Prognostic role and predictors of complete pathologic response to neoadjuvant chemotherapy in primary unresectable ovarian cancer

doi:10.1016/j.ajog.2014.06.034

American Journal of Obstetrics and Gynecology

Volume 211, Issue 6, December 2014, Pages 632.e1-632.e8

https://doi.org/10.1016/j.ajog.2014.06.034 Get rights and content

Objective

The objective of the study was to analyze in a large series of unresectable advanced ovarian cancer (AOC) patients the prognostic role of pathological response to neoadjuvant chemotherapy (NACT).

Study Design

We retrospectively evaluated 322 unresectable AOC patients treated with NACT followed by interval debulking surgery (IDS). Pathological response was classified as follows: complete (cPR) in the absence of residual disease, microscopic (microPR) in the presence of microscopic tumor foci (maximum diameter ≤3 mm), and macroscopic (macroPR) when macroscopic residual disease was detected.

Results

cPR was observed in 21 (6.5%), microPR in 104 (32.3%), and macroPR in 197 (61.2%) patients. No differences were observed in the distribution of baseline clinicopathological characteristics between the groups. Median progression-free survival was 36 months in cPR, 16 in microPR, and 13 in macroPR (P = .001). Median overall survival was 72 months in cPR, 38 in microPR, and 29 in macroPR (P = .018). The survival differences between microPR and macroPR patients were not confirmed when the analysis included only cases resected to no gross residual disease at IDS. cPR retained the independent prognostic role in the multivariate analysis. International Federation of Gynecology and Obstetrics stage IV was the only negative independent predictor of cPR (χ² = 5.362, P = .021).

Conclusion

cPR is an uncommon event in AOC patients receiving NACT and is associated with a longer progression-free survival and overall survival compared with women showing no cPR, even in patients receiving IDS with no gross residual disease. The proposed classification of pathological response may serve in the next future as an easily assessable and highly valuable prognostic tool in this clinical setting.

Section snippets

Materials and Methods

Data for the current analysis were retrieved from the electronic database of our Gynecologic Oncology Unit. Patients’ demographics, medical, surgical, and follow-up data were prospectively collected and retrospectively analyzed.

Results

The clinical-pathological characteristics of the whole series have been summarized in Table 1. cPR to NACT was observed in 21 cases accounting for 6.5% of all women treated with NACT. On the other hand, microPR was documented in 104 women (32.3%), with the remaining 197 patients (61.2%) showing macroscopic residual disease at the time of IDS. International Federation of Gynecology and Obstetrics (FIGO) stage IV was due to the presence of pleural effusion in 37 cases (52.1%) and metastasis in

Comment

The prognostic relevance of pathological response to neoadjuvant treatments has been well established in several unresectable human malignancies including breast, cervical, rectal, and lung cancer so that, in these cancers, the complete disappearance of all neoplastic foci is considered one of the main goals to be pursued by preoperative therapeutic approaches.15, 16, 17, 18

Focusing on AOC, it has been recently reported that the presence of histologically assessed residual disease larger than 1

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Cited by (67)

Interval debulking surgery after neoadjuvant chemotherapy in advanced ovarian cancer - retrospective study comparing surgery after 3 cycles or more of chemotherapy
2022, Journal of Gynecology Obstetrics and Human Reproduction
To evaluate and compare overall survival and progression-free survival in two groups of patients with advanced ovarian cancer, managed by neoadjuvant chemotherapy (3 cycles or more) followed by interval debulking surgery. Secondary objectives regarded surgical morbidity and extent of cytoreduction.
We conducted a retrospective study, in a referral center, evaluating the management of patients diagnosed with advanced ovarian cancer (FIGO IIIC-IV) beneficiating of interval surgery after neoadjuvant chemotherapy. We compared two groups, one in which patients underwent 3 cycles of chemotherapy before surgery, and a second group in which patients underwent more than 3 cycles.
140 patients underwent interval surgery after neoadjuvant chemotherapy. Among these patients, 45 patients underwent 3 or less cycles (group 1) and 95 patients more than 3 cycles (group 2). There was no statistical difference for overall and progression free survival. The mean overall survival was 58,4 months for group 1 and 58,3 for group 2 (p.value = 0.56). The mean progression free survival was 30,5 months for group 1 and 23,8 months for group 2 (p.value = 0.17). More posterior pelvectomies were realized in group 1 compared to group 2 with a statistically significant difference (p=0,01). There was no difference regarding complete macroscopic difference during the surgery between the 2 groups (p=0,09).
Debulking surgery is an invasive and heavy procedure and is not always possible in first line. Neoadjuvant chemotherapy followed by interval debulking surgery is an accepted alternative. The number of administered cycles is questionable, and does not seem to have a significant impact on overall survival and progression free survival. However, surgical morbidity is significantly reduced by increased cycles of chemotherapy.
Clinical analysis of pathologic complete responders in advanced-stage ovarian cancer
2022, Gynecologic Oncology
To determine the clinical characteristics of patients who attained pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) and to identify specific predictive or prognostic factors associated with pCR.
Two distinct populations of patients who underwent NACT followed by interval tumor reductive surgery (TRS) were used in this retrospective study. The first contained 472 patients from a single institution. The second contained only pCR patients (67); those identified from population one, plus 44 obtained through collaborative institutions. Cox analysis and log-rank tests were performed to assess associations between clinical characteristics and pCR outcome, recurrence-free survival (RFS), and overall survival (OS).
The median RFS and OS in our pCR-only population was 24.2 and 80.8 months, respectively, with a median follow-up time of 32.4 months. In our single institution population, 23 patients attained pCR (4.9%) and had longer RFS compared to non-pCR patients with viable microscopic, optimal, or suboptimal residual disease (24.3 vs. 12.1 vs. 11.6 vs. 9.6 months, p = 0.025, 0.012, 0.008, respectively), and longer OS compared to those with optimal or suboptimal residual disease (54.5 vs. 29.4 vs. 25.7 months, p = 0.027, 0.007, respectively). Patients were more than three-fold likely to attain pCR if their CA125 value was normal at the time of surgery (OR 3.54, 95% CI: 1.14–11.05, p = 0.029).
Women with pCR after NACT have significantly longer RFS compared to those with residual viable tumor at the time of interval tumor-reductive surgery, and CA125 is plausible biomarker for identifying these extreme responders preoperatively.
A novel treatment protocol with 6 cycles of neoadjuvant chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in stage III primary ovarian cancer
2021, Surgical Oncology
Citation Excerpt :
The survival analysis of our series confirmed PCI, FIGO stage and CC score as significant prognostic factors. The rate of complete pathological response to NAC (16.7%) is high when compared with other reports [37,38], but, interestingly, it is similar to other studies which adopted 6 cycles in the treatment protocol [33]. In such group of patients we observed the highest 5-year survival rate (78%).
Few prospective studies investigated neoadjuvant chemotherapy (NAC), interval cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in advanced ovarian cancer. We report the results of a phase II study where 6 rather than 3 cycles of NAC, followed by CRS and HIPEC, were adopted (HIPEC_ovaio, EudraCT number 2007-005674-31).
Between 2007 and 2014, 56 patients with stage III primary ovarian cancer and peritoneal carcinomatosis were assigned to 6 cycles of platinum and taxane-based NAC. Of these, two had progression, 8 underwent palliative surgery, and 46 had CRS and HIPEC.
A complete pathological response was observed in 9 patients. Of 46 patients who completed the treatment protocol, 29 had no macroscopic residual tumor. Postoperative grade III morbidity rate was 28.2%; no grade IV complications or mortality events were observed. Five-year overall survival (OS) of the entire series was 36 ± 7% (median: 36, 95% CI: 26–45 months). In 46 patients treated by CRS and HIPEC, 5-year OS was 42 ± 8% (median: 53, 95% CI: 29–76 months), and 5-year progression-free survival was 26 ± 7% (median: 23, 95% CI: 19–27 months). Completeness of cytoreduction, peritoneal cancer index and FIGO stage resulted as significant prognostic factors.
A novel protocol consisting of 6 cycles of NAC, followed by CRS and HIPEC, is associated with notable improvement in peritoneal carcinomatosis, limited postoperative morbidity risk and high survival rates in responders, and could deserve further investigations in randomized clinical trials.
Prognostic factors of overall survival for patients with FIGO stage IIIc or IVa ovarian cancer treated with neo-adjuvant chemotherapy followed by interval debulking surgery: A multicenter cohort analysis from the FRANCOGYN study group
2020, European Journal of Surgical Oncology
The aim of this study was to identify prognostic factors of overall survival in patients with FIGO stage IIIc or IVa ovarian cancer (OC) treated by neo-adjuvant chemotherapy (NAC) followed by interval debulking surgery.
Data from 483 patients with ovarian cancer were retrospectively collected, from January 1, 2000 to December 31, 2016, from the FRANCOGYN database, regrouping data from 11 centers specialized in ovarian cancer treatment. Median overall survival was determined using the Kaplan-Meier method. Univariate and multivariate analysis were performed to define prognostic factors of overall survival.
The median overall survival was 52 after a median follow up of 30 months. After univariate analysis, factors significantly associated with decreased overall survival were; no pelvic and/or para-aortic lymphadenectomy (p = 0.002), residual disease (CC1/CC2/CC3) after surgery (p < 0.001), positive cytology after NAC (p < 0.001), omental disease after NAC (p = 0.002), no pathologic complete response (pCR) (p = 0.002). In multivariate analysis, factors significantly associated with decreased overall survival were; residual disease after surgery (HR = 1.93; CI95% (1.16–3.21), p = 0.01) and positive cytology after NAC (HR = 1.59; CI95% (1.01–2.55), p = 0.05). Patients with no residual disease after surgery had a median overall survival of 64 months versus 35 months for patients with residual disease. Patients with negative cytology after NAC had a median overall survival of 71 months versus 43 months for patients with positive cytology after NAC.
In this first and largest French based retrospective study, complete cytoreductive surgery in ovarian cancer remains the main prognostic factor of overall survival.
Pathologic chemotherapy response score in epithelial ovarian cancer: Surgical, genetic, and survival considerations
2020, Surgical Oncology
A pathologic chemotherapy response score (CRS) is used to grade ovarian cancer response to neoadjuvant chemotherapy (NACT). We evaluated the prognostic significance of the CRS in a single institution cohort.
A retrospective review of all consecutive epithelial ovarian cancer patients undergoing interval debulking surgery (IDS) after NACT from 2016 to 2017 were included. Clinical, pathologic, surgical, outcomes, and genetic data were abstracted from medical records. CRS was assigned by pathology based on a section of omentum as follows: 1 = minimal response, 2 = moderate response, and 3 = near complete response.
Among the 50 subjects, 14 (28%) were classified as CRS1, 29 (58%) as CRS2, and 7 (14%) as CRS3. The majority of patients were diagnosed with high grade serous histology (94%). Most women in this cohort underwent either an optimal or complete cytoreduction to no gross residual disease (96%). Women in the CRS2 group were most likely to have a pathogenic variant (51.7%) while those in the CRS1 were least likely (7.1%). Most women recurred regardless of CRS. CRS was not associated with progression-free survival (log-rank p = 0.82) or overall survival (log-rank p = 0.30).
Though previous data support the use of CRS as a prognostic indicator, we failed to show a correlation between CRS and survival in our continuous single institution cohort. The high rate of optimal debulking across all CRS groups in this study may mitigate the prognostic significance of the scoring system. Nevertheless, tumors that respond poorly to traditional chemotherapy should remain of avid interest for potential novel therapies.
Minimal residual disease at primary debulking surgery versus complete tumor resection at interval debulking surgery in advanced epithelial ovarian cancer: A survival analysis
2020, Gynecologic Oncology
To compare survival outcomes and peri-operative complications in patients with advanced ovarian cancer with 1–10 mm residual disease (RD) at primary debulking surgery (PDS) versus those achieving no gross residual disease (NGR) at interval debulking surgery (IDS).
Patients operated with the intent of complete cytoreduction for epithelial ovarian/fallopian tube/primary peritoneal cancer, FIGO stage IIIC-IV, RD 1–10 mm at PDS and NGR at IDS, between 01/2010 and 12/2016, were retrospectively included. All patients had at least 2-years of follow-up completed.
207 patients were included (59 PDS and 148 IDS). Patients in PDS group were younger and had a higher surgical complexity score. There was a higher rate of intra- and major early post-operative complications in the group of PDS vs IDS (16.9% vs 1.3% and 28.8% vs 2.0%, p < 0.0001 respectively). After a median follow up of 56.4 months (range 59.2–65.4), 117 (56.5%) patients died of disease in the whole population. Forty-eight (81.4%) patients had progression/recurrent disease in the PDS group and 120 (81.1%) in the IDS group. Median PFS was 16.2 months and 18.9 months for PDS and IDS group, respectively (p = 0.111). Median OS was 41.4 months and 52.4 months for PDS and IDS group, respectively (p = 0.022).
IDS should be considered the preferred treatment in case millimetric residual disease is expected at PDS in view of the superimposable PFS and the reduced number of perioperative complications.

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: The authors report no conflict of interest.

: Cite this article as: Petrillo M, Zannoni GF, Tortorella L, et al. Prognostic role and predictors of complete pathologic response to neoadjuvant chemotherapy in primary unresectable ovarian cancer. Am J Obstet Gynecol 2014;211:632.e1-8.

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ResearchGynecologyPrognostic role and predictors of complete pathologic response to neoadjuvant chemotherapy in primary unresectable ovarian cancer

Objective

Study Design

Results

Conclusion

Section snippets

Materials and Methods

Results

Comment

Gynecol Oncol

Gynecol Oncol

Gynecol Oncol

Gynecol Oncol

Gynecol Oncol

Gynecol Oncol

Eur J Cancer

Gynecol Oncol

J Thorac Oncol

Gynecol Oncol

Gynecol Oncol

Research
Gynecology
Prognostic role and predictors of complete pathologic response to neoadjuvant chemotherapy in primary unresectable ovarian cancer