004)
- Postoperative chemotherapy, platinum-containing chemotherapy yes vs no (OR: 1.84; 95% CI: 1.13, 3.01; p=0.015)
The following three variables had independent impacts on achieving complete resection (using multivariate analysis):
- Performance status (ECOG), 0 vs >0 (OR: 2.65; 95% CI: 1.56, 4.52; p<0.001)
- Residual disease after primary surgery, 0mm vs >0mm (OR: 2.46; 95% CI: 1.45, 4.20; p<0.001)
- Ascites, <500ml vs ≥500 ml (OR: 5.08; 95% CI: 1.97, 13.16; p<0.001)
Complete resection was associated with significantly longer survival compared with surgery leaving postoperative residuals, median survival 45.2 months compared to 19.7 months respectively (HR: 3.71; 95% CI: 2.27, 6.05; p<0.001). In patients who were not completely debulked, the size of the residual tumour did not impact survival, median survival of patients with residual tumours 1-10mm compared to >10mm were 19.6 and 19.7 months respectively (HR: 0.84; 95% CI: 0.51, 1.40; p=0.502).
Conclusion
The authors concluded that only complete resection was associated with increased survival in recurrent ovarian cancer.
Commentary
What does this article add to existing clinical evidence in this area?
This retrospective multi-institutional study makes some contribution to our understanding of the role of secondary cytoreductive surgery in the management of recurrent epithelial ovarian cancer (EOC). Consistent with prior studies, complete cytoreduction was associated with improved survival. This study, with a population that was by definition largely platinum-sensitive (ie treatment free interval >12 months in 62.9% and >6 months in 86.5%), supports a large number of prior chemotherapy studies which demonstrate that platinum-containing chemotherapy is superior to non-platinum containing chemotherapy as salvage therapy in this circumstance. In contrast to most prior studies which demonstrate that any ascites is a poor prognostic feature, this study shows that ascites <500 mls is associated with improved outcome. The secondary study endpoint of factors prognostic of optimal cytoreduction contributes to the sparse data published to date. The authors found that the variables of performance status, ascites <500 mls and optimal cytoreduction after primary surgery were all independently predictive of an optimal surgical result.
How adequate was the methodology used in addressing the aims of this study?
This is the largest retrospective series published to date involving 267 patients from 25 centres. Consequently, some caution is warranted in interpreting the conclusions. There are likely selection biases in the paper. There are no data about inclusion criteria from participating individual institutions and no data about the proportion and characteristics of patients not offered secondary cytoreductive surgery. Institutions contributed an average of only 10.7 patients over the 4 years of the study, suggesting low volume of clinical material and potentially limited sub-specialty clinical expertise. There is likely heterogeneity in surgical skills.
The authors were not able to test the influence of a residual disease of <5mm on survival. Virtually all studies to date demonstrate a survival advantage for no macroscopic residual disease, but only the largest studies show some value for cytoreduction to <5mm, with no benefit for patients left with ≥ 10mm disease. This is an important consideration because carcinomatosis is a frequent finding at secondary surgery.
Recurrent EOC is rarely curable, so quality of life is of paramount clinical consideration and importance. The methodology of the present study necessarily precluded evaluation of this important endpoint.
What are the implications of this study for clinical practice in Australia?
The present study will reinforce the current standard of practice in Australia. The most robust and clinically important finding of the study was the association between complete surgical cytoreduction and improved survival. Clearly optimal surgical clearance of recurrent disease is the desired objective of secondary surgery.
This trial is the first in a series and was designed to define the surgical endpoint for subsequent prospective trials. The hypothetical model being assessed in AGODESKTOPII will be followed by a randomised trial to compare surgery and chemotherapy versus chemotherapy alone in prospective selected patients as AGODESKTOP III. The Gynecologic Oncology Group (GOG) is about to commence a randomised phase III trial of chemotherapy versus surgery and chemotherapy for patients with recurrent ovarian cancer with a treatment free interval of >6 months (GOG 213). There is evidence that the interval between the end of first line treatment and relapse (treatment free interval) is an important predictor of likelihood of response. We await with interest the results of this study and subsequent AGODESKTOP randomised studies.
Editor: Ms Jane Francis, Program Manager/Ovarian Cancer NBCC
Editorial Committee: Prof Michael Friedlander – Medical Oncologist, Prof Neville Hacker – Gynaecological Oncologist, Dr Gillian Mitchell – Medical Oncologist, Dr Deborah Neesham – Gynaecological Oncologist, Ms Georgie Richter – Gynaecological Nurse
Disclaimer
Clinical Update - Ovarian Cancer is produced by the National Breast Cancer Centre (NBCC) and is intended to provide health professionals with timely expert commentary on new research in ovarian cancer. Commentaries included in Clinical Update - Ovarian Cancer do not replace recommendations included in NBCC clinical practice guidelines.
Information contained in Clinical Update - Ovarian Cancer is not intended to be used as substitute for an independent health professional's advice. The NBCC does not accept any liability for any injury, loss or damage incurred by use of or reliance on the information contained in Clinical Update - Ovarian Cancer. The NBCC develops material based on the best available evidence however cannot guarantee and assumes no legal liability or responsibility for the currency or completeness of the information.
