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Abstract

Cytoreductive surgery is accepted as a major treatment of primary ovarian cancer. The role in recurrent ovarian cancer remains a field of discussion and controversy, mainly owing to missing data from prospective randomized trials and lack of universal definitions. Retrospective data indicate that complete resection of recurrent tumor formations should be aimed for, since survival prolongation is mainly seen for patients with no residual disease. Thus, it is most important to find predictors of complete resection, on the one hand to offer the best therapeutic chances to patients, but on the other hand to protect patients with limited life expectancy from additional surgical burden. The first prospective surgical trial in recurrent ovarian cancer, AGO-DESKTOP II validated a score (‘AGO score’) for complete resection. It was shown that patients with a good general condition (ECOG 0), no residual disease after surgery for primary ovarian cancer and absence of ascites in presurgical diagnostics have a 76% likelihood of undergoing complete resection. In this article, further recent data regarding surgery for recurrent ovarian cancer are going to be discussed and the advantages of incorporating these patients into randomized trials are highlighted.

Keywords

AGO-DESKTOP ovarian cancer platinum-sensitive ovarian cancer recurrent ovarian cancer secondary cytoreductive surgery surgery

Epithelial ovarian carcinoma is the second most common genital malignancy in females and accounts for the majority of deaths from gynecologic malignancies. To date, no screening methods to detect ovarian cancer at an early stage have been developed, thus approximately 60–70% of women with newly diagnosed ovarian cancer present with advanced disease [1,2]. Nevertheless, complete clinical remission can be achieved in approximately 80% of these patients with the use of maximal surgical cytoreduction and platinum-based combination chemotherapy [1]. Today a combination of carboplatin and paclitaxel is the standard primary chemotherapy regime [3,4]. Unfortunately, upwards of 75% of patients with clinical complete response will develop recurrent disease. Recent studies have reported encouraging results in women with platinum-sensitive relapsed ovarian cancer (platinum-free interval >6 months) treated with pegylated liposomal doxorubicin [5], paclitaxel [6] or gemcitabine [7] in combination with carboplatin. For patients with platinum-resistant relapsed ovarian cancer, many drugs are available but pegylated liposomal doxorubicin [8], topotecan [9,10] or gemcitabine [11,12] are the most commonly used as monotherapy.

General considerations regarding surgery in recurrent ovarian cancer

While cytoreductive surgery in primary epithelial ovarian cancer is considered the standard of care [13], there are still many open questions in surgery for recurrent ovarian cancer and the benefit remains a matter of controversy. Currently there in no level I evidence for surgery in recurrent ovarian cancer. Furthermore, the definition of secondary cytoreductive surgery is not consistently used, and different studies included different groups of patients, namely patients with recurrent disease and those with persistent disease. Moreover, even patients with either progressive disease at the end of chemotherapy or patients with persisting, but not progressing, ovarian cancer, as well as both patients with small residual tumors that responded to systemic treatment and patients suffering from recurrence after a disease-free period of some weeks or several years, have been included [14,15]. For these subgroups, survival times of up to 9 months were reported, not justifying cytoreductive surgery with a morbidity rate of up to 24% in this setting. Therefore, it is necessary to have clear definitions of different types of surgery in ovarian cancer (Box 1).

This article focuses on cytoreductive surgery for recurrent ovarian cancer, which is defined as an operation performed in patients with recurrent disease after completion of primary treatment (surgery with or without chemotherapy) and a period without any evidence of disease.

What should be the aim of surgery for recurrent ovarian cancer?

The phrase of ‘optimal debulking’ has been introduced for primary cytoreductive surgery in advanced ovarian cancer. Retrospective studies reported a threshold above which cytoreduction did not result in a more favorable outcome and defined all lesions with a maximum diameter of ≤1 cm of the residual tumor as cut-off for inclusion criteria [16,17] or as stratum [3,18,19]. Nowadays this paradigm has changed towards complete resection of all visible tumor manifestations, owing to recently published reports [20 –22], and the Gynecologic Cancer Interstudy Group (GCIG) has changed the official nomenclature to that effect [4]. However, the concept of “optimal debulking” has not been established in cytoreductive surgery for recurrent disease.

Box 1.

Surgical procedures in recurrent ovarian cancer.

Surgical procedures in ovarian cancer

This type of surgery could be performed at any time in the course of ovarian cancer (e.g., to get a histological diagnosis). Second-look surgery belongs to this group of procedures. It is an operation performed in patients who are clinically, biochemically and radiologically free of disease after the completion of a defined course of chemotherapy with the purpose to confirm the response status (in principle, the removal of the remaining tumor at second-look passes the border of diagnostic procedures)

Staging laparotomy

This surgery should be performed in patients with macroscopically early ovarian cancer limited to the ovaries or the pelvis. The aim of this surgery is the detection of tumor spread

Primary cytoreductive surgery

Surgery with the aim of complete resection of all macroscopic tumors in patients with first diagnosis of ovarian cancer before any other treatment modalities (e.g., chemotherapy)

Secondary surgery/interval debulking

An operation performed in patients after chemotherapy, usually two or three cycles, with an attempt to remove any remaining tumor that has not been removed by chemotherapy, followed by additional cycles of chemotherapy

Surgery for progressive ovarian cancer

An operation with the purpose of removing obviously resistant tumors that have not responded to chemotherapy and progressed during primary chemotherapy

Surgery for recurrent ovarian cancer

Surgery aiming for complete resection of all macroscopic tumor in patients with recurrent ovarian cancer after completion of primary therapy including a subsequent period without any signs of disease

Palliative surgery

An operation performed in patients with symptoms caused by progressive disease or sequelae from prior treatment. These operations are performed in an effort to relieve symptoms and do not aim primarily at survival prolongation

Adapted from Harter et al. [41].

The definition of optimal debulking is varying and ranges between “removal of all visible tumor” and “small residuals” with different dimensions of maximum diameters (0.5–2.0 cm).

Complete debulking rates varied between 9 and 82% in a systematic review comprising retrospective studies with more than 20 patients [23] and between 9 and 100% in a meta-analysis using all published data between 1983 and 2007 [24]. All but one series were collected retrospectively and were obviously exposed to selection bias. Unfortunately, information regarding selection criteria and proportions of patients who were not intended for cytoreductive surgery was lacking in most reports. If reported, the rate of patients not being offered surgery varied between 7 and 64%.

Even larger series (>100 included patients) dealing with cytoreductive surgery for recurrent disease provided controversial findings concerning the impact of the scale of surgical intervention. Eisenkop et al. [25], Harter and du Bois [23] and Sehouli et al. [26] reported a significant survival benefit only for patients with complete resection, whilst Scarabelli et al. [27] and Zang et al. [28] also indicated a benefit for so-called optimally debulked patients with residual disease of less than 1 cm. The sixth series defined residuals up to 0.5 cm as ‘optimal’ and found a significant prognostic benefit in patients with residuals less than 0.5 cm [29]. Of note, in this series only a minority of patients had residual disease between 0.1 and 0.5 cm. The Kaplan–Meier curve showed poorer prognosis for this subgroup of patients compared with completely debulked patients and p-values that always depend on numbers of events, showed no statistical difference. Interestingly, the latter three series reported lower complete resection rates (11, 41 and 42%) than Harter and Eisenkop (50 and 81%, respectively), thus raising questions about different selection criteria, different surgical approaches, and methodological proceedings. A recent meta-analysis out of most studies for surgery in recurrent ovarian cancer found that obtaining complete resection in an additional 10% of patients increases median survival by 3 months [24], which was even detectable in the multivariate model.

In conclusion, the aim of surgery in recurrent ovarian cancer should be complete resection, as the described benefit of so-called ‘optimal debulking’ in some series is very low and probably a false finding. Therefore, if complete resection is not feasible, the aim of surgery should change from cytoreduction to palliation with the aim to minimize surgical comorbidity and to start chemotherapy as soon as possible.

Is it possible to predict complete resection in recurrent ovarian cancer?

The presence of symptoms, localization of disease, number of disease sites and treatment-free interval were reported as predictive factors for complete resection in univariate analyses. Cancer-Antigen (CA)-125 elevation was also found to be predictive in univariate analyses, and most recently it has been shown that the rate of complete resection declines by approximately by 3% per week after first CA-125 elevation was noticed and no surgery was performed [30].

Four retrospective series reported multivariate analyses of predictive factors associated with favorable surgical outcome. Absence of preoperative salvage chemotherapy, good performance status and a size of recurrent disease of less than 10 cm were predictors for complete debulking [25]. In another series with 38 patients, the number of disease sites (solitary vs multiple) was an independent factor for complete resection [31] and absence of ascites and residual disease after primary surgery were reported as predictors for complete resection [32]. The Descriptive Evaluation of preoperative Selection KriTeria for OPerability in recurrent OVARian cancer (DESKTOP OVAR) I trial conducted by the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) identified a combination of predictive parameters for complete resection: good performance status (Eastern Cooperative Oncology Group 0), no residual disease after surgery for primary ovarian cancer (alternatively, if unknown, early initial Fédération Internationale de Gynécologie et d'Obstétrique [FIGO] stage) and absence of ascites in presurgical diagnostics. Complete resection was achieved in 79% of patients scoring all these factors. If not all factors were positive, a complete resection was achieved in only 43% [33]. The latter group could be further differentiated: complete resection was achieved in 74% of this subgroup if there was no peritoneal carcinomatosis found intraoperatively, otherwise only 26% could be completely debulked [34].

In the subsequent AGO-DESKTOP II trial the ‘AGO score’ was validated in a prospective multicenter study. A total of 512 patients with platinum-sensitive relapse were screened and 261 patients (51%) presented with good performance status, complete resection at primary surgery and absence of ascites, and were defined as ‘AGO score’ positive. From these, 129 patients (49.4%) had their first relapse and underwent surgery for recurrent disease. A positive ‘AGO score’ resulted in a complete resection rate of 76%, thus the score was successfully validated [35]. In conclusion, the ‘AGO score’ (Box 2) may help to identify patients in whom complete resection of relapsed ovarian cancer is most likely.

Does complete resection translate into survival benefit in recurrent ovarian cancer?

The median survival of completely debulked patients ranges from 16 to 100 months [23] and overlaps with the median survival described in recently reported large prospective trials in recurrent platinum-sensitive ovarian cancer (i.e., ICON4/AGO-OVAR 2.2 [6] and the GCIG study AGO-OVAR 2.5 [7]). These studies reported a median survival of 18 and 29 months in the respective superior arms. The majority of series on cytoreductive surgery for recurrent ovarian cancer did not report median survival exceeding the ICON4/AGO-OVAR 2.2 results.

In conclusion, the lack of randomized trials makes it impossible to conclude whether a more favorable outcome in series with high rates of complete debulking could be attributed to biology (i.e., selection bias) or to surgical results.

Which prognostic factors are associated with prolonged survival in patients who received cytoreductive surgery for recurrent ovarian cancer?

Almost all series reported a relationship between survival and surgical outcome in univariate analysis. Complete debulking was one of the strongest predictors for survival in all multivariate analyses performed. All other analyzed factors provided controversial results. Treatment-free interval before cytoreductive surgery showed no significant impact on outcome in univariate analyses in approximately half of the series, but others reported a significant role. However, only few patients with rather short treatment-free survival were included in the respective series and the proportion of patients with less than 6 months treatment-free survival ranged from 0 to 13.5%. Therefore, the data regarding a possible impact of treatment-free interval periods are mainly valid for different periods beyond 6 months [23]. Eisenkop et al. reported a benefit for treatment-free intervals exceeding 36 months compared with shorter intervals (13–36 and 6–12 months) [25]. The same applies to the series of Chi et al. (>30 months vs 12–30 months vs 6–12 months, respectively) [29]. Scarabelli et al. showed a benefit for the subgroup with a recurrence-free interval of 13–24 months but not for patients with longer (>24 months) or shorter intervals (7–12 months) [27]. The AGO-DESKTOP I trial showed a benefit for a treatment-free interval exceeding 6 months but no difference if intervals longer than 6 months were compared in the univariate analysis (6–12 vs 12–24 vs longer than 24 months, respectively). However, treatment-free interval did not remain an independent factor in the multivariate analysis [34]. A similar observation was reported by Zang et al. who reported a benefit for longer progression-free intervals in a univariate analysis that could not be confirmed by multivariate analysis [28]. The influence of preoperative tumor load on surgical and prognostic outcome is still controversial. Table 1 summarizes all studies with more than 100 included patients with respect to the best-reported tumor residuals, median survival and further prognostic factors. An exploratory analysis of the AGO-DESKTOP I trial has shown that the presence of peritoneal carcinomatosis is a significant negative predictor for complete resection [34].

Table 1.

Summary of series with >100 patients for surgery of recurrent ovarian cancer, reporting smallest achieved residual tumor.

Study (year)	n	Residual tumor (cm)	Median survival (months)	Further factors associated with better prognosis	Ref.
Harter et al. (2006)	267	0	45.2	<500 ml ascites, postoperative platinum containing chemotherapy, ECOG 0	[33]
Chi et al. (2006)	157	<0.5	56	Single site of recurrence, longer disease-free interval	[29]
Scarabelli et al. (2001)	149	0	†	Only one chemotherapy treatment before surgery	[27]
Zang et al. (2000)	117	<1	20	No ascites, longer disease-free interval	[32]
Eisenkop et al. (2000)	106	0	44.4	Longer disease-free interval, no salvage chemotherapy before surgery, largest size of recurrent tumor <10 cm	[25]
Oksefjell et al. (2009)	217	0	54.0	Longer disease-free interval, younger age	[42]
Tian et al. (2010)	123	0	63.2 (mean)	Longer disease-free interval, largest size of recurrent tumor <10 cm; single site of recurrence	[43]
Sehouli et al. (2010)	240	0	42.3	<500 ml ascites, <FIGO IV	[26]

†

2-year survival rates for patients with no macroscopic disease, 56% of patients had a disease-free interval of 7–12 months and 91% had a disease-free interval of 13–24 months.

ECOG: Eastern Cooperative Oncology Group; FIGO: Fédération Internationale de Gynécologie et d'Obstétrique.

Box 2.

‘AGO score’ for patients with epithelial ovarian cancer recurrence.

Good performance status (ECOG0)

No residual disease after surgery for primary treatment (alternatively, if unknown: early initial FIGO stage)

Absence of ascites in presurgical diagnostics

If all three items are existent, a complete resection of recurrent disease is feasible in 76% of all patients.

In addition, platinum-based chemotherapy should be administered after recovery from surgery to eradicate minimal residual disease. The value of hyperthermic intraperitoneal chemotherapy was looked at in a small retrospective analysis, but results were not convincing [36], thus the intravenous route should be the route of chemotherapy application.

Morbidity & mortality in surgery of recurrent ovarian cancer

Depending on the experiences and surgical capabilities, postoperative morbidity and mortality rates are varying, but complication rates in surgery for recurrent ovarian cancer are not significantly higher, compared with primary debulking surgery.

Mean 30-day morbidity after primary cytoreductive surgery for advanced stage ovarian cancer ranges between 22% [37] and 34% [38], while the morbidity rate in a meta-analyses of surgery in recurrent ovarian cancer ranged between 0 and 88.8%, with a weighted mean of 19.2% [24]. In the AGO-DESKTOP II trial, 33% of patients had at least one complication in the postoperative period [35]. Mean 30-day postoperative mortality in primary debulking surgery ranges between 0.7% [39] and 2.8% [40], while the mortality rate of surgery in recurrent ovarian cancer ranges between 0 and 5.5%, with a weighted mean of 1.2% [24], 7.8% in single centers [26] and 0.8% in the AGO-DESKTOP II trial [35]. Nevertheless, these data are very prone to be affected by selection and publication bias, since there is a strict definition neither for morbidity, nor for the observed time after surgery.

Future perspective

Currently, there is no level I evidence for cytoreductive surgery in recurrent ovarian cancer. However, even the most active chemotherapy regimens provided only limited activity with a median survival of 29 months (ICON4/AGO-OVAR 2.2) and improvement is clearly needed for these patients. The series of surgery for recurrent disease reported survival rates of up to 100 months in patients with complete resection, thus far exceeding the median survival rates reported after chemotherapy alone. These findings result from highly selected patient cohorts and, therefore, the main question might be “How can we select suitable patients for cytoreductive surgery in recurrent ovarian cancer?” The available information is far from being conclusive, but some factors were repeatedly cited as predictors for successful surgery. The AGO-DESKTOP II trial was the only one that successfully prospectively validated a score (good performance status, complete resection at primary surgery, absence of ascites) for complete resection in a multicenter setting.

Most recently, the AGO-DESKTOP III trial, “A prospective randomized trial comparing surgery and chemotherapy versus chemotherapy alone in recurrent ovarian cancer”, was launched (NCT01166737) [101]. Another ongoing study investigating the role of cytoreductive surgery for platinum-sensitive recurrent ovarian cancer is being performed by the Gynecologic Oncology Group (GOG) (NCT00565851) [102]. Until conclusive results that define the role of surgery in recurrent ovarian cancer are available, it is feasible to counsel patients regarding their surgical options in recurrent ovarian cancer outside of clinical trials based on the ‘AGO score’ (Table 1).

Executive summary

Approximately 75% of patients with clinical complete response after first-line therapy will develop recurrent disease.

Different definitions have been used to describe surgery for recurrent ovarian cancer. A reasonable definition reads as follows: “surgery aiming for complete resection of all macroscopic tumor in patients with recurrent ovarian cancer after completion of primary therapy including a subsequent period without any signs of disease.”

The aim of surgery in recurrent ovarian cancer should be complete resection.

‘Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) score’: good performance status (Eastern Cooperative Oncology Group [ECOG] 0), no residual disease after surgery for primary ovarian cancer and absence of ascites in presurgical diagnostics.

Prospective AGO-DESKTOP II trial: if the ‘AGO score’ is positive, complete resection is feasible in 76% of patients with recurrent ovarian cancer.

Morbidity and mortality rates in recurrent ovarian cancer do not exceed rates of primary surgery, if conducted in experienced centers.

Footnotes

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

References

Papers of special note have been highlighted as:

of interest

of considerable interest

Heintz

Odicino

Maisonneuve

. Carcinoma of the ovary. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int. J. Gynaecol. Obstet. 95(Suppl. 1), S161–S192 (2006).

Jemal

Siegel

Ward

. Cancer statistics. CA Cancer J. Clin. 60(5), 277–300 (2010).

du Bois

Luck

Meier

. A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J. Nat. Cancer. Int. 95(17), 1320–1329 (2003).

One of two studies defining the current standard of first-line chemotherapy for the treatment of ovarian cancer

Stuart

Kitchener

Bacon

. Gynecologic Cancer InterGroup (GCIG) consensus statement on clinical trials in ovarian cancer: report from the Fourth Ovarian Cancer Consensus Conference. Int. J. Gynecol. Cancer 21(4), 750–755 (2010).

Pujade-Lauraine

Wagner

Aavall-Lundqvist

. Pegylated liposomal Doxorubicin and Carboplatin compared with Paclitaxel and Carboplatin for patients with platinum-sensitive ovarian cancer in late relapse. J. Clin. Oncol. 28(20), 3323–3329 (2010).

10.

A new and effective drug regimen in the armamentarium for treating platinum-sensitive ovarian cancer

11.

Parmar

Ledermann

Colombo

. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet, 361(9375), 2099–2106 (2003).

12.

Pfisterer

Plante

Vergote

. Gemcitabine plus carboplatin compared with carboplatin in patients with platinum-sensitive recurrent ovarian cancer: an intergroup trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG. J. Clin. Oncol. 24(29), 4699–4707 (2006).

13.

Defining one of the most frequent regimens treating platinum-sensitive recurrent ovarian cancer

14.

Gordon

Fleagle

Guthrie

Parkin

Gore

Lacave

. Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J. Clin. Oncol. 19(14), 3312–3322 (2001).

15.

Meier

du Bois

Reuss

. Topotecan versus treosulfan, an alkylating agent, in patients with epithelial ovarian cancer and relapse within 12 months following 1st-line platinum/paclitaxel chemotherapy. A prospectively randomized phase III trial by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group (AGO-OVAR). Gynecol. Oncol. 114(2), 199–205 (2009).

16.

Sehouli

Stengel

Harter

. Topotecan Weekly Versus Conventional 5-Day Schedule in Patients With Platinum-Resistant Ovarian Cancer: a randomized multicenter phase II trial of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group. J. Clin. Oncol. 29(2), 242–248 (2011).

17.

Ferrandina

Ludovisi

Lorusso

. Phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in progressive or recurrent ovarian cancer. J. Clin. Oncol. 26(6), 890–896 (2008).

18.

Mutch

Orlando

Goss

. Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. J. Clin. Oncol. 25(19), 2811–2818 (2007).

19.

du Bois

Quinn

Thigpen

. 2004 consensus statements on the management of ovarian cancer: final document of the 3rd International Gynecologic Cancer Intergroup Ovarian Cancer Consensus Conference (GCIG OCCC 2004). Ann. Oncol. 16(Suppl. 8), viii7–viii12 (2005).

20.

Sharp

Blackett

Leake

Berek

. Conclusions and recommendations from the Helene Harris Memorial Trust Fifth Biennial International Forum on Ovarian Cancer, May 4–7, 1995, Glasgow, UK. Int. J. Gynecol. Cancer 5(6), 449–458 (1995).

21.

Berek

Trope

Vergote

. Surgery during chemotherapy and at relapse of ovarian cancer. Ann. Oncol. 10(Suppl. 1), 3–7 (1999).

22.

McGuire

Hoskins

Brady

. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N. Engl. J. Med. 334(1), 1–6 (1996).

23.

Ozols

Bundy

Greer

. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J. Clin. Oncol. 21(17), 3194–3200 (2003).

24.

The other study defining the current standard of first-line chemotherapy for the treatment of ovarian cancer

25.

Piccart

Bertelsen

James

. Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results. J. Nat. Cancer Int. 92(9), 699–708 (2000).

26.

du Bois

Herrstedt

Hardy-Bessard

. Phase III trial of carboplatin plus paclitaxel with or without gemcitabine in first-line treatment of epithelial ovarian cancer. J. Clin. Oncol. 28(27), 4162–4169 (2010).

27.

Winter

3rd Maxwell

Tian

. Prognostic factors for stage III epithelial ovarian cancer: a Gynecologic Oncology Group Study. J. Clin. Oncol. 25(24), 3621–3627 (2007).

28.

du Bois

Reuss

Pujade-Lauraine

Harter

Ray-Coquard

Pfisterer

. Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized Phase 3 multicenter trials: by the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d'Investigateurs Nationaux Pour les Etudes des Cancers de l'Ovaire (GINECO). Cancer 115(6), 1234–1244 (2009).

29.

The largest trial suggesting that complete debulking in primary surgery of advanced ovarian cancer is of prognostic relevance. One of the studies leading to the new definition of ‘optimal debulking’ as complete resection of all visible tumor

30.

Winter

3rd Maxwell

Tian

. Tumor residual after surgical cytoreduction in prediction of clinical outcome in stage IV epithelial ovarian cancer: a Gynecologic Oncology Group Study. J. Clin. Oncol. 26(1), 83–89 (2008).

31.

Harter

du Bois

. The role of surgery in ovarian cancer with special emphasis on cytoreductive surgery for recurrence. Curr. Opin. Oncol. 17(5), 505–514 (2005).

32.

Bristow

Puri

Chi

. Cytoreductive surgery for recurrent ovarian cancer: a metaanalysis. Gynecol. Oncol. 112(1), 265–274 (2009).

33.

Eisenkop

Friedman

Spirtos

. The role of secondary cytoreductive surgery in the treatment of patients with recurrent epithelial ovarian carcinoma. Cancer 88(1), 144–153 (2000).

34.

Sehouli

Richter

Braicu

. Role of secondary cytoreductive surgery in ovarian cancer relapse: who will benefit? A systematic analysis of 240 consecutive patients. J. Surg. Oncol. 102(6), 656–662 (2010).

35.

Scarabelli

Gallo

Carbone

. Secondary cytoreductive surgery for patients with recurrent epithelial ovarian carcinoma. Gynecol. Oncol. 83(3), 504–512 (2001).

36.

Zang

Zhang

. Effect of cytoreductive surgery on survival of patients with recurrent epithelial ovarian cancer. J. Surg. Oncol. 75(1), 24–30 (2000).

37.

Chi

McCaughty

Diaz

. Guidelines and selection criteria for secondary cytoreductive surgery in patients with recurrent, platinum-sensitive epithelial ovarian carcinoma. Cancer 106(9), 1933–1939 (2006).

38.

Fleming

Cass

Walsh

Karlan

. CA125 surveillance increases optimal resectability at secondary cytoreductive surgery for recurrent epithelial ovarian cancer. Gynecol. Oncol. 121(2), 249–252 (2011).

39.

Gronlund

Lundvall

Christensen

Knudsen

Hogdall

. Surgical cytoreduction in recurrent ovarian carcinoma in patients with complete response to paclitaxel-platinum. Eur. J. Surg. Oncol. 31(1), 67–73 (2005).

40.

Zang

Zhang

. Impact of secondary cytoreductive surgery on survival of patients with advanced epithelial ovarian cancer. Eur. J. Surg. Oncol. 26(8), 798–804 (2000).

41.

Harter

du Bois

Hahmann

. Surgery in recurrent ovarian cancer: the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) DESKTOP OVAR trial. Ann. Surg. Oncol. 13(12), 1702–1710 (2006).

42.

Largest retrospective multicenter study developing a score to predict complete resection in recurrent ovarian cancer

43.

Harter

Hahmann

Lueck

. Surgery for recurrent ovarian cancer: role of peritoneal carcinomatosis: exploratory analysis of the DESKTOP I trial about risk factors, surgical implications, and prognostic value of peritoneal carcinomatosis. Ann. Surg. Oncol. 16(5), 1324–1330 (2009).

44.

Describes the important role of peritoneal carcinomatosis in surgery of recurrent ovarian cancer

45.

Harter

Sehouli

Reuss

. 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. Int. J. Gynecol. Cancer 21(2), 289–295 (2011).

46.

First prospective trial in recurrent ovarian cancer to evaluate the AGO score, predicting complete resection in two out of three patients with a positive score

47.

Helm

Randall-Whitis

Martin

3rd . Hyperthermic intraperitoneal chemotherapy in conjunction with surgery for the treatment of recurrent ovarian carcinoma. Gynecol. Oncol. 105(1), 90–96 (2007).

48.

Chi

Zivanovic

Levinson

. The incidence of major complications after the performance of extensive upper abdominal surgical procedures during primary cytoreduction of advanced ovarian, tubal, and peritoneal carcinomas. Gynecol. Oncol. 119(1), 38–42 (2010).

49.

Gerestein

Nieuwenhuyzen-de Boer

Eijkemans

Kooi

Burger

. Prediction of 30-day morbidity after primary cytoreductive surgery for advanced stage ovarian cancer. Eur. J. Cancer 46(1), 102–109 (2010).

50.

Chi

Franklin

Levine

. Improved optimal cytoreduction rates for stages IIIC and IV epithelial ovarian, fallopian tube, and primary peritoneal cancer: a change in surgical approach. Gynecol. Oncol. 94(3), 650–654 (2004).

51.

Gerestein

Damhuis

Burger

Kooi

. Postoperative mortality after primary cytoreductive surgery for advanced stage epithelial ovarian cancer: a systematic review. Gynecol. Oncol. 114(3), 523–527 (2009).

52.

Harter

Hilpert

Mahner

Kommoss

Heitz

du Bois

. Role of cytoreductive surgery in recurrent ovarian cancer. Expert Rev. Anticancer Ther. 9(7), 917–922 (2009).

53.

Oksefjell

Sandstad

Trope

. The role of secondary cytoreduction in the management of the first relapse in epithelial ovarian cancer. Ann. Oncol. 20(2), 286–293 (2009).

54.

Tian

Jiang

Cheng

Tang

Xing

Zang

. Surgery in recurrent epithelial ovarian cancer: benefits on survival for patients with residual disease of 0.1–1 cm after secondary cytoreduction. J. Surg. Oncol. 101(3), 244–250 (2010).

55.

Study Comparing Tumor Debulking Surgery Versus Chemotherapy Alone in Recurrent Platinum-Sensitive Ovarian Cancer http://clinicaltrials.gov/ct2/results?term=NCT01166737

56.

Carboplatin and Paclitaxel With or Without Bevacizumab After Surgery in Treating Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer http://clinicaltrials.gov/ct2/results?term=NCT00565851

Surgery for Recurrent Ovarian Cancer

Abstract

Keywords

General considerations regarding surgery in recurrent ovarian cancer

What should be the aim of surgery for recurrent ovarian cancer?

Is it possible to predict complete resection in recurrent ovarian cancer?

Does complete resection translate into survival benefit in recurrent ovarian cancer?

Which prognostic factors are associated with prolonged survival in patients who received cytoreductive surgery for recurrent ovarian cancer?

Morbidity & mortality in surgery of recurrent ovarian cancer

Future perspective

Footnotes

References