Interval between secondary cytoreductive surgery and adjuvant chemotherapy is not associated with survivals in patients with recurrent ovarian cancer

Abstract Background Secondary cytoreductive surgery (SCS) is possible in selected patients with recurrent epithelial ovarian cancer (EOC). The goal of SCS is complete resection, although chemotherapy is always followed. Delayed intervals between primary debulking surgery and adjuvant chemotherapy was reported to be associated with poorer survivals, however, the role of intervals in recurrent disease is still unknown. Materials and methods This retrospective cohort study reviewed data from electronic medical records of women with recurrent EOC treated at Samsung Medical Centre, Seoul, Korea, between January 1, 2002, and December 31, 2015. Patients who underwent SCS with adjuvant chemotherapy for recurrent EOC were eligible. We defined intervals as the period between the day of SCS and the first cycle of adjuvant chemotherapy. Results Seventy-nine patients were eligible for this study. Their median age was 48 (range, 18–69) years and median interval between the date of SCS and initiation of adjuvant chemotherapy was 10 (range, 4–115) days. The rate of complete resection was 72.2% (57/79). Division of the patients by interval (Group 1, interval ≤ 10 days; Group 2, interval > 10 days) revealed no difference in clinical parameters. No gross residual disease after SCS (no vs. any gross residual, p = 0.002) and longer platinum-free survival (over 12 vs. 6–12 months, p = 0.023) were independent favorable prognostic factors in Cox model; however, the intervals did not affect survival. Conclusions Delayed intervals to adjuvant chemotherapy after secondary cytoreductive surgery is not associated with decreased survivals. It is important to identify recurrent EOC patients who might have no gross residual disease following SCS. Moreover, surgeons should strive for complete resection.

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Randomized controlled phase III study evaluating the impact of secondary cytoreductive surgery in recurrent ovarian cancer: AGO DESKTOP III/ENGOT ov20.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.5501 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 5501-5501 ◽

Cited By ~ 75

Author(s):

Andreas Du Bois ◽

Ignace Vergote ◽

Gwenael Ferron ◽

Alexander Reuss ◽

Werner Meier ◽

...

Keyword(s):

Ovarian Cancer ◽

Cytoreductive Surgery ◽

Recurrent Ovarian Cancer ◽

Complete Resection ◽

Phase Iii ◽

Secondary Cytoreductive Surgery ◽

Initial Surgery ◽

Ago Score ◽

The Impact

5501 Background: The role of secondary cytoreductive surgery in recurrent ovarian cancer (OC) has not been defined by level-1 evidence. Methods: Pts with OC and 1st relapse after 6+ mos platin-free interval (TFIp) were eligible if they presented with a positive AGO-score (PS ECOG 0, ascites ≤500 ml, and complete resection at initial surgery) and were randomized to 2nd-line chemotherapy alone vs cytoreductive surgery followed by chemo. Chemo regimens were selected according to the institutional standard. We report here results of the predetermined interim analysis. Results: 407pts were randomized 2010-2014. The TFIp exceeded 12 mos in 75% and 76% pts in both arms. 8.9% of 203 pts were operated despite of randomization to the no-surgery arm, whereas 6.9% of 204 pts in the surgery arm did not undergo operation. Complete resection was achieved in 67% of pts; 87% and 88% received a platinum-containing 2nd-line therapy. Median PFS was 14 mos without and 19.6 mos with surgery (HR: 0.66, 95%CI 0.52-0.83, p<0.001). Median time to start of first subsequent therapy (TFST) was 21 vs 13.9 mos in favor of the surgery arm (HR 0.61, 95%CI 0.48-0.77, p=p<0.001). PFS-2 between 1st and 2nd relapse equaled or even exceeded PFS-1 before 1strelapse in 26% after surgery and only 16% without-surgery. Analysis of the primary endpoint OS is kept blinded due to immaturity and will be evaluated after extended follow-up (the observed pooled unblinded 2-YSR was 83% instead of the initially in the protocol assumed 55-66%). 60d mortality rates were 0 and 0.5% in the surgery and no-surgery arm. Re-laparatomies were performed in 7 pts (3.5%) in the surgery arm.With the exception of myelosuppression which occurred more frequently in the no-surgery arm no further significant differences were observed with respect to grade 3+ acute adverse events. Conclusions: Surgery in pts with 1st relapse of OC after a TFIp of 6+ mos and selected by a positive AGO-Score resulted in a clinically meaningful increase of PFS and TFST with acceptable treatment burden. Until final OS data will definitively define the role of secondary cytoreductive surgery it should at least be considered as valuable option in pts with a positive AGO-Score. Clinical trial information: NCT01166737.

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The survival outcome and complication of secondary cytoreductive surgery plus chemotherapy in recurrent ovarian cancer: a systematic review and meta-analysis

Journal of Ovarian Research ◽

10.1186/s13048-021-00842-9 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Ting Ding ◽

Dan Tang ◽

Mingrong Xi

Keyword(s):

Ovarian Cancer ◽

Cohort Studies ◽

Cytoreductive Surgery ◽

Survival Benefit ◽

Meta Analysis ◽

Recurrent Ovarian Cancer ◽

Complete Resection ◽

Cochrane Central Register ◽

Incomplete Resection ◽

Secondary Cytoreductive Surgery

Abstract Objective The aim of this meta-analysis was to assess the effectiveness and safety of secondary cytoreductive surgery plus chemotherapy (SCS + CT) in recurrent ovarian cancer (ROC). Our secondary purpose was to analyze whether patients could benefit from complete resection. Methods We searched EMBASE, MEDLINE, the Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials, from inception to April 2021. We used appropriate scales to assess the risk of bias. Data from included studies that reported median PFS or OS were weighted by individual study sample size, and aggregated for meta-analysis. We calculated the pooled proportion of complications within 30 days after surgery. Results We identified 13 articles, including three RCTs and ten retrospective cohort studies. A total of 4572 patients were included, of which 916 patients achieved complete resection, and all patients were comparable at baseline. Compared with chemotherapy alone, SCS + CT significantly improved the PFS (HR = 0.54, 95% CI: 0.43–0.67) and OS (HR = 0.60, 95% CI: 0.44–0.81). Contrary to the results of cohort studies, the meta-analysis of RCTs showed that SCS + CT could not bring OS benefits (HR = 0.93, 95% CI: 0.66–1.3). The subgroup analysis showed the prognostic importance of complete resection. Compared with chemotherapy alone, complete resection was associated with longer PFS (HR = 0.53, 95% CI: 0.45–0.61) and OS (HR = 0.56, 95% CI: 0.39–0.81), while incomplete resection had no survival benefit. Additionally, complete resection could maximize survival benefit compared with incomplete resection (HR = 0.56, 95% CI: 0.46–0.69; HR = 0.61, 95% CI: 0.50–0.75). The pooled proportion for complications at 30 days was 21% (95% CI: 0.12–0.30), and there was no statistical difference in chemotherapy toxicity between the two groups. Conclusion The review indicated that SCS + CT based regimens was correlated with better clinical prognosis for patients with recurrent ovarian cancer, but the interpretation of OS should be cautious. The meta-analysis emphasizes the importance of complete resection, suggesting that the potential benefits of prolonging survival may outweigh the disadvantages of any short-term complications associated with surgery.

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Randomized phase III study to evaluate the impact of secondary cytoreductive surgery in recurrent ovarian cancer: Final analysis of AGO DESKTOP III/ENGOT-ov20.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.6000 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 6000-6000 ◽

Cited By ~ 14

Author(s):

Andreas Du Bois ◽

Jalid Sehouli ◽

Ignace Vergote ◽

Gwenael Ferron ◽

Alexander Reuss ◽

...

Keyword(s):

Ovarian Cancer ◽

Primary Endpoint ◽

Cytoreductive Surgery ◽

Recurrent Ovarian Cancer ◽

Complete Resection ◽

Phase Iii ◽

Incomplete Resection ◽

Second Line ◽

Secondary Cytoreductive Surgery ◽

Ago Score

6000 Background: The role of secondary cytoreductive surgery in recurrent ovarian cancer (ROC) has been under debate for decades. A recent trial in unselected patients (pts) failed to show an OS benefit. Methods: Pts with ROC and 1st relapse after 6+ months (mos) platinum-free interval (TFIp) were eligible if they presented with a positive AGO-score (PS ECOG 0, ascites ≤500 ml, and complete resection at initial surgery) and were prospectively randomized to second-line chemotherapy alone vs. cytoreductive surgery followed by the same chemotherapy; platinum combination therapy was recommended. OS was primary endpoint in this superiority trial. Results: 407pts were randomized 2010-2014. The TFIp exceeded 12 mos in 75% of pts. 206 pts were allocated to the surgery arm of whom finally 187 (91%) were operated. A complete resection was achieved in 75%; almost 90% in both arms received a platinum-containing second-line chemo. Primary endpoint analysis showed median OS of 53.7 mos with and 46.2 mos without surgery (HR 0.76, 95%CI 0.59-0.97, p=0.03); median PFS was 18.4 and 14 mos (HR: 0.66, 95%CI 0.54-0.82, p<0.001), median time to start of first subsequent therapy (TFST) was 17.9 vs. 13.7 mos in favor of the surgery arm (HR 0.65, 95%CI 0.52-0.81, p<0.001). An analysis according to treatment showed an OS benefit exceeding 12 mos for pts with complete resection (CR) compared to pts without surgery (median 60.7 vs. 46.2 mos); pts with surgery and incomplete resection even did worse (median 28.8 mos). 60 d mortality rates were 0 and 0.5% in the surgery and no-surgery arm. Re-laparotomies were performed in 3.7% of operated pts. Further grade 3/4 adverse events did not differ significantly between arms. Conclusions: This is the first surgical study demonstrating a meaningful survival benefit in OC: Surgery in pts with first relapse and TFIp of 6+ mos and selected by a positive AGO-Score resulted in a significant increase of OS, PFS and TFST with acceptable morbidity and, therefore, should be offered to suitable pts. The benefit was exclusively seen in pts with CR indicating the importance of both the optimal selection of pts (eg. by AGO score) and of centres with expertise and a high chance of achieving a CR. Clinical trial information: NCT01166737.

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Platinum and taxane intraperitoneal chemotherapy after secondary cytoreductive surgery for recurrent ovarian carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.16043 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 16043-16043

Author(s):

L. G. Seamon ◽

S. Seward ◽

D. Richardson ◽

J. M. Fowler ◽

D. E. Cohn

Keyword(s):

Ovarian Cancer ◽

Ovarian Carcinoma ◽

Intraperitoneal Chemotherapy ◽

Cytoreductive Surgery ◽

Residual Disease ◽

Recurrent Ovarian Cancer ◽

Platinum Sensitive ◽

Secondary Cytoreductive Surgery ◽

Grade 3 ◽

Platinum Chemotherapy

16043 Background: Intraperitoneal chemotherapy (IP) after primary optimal debulking for advanced stage epithelial ovarian carcinoma improves survival. The objective of this research is to describe our experience with IP taxane and platinum chemotherapy after optimal secondary cytoreductive surgery in patients with platinum-sensitive recurrent ovarian cancer. Methods: We retrospectively reviewed charts from January 2006 to January 2007 and identified approximately 30 patients who received IP chemotherapy for optimally debulked advanced ovarian carcinoma. Of these patients, 8 were treated at first recurrence with cytoreductive surgery followed by second-line IP chemotherapy with intravenous docetaxel (70 mg/m2) and IP cisplatin (75–85 mg/m2) on day 1 and IP paclitaxel (60 mg/m2) on day 8, every 21 days. Results: The median disease free interval from completion of initial chemotherapy to recurrence was 19 months. All patients who underwent secondary cytoreductive surgery were considered optimally debulked (less than 1 cm residual disease), with 6 patients having no residual disease. One patient required rectal resection and another patient had ileocecal resection without a protective ostomy. All patients had insertion of an intraperitoneal venous access device for infusion of IP chemotherapy at the time of cytoreduction. While four patients have completed all 6 cycles of IP chemotherapy, one patient completed only 3 cycles due to catheter related toxicity requiring removal of the port (abdominal pain). This patient did not undergo concurrent bowel surgery. In addition, two patients have completed 3 cycles and two patients are currently scheduled to begin IP chemotherapy. Only two patients experienced grade 3 or 4 neutropenia. No other grade 3 or 4 toxicities were identified. A median of 5 cycles (range 2–5 cycles) was required to achieve a CA125 nadir. Complete clinical response was obtained in all patients at a median follow up of 9 months (range 4–10 months). Conclusions: In optimally debulked, platinum-sensitive patients following secondary cytoreductive surgery for recurrent ovarian cancer, intraperitoneal taxane and platinum chemotherapy is feasible with acceptable toxicity and provides another option for treatment. No significant financial relationships to disclose.

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Randomized controlled phase III study to evaluate the impact of secondary cytoreductive surgery in recurrent ovarian cancer – AGO DESKTOP III/ENGOT ov20

10.1055/s-0038-1671029 ◽

2018 ◽

Author(s):

P Harter ◽

J Sehouli ◽

W Meier ◽

A Reuss ◽

P Hillemanns ◽

...

Keyword(s):

Ovarian Cancer ◽

Cytoreductive Surgery ◽

Recurrent Ovarian Cancer ◽

Phase Iii ◽

Randomized Controlled ◽

Secondary Cytoreductive Surgery ◽

Phase Iii Study ◽

The Impact

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Ovarialkarzinomrezidiv: Sollte operiert werden oder reicht die medikamentöse Therapie?

Karger Kompass Onkologie ◽

10.1159/000513159 ◽

2020 ◽

Vol 7 (4) ◽

pp. 199-200

Author(s):

Martin Pölcher

Keyword(s):

Primary Endpoint ◽

Cytoreductive Surgery ◽

Recurrent Ovarian Cancer ◽

Complete Resection ◽

Incomplete Resection ◽

Second Line ◽

Recent Trial ◽

Secondary Cytoreductive Surgery ◽

Initial Surgery ◽

Ago Score

Background: The role of secondary cytoreductive surgery in recurrent ovarian cancer (ROC) has been under debate for decades. A recent trial in unselected patients (pts) failed to show an OS benefit. Methods: Pts with ROC and 1st relapse after 6+ months (mos) platinum-free interval (TFIp) were eligible if they presented with a positive AGO-score (PS ECOG 0, ascites ≤500 ml, and complete resection at initial surgery) and were prospectively randomized to second-line chemotherapy alone vs. cytoreductive surgery followed by the same chemotherapy; platinum combination therapy was recommended. OS was primary endpoint in this superiority trial. Results: 407pts were randomized 2010–2014. The TFIp exceeded 12 mos in 75% of pts. 206 pts were allocated to the surgery arm of whom finally 187 (91%) were operated. A complete resection was achieved in 75%; almost 90% in both arms received a platinum-containing second-line chemo. Primary endpoint analysis showed median OS of 53.7 mos with and 46.2 mos without surgery (HR 0.76, 95%CI 0.59–0.97, p = 0.03); median PFS was 18.4 and 14 mos (HR: 0.66, 95%CI 0.54–0.82, p < 0.001), median time to start of first subsequent therapy (TFST) was 17.9 vs. 13.7 mos in favor of the surgery arm (HR 0.65, 95%CI 0.52–0.81, p < 0.001). An analysis according to treatment showed an OS benefit exceeding 12 mos for pts with complete resection (CR) compared to pts without surgery (median 60.7 vs. 46.2 mos); pts with surgery and incomplete resection even did worse (median 28.8 mos). 60 d mortality rates were 0 and 0.5% in the surgery and no-surgery arm. Re-laparotomies were performed in 3.7% of operated pts. Further grade 3/4 adverse events did not differ significantly between arms. Conclusions: This is the first surgical study demonstrating a meaningful survival benefit in OC: Surgery in pts with first relapse and TFIp of 6+ mos and selected by a positive AGO-Score resulted in a significant increase of OS, PFS and TFST with acceptable morbidity and, therefore, should be offered to suitable pts. The benefit was exclusively seen in pts with CR indicating the importance of both the optimal selection of pts (eg. by AGO score) and of centres with expertise and a high chance of achieving a CR. Clinical trial information: NCT01166737.

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