Ovary Part 7
Episode Notes
Cytoreduction definitions
Optimal: <1 cm gross residual disease in any location
R0: microscopic/no gross residual disease
Suboptimal: >1 cm gross residual disease in any location
Prediction of Optimal Cytoreduction
Laparoscopy
Fagotti Score, 2008
Describes the ability of laparoscopy to predict optimal cytoreduction
“Predictive Index Value” ranges from 0-14
Score of >=8 associated w/ an inability to optimally cytoreduce
PIV value of 2 given for each of the following:
For peritoneal carcinomatosis with unresectable peritoneal involvement or miliary distribution
For diaphragmatic carcinomatosis with widespread disease, infiltrating or confluent nodules on most of the diaphragm
For mesenteric disease with large infiltrating nodules or involvement of the upper root of the mesentery (for which limited mobility of intestines is a key finding)
For omental disease with tumor diffusely involving up to the greater curvature of the stomach
For bowel infiltration requiring probable need for bowel resection or miliary carcinomatosis on the loops of bowel
For stomach infiltration with obvious involvement of the gastric wall
Lastly, for liver surface metastases with any surface lesion > 2 cm.
Updated Fagotti Score, 2015
Updated the laparoscopic scoring system in the context of now known improved survival with complete resection as opposed to optimal resection, and with the increase in use of upper abdominal surgery
Retraction of the mesentery and miliary carcinomatosis were shown to be invariably associated with unresectable disease, thus their contribution to the score were now excluded
A value of >=10 (out of maximum 12) was found to have a 0% chance of achieving complete resection, and the risk of unnecessary laparotomy was 33%. As such, the authors concluded that with this updated scoring system, a score of >=10 should be strongly considered for triage from primary debulking surgery to neoadjuvant chemotherapy with interval debulking surgery.
Fleming 2018
Evaluation of PFS with use of Fagotti screening
Out of the 215 who were assessed by laparoscopy, 125 patients had a Fagotti score of < 8
R0 resection was achieved in 88% of patients who underwent PDS and in 74% who underwent NACT with IDS
PFSl was best in the PDS w/ R0 resection group (23.5 mo) followed by PDS w/ R1 resection group (17.5 mo). These were followed by NACT with R0 and R1 IDS, with 15.5 mo and 12.9 mo respectively.
Imaging/Labs Combo
Suidan et al. 2014
3 clinical and 6 radiologic criteria to be predictive of suboptimal debulking on multivariate analysis
age ≥60, CA-125 ≥ 500, ASA class 3-4, and 6 radiographic markers: enlarged suprarenal lymph nodes, diffuse small bowel adhesion or thickening, lesions in the small bowel mesentery, lesions in the root of the superior mesenteric artery, lesions in the perisplenic area, and lesions in the lesser sac
Suboptimal debulking was linearly associated with the number of markers a patient had. With ≥9 positive markers, the rate of suboptimal debulking was 74% vs 5% if no preoperative criteria were met.
Patient Factors
Narasimhulu 2019, 2023
Triage algorithm to reduce 90 day surgical morbidity and mortality
High risk if one of the following is met: albumin < 3.5 g/dL, age >= 80, or age 75-79 in addition to ECOG performance status > 1, stage IV disease, or complex surgery likely
If high risk -> triage to NACT (Figure 1. )
Wright 2011, 2012
Surgical morbidity
Greatest among elderly patients who were treated with multiple procedures
composite complication rate rose with age, with a 17% rate seen in patients < 50 years old, and 31% in patients > 80 years
Complications included surgical site complications, medical complications, infectious complications, increased transfusion rates, and prolonged hospitalizations
Treatment Delay
28% of patients experienced some delay in starting chemo if they received surgery first in the treatment paradigm. The extent of cytoreduction was associated with delay in chemotherapy, as were postoperative complications.
Suggested that if the delay from surgery is > 12 weeks, this starts to affect cancer-related outcomes
Secondary Cytoreductive Surgery
Rose 2004
Evaluated secondary cytoreduction after adjuvant therapy for patients who had a suboptimal debulking at time of their initial surgery
3 cycles adjuvant chemo → randomized to secondary surgery right away vs finishing remaining 3 cycles of adjuvant chemo
No difference in PFS or risk of death
Negated the role of secondary cytoreductive surgery in the frontline setting
Chi et al. 2006
Retrospective review of pts w/ PS recurrent EOC
Positive prognostic factors: longer disease free interval, the better
Negative prognostic factors: higher number of sites of recurrence, residual disease at time of secondary cytoreduction
Salani et al., 2007
Retrospective study of 55 patients
Inclusion criteria: complete response to primary therapy, >= 12 months from initial diagnosis and recurrence, <= 5 primary sites
74.5% had complete cytoreduction at secondary surgery
Predictors of improved OS: diagnosis to recurrence interval of >=18 months, limited number of recurrence sites, and lack of residual disease after secondary cytoreduction
No association: Age, tumor grade, histology, CA-125 level, presence of ascites, and tumor size were not associated with survival.
DESKTOP III, 2021
N = 407
Inclusion criteria: first relapse after a platinum-free interval of 6 months and a positive AGO score (complete resection at primary surgery, ECOG 0, ascites < 500 mL)
Stratified by PFI of 6-12 mo vs > 12 mo
Randomized to investigator’s choice chemo vs cytoreductive surgery + chemo
Complete resection was achieved in 75% of patients
Median OS was 53.7 mo vs 46.0 months favoring cytoreductive surgery
Best outcome was seen amongst patients with a complete secondary cytoreduction, with a median OS of 61.9 months
important to note that patients with an incomplete resection actually had an overall survival of 28 months, meaning that incomplete secondary cytoreduction had a survival detriment compared to chemotherapy alone
SOC-1, 2021
N = 357
iMODEL score: international model to predict resectability
Had more disease on average than in DESKTOP III or GOG 213
Complete resection in 77%
PFS 17.4 mo w/ surgery vs 11.9 mo w/o surgery
OS not different
Benefit only seen if R0 resection achieved
GOG 213, 2019
Two separate objectives
Assess the benefit of bevacizumab
Assess the benefit of secondary cytoreductive surgery
N = 485 in surgery arm
randomized to cytoreductive surgery followed by chemotherapy +/- bevacizumab versus chemotherapy +/- bevacizumab alone
Complete resection in 67%
OS and PFS in the surgery + chemo +/- bev vs chemo +/- bev alone arms were not significantly different
Most patients received bevacizumab, which complicates the results in evaluating the utility of secondary cytoreduction
Conte et al. 2023
Evaluated role of MIS secondary cytoreduction
Retrospective review of 62 MIS and 214 open cases
Overall complete resection rate was 95%, no difference between mode of surgery
Factors predictive of successful MIS: NACT at first chemotherapy and single or oligometastatic disease
No significant difference in 3-year post-recurrence survival
Figure 1. Narasimhulu 2019, 2023 (8)
References
1. Suidan RS, Ramirez PT, Sarasohn DM, et al. A multicenter prospective trial evaluating the ability of preoperative computed tomography scan and serum CA-125 to predict suboptimal cytoreduction at primary debulking surgery for advanced ovarian, fallopian tube, and peritoneal cancer ☆. Gynecol Oncol. 2014;134:455-461. doi:10.1016/j.ygyno.2014.07.002
2. Fagotti A, Ferrandina G, Fanfani F, et al. Prospective validation of a laparoscopic predictive model for optimal cytoreduction in advanced ovarian carcinoma. Published online 2008. doi:10.1016/j.ajog.2008.06.052
3. Fagotti A, Ferrandina G, Fanfani F, et al. A Laparoscopy-Based Score To Predict Surgical Outcome in Patients With Advanced Ovarian Carcinoma: A Pilot Study. doi:10.1245/ASO.2006.08.021
4. Fleming ND, Nick AM, Coleman RL, et al. Laparoscopic Surgical Algorithm to Triage the Timing of Tumor Reductive Surgery in Advanced Ovarian Cancer. Obstetrics and Gynecology. 2018;132(3):545-554. doi:10.1097/AOG.0000000000002796
5. Wright JD, Lewin SN, Deutsch I, et al. Defining the limits of radical cytoreductive surgery for ovarian cancer. Gynecol Oncol. 2011;123:467-473. doi:10.1016/j.ygyno.2011.08.027
6. Wright JD, Herzog TJ, Neugut AI, et al. Effect of radical cytoreductive surgery on omission and delay of chemotherapy for advanced-stage ovarian cancer. Obstetrics and Gynecology. 2012;120(4):871-881. doi:10.1097/AOG.0b013e31826981de
7. Narasimhulu DM, Kumar A, Weaver AL, Mcgree ME, Langstraat CL, Cliby WA. Using an evidence-based triage algorithm to reduce 90-day mortality after primary debulking surgery for advanced epithelial ovarian cancer. doi:10.1016/j.ygyno.2019.08.004
8. Narasimhulu DM, Fagotti A, Scambia G, et al. Validation of a risk-based algorithm to reduce poor operative outcomes after complex surgery for ovarian cancer. Int J Gynecol Cancer. 2023;33:83-88. doi:10.1136/ijgc-2022-003799
9. Salani R, Santillan A, Zahurak ML, et al. Secondary cytoreductive surgery for localized, recurrent epithelial ovarian cancer: Analysis of prognostic factors and survival outcome. Cancer. 2007;109(4):685-691. doi:10.1002/cncr.22447
10. Harter P, Bois A Du, Hahmann M, et al. Surgery in Recurrent Ovarian Cancer: The Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) DESKTOP OVAR Trial. doi:10.1245/s10434-006-9058-0
11. Harter P, Sehouli J, Reuss A, et al. Prospective Validation Study of a Predictive Score for Operability of Recurrent Ovarian Cancer: The Multicenter Intergroup Study DESKTOP II. A Project of the AGO Kommission OVAR, AGO Study Group, NOGGO, AGO-Austria, and MITO. International Journal of Gynecologic Cancer. 2011;21(2):289-295. doi:10.1097/IGC.0B013E31820AAAFD
12. Harter P, Sehouli J, Vergote I, et al. Randomized Trial of Cytoreductive Surgery for Relapsed Ovarian Cancer. New England Journal of Medicine. 2021;385(23):2123-2131. doi:10.1056/NEJMOA2103294/SUPPL_FILE/NEJMOA2103294_DATA-SHARING.PDF
13. Coleman RL, Spirtos NM, Enserro D, et al. Secondary Surgical Cytoreduction for Recurrent Ovarian Cancer. New England Journal of Medicine. 2019;381(20):1929-1939. doi:10.1056/nejmoa1902626
14. Shi T, Zhang Y, Yin S, et al. Secondary cytoreduction followed by chemotherapy versus chemotherapy alone in platinum-sensitive relapsed ovarian cancer (SOC-1): a multicentre, open-label, randomised, phase 3 trial. Articles Lancet Oncol. 2021;22:439-488. doi:10.1016/S1470-2045(21)00006-1
15. Rose PG, Nerenstone S, Brady MF, et al. Secondary Surgical Cytoreduction for Advanced Ovarian Carcinoma. New England Journal of Medicine. 2004;351(24):2489-2497. doi:10.1056/NEJMOA041125/ASSET/F0713690-9778-45D7-B35D-85E4E5EFAB4D/ASSETS/IMAGES/LARGE/NEJMOA041125_T2.JPG
16. Chi DS, McCaughty K, Diaz JP, et al. Guidelines and selection criteria for secondary cytoreductive surgery in patients with recurrent, platinum-sensitive epithelial ovarian carcinoma. Cancer. 2006;106(9):1933-1939. doi:10.1002/CNCR.21845
17.Conte C, Marchetti C, Loverro M, et al. Role of minimally invasive secondary cytoreduction in patients with recurrent ovarian cancer Fondazione Policlinico GYNECOLOGICAL CANCER. Int J Gynecol Cancer. 2023;33:137-144. doi:10.1136/ijgc-2022-003904