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Beyond the beyond: first case of 9 cytoreductive surgeries in a long-surviving ovarian cancer patient: case report

Abstract

Background

The role of surgery in recurrent ovarian cancer (ROC) is debated. Multiple prospective and retrospective series reported improved survival with optimal secondary surgical cytoreduction, but definitive results from randomized trials are needed. Up to the fourth cytoreductive surgery for recurrent disease in an attempt to improve patients’ prognosis has been reported.

Case report

We report the first case of multiple ROC in an Italian woman, 50 years old at diagnosis, who underwent 9 cytoreductive surgeries during her 17 years of disease with no serious postoperative complications.

Conclusions

Multiple surgeries should not be considered as the standard treatment for ROC. In carefully selected patients, optimal cytoreductive surgery performed by highly specialized gynecologic oncologists might represent a useful tool in adjunction to chemotherapy for the management of ROC.

Tumori 2016; 102(Suppl. 2): e78 - e81

Article Type: CASE REPORT

DOI:10.5301/tj.5000427

Authors

Laura Salerno, Claudia Marchetti, Elisa Bevilacqua, Angela Musella, Lucia Riganelli, Ilary Ruscito, Giorgia Perniola, Ludovico Muzii, Pierluigi Benedetti Panici

Article History

Disclosures

Financial support: None.
Conflict of interest: None.

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Introduction

After the completion of first-line treatment for ovarian cancer, 60% of cases are destined to recur (1). In the setting of optimally debulked platinum-sensible recurrent disease, secondary cytoreductive surgery is emerging as the preferable choice in absence of peritoneal carcinomatosis with respect to chemotherapy alone, since it appears to improve progression-free survival and overall survival (2, 3). In particular, the achievement of no residual tumor at recurrent surgery has been observed to be the most important prognostic factor, radically influencing the course of events (4, 5). The advantage of repeated optimal cytoreductive surgeries for recurrent patients is counterbalanced by an increasing perioperative morbidity rate (6).

We report the case of a patient with stage IIIC platinum-resistant ovarian cancer subjected to 9 successive cytoreductive surgeries for recurrent disease who survived for 17 years with no severe complications.

Case report

We report the case of an Italian woman, admitted to our institution in May 1997, at age 50 years, who was diagnosed with adnexal complex masses, no ascites, and negative values of carbohydrate antigen (CA) 125. No family history of gynecologic malignancies was referred. She underwent primary cytoreductive surgery and an optimal debulking (residual tumor [RT] = 0) was achieved. Histology revealed a serous papillary poorly differentiated ovarian carcinoma. The patient was staged IIIC ovarian cancer according to International Federation of Gynaecology and Obstetrics (FIGO) classification and was submitted to 6 cycles of epirubicin-cisplatin-paclitaxel-based adjuvant chemotherapy. A computed tomography (CT) scan performed 1 month after last chemotherapy revealed no evidence of disease. Three months after the completion of first-line treatment, CT scan revealed disease recurrence involving right inguinal lymph nodes with no increase of serum CA125. The surgeon proposed a second surgical debulking and the patient was submitted to right inguinal lymphadenectomy and diagnostic laparoscopy followed by 6 cycles of topotecan-based chemotherapy. No residual tumor was obtained. She remained disease-free for 17 months, after which she recurred again. Ovarian cancer metastases occurred as nodules involving the right diaphragm, the third hepatic segment, and the rectosigmoidal serosa. In accordance with the patient’s will, who was strongly motivated to have another surgical removal of the disease rather than medical treatment alone, the surgeon carried out an optimal third cytoreduction followed by 6 cycles of weekly paclitaxel. No perioperative morbidity was reported. Follow-up was negative for 32 months, after which she experienced widespread disease recurrence. Metastases appeared to be localized at para-aortic lymph nodes, spleen, and periumbilical skin. After careful counseling regarding the risks of a new extensive surgery, the surgeon and patient decided to attempt a fourth cytoreduction consisting of splenectomy, para-aortic lymphadenectomy, and periumbilical skin metastasis dissection. The surgical intervention was successfully performed, with no residual tumor or perioperative morbidity reported. The patient underwent 6 cycles of carboplatin plus paclitaxel-based chemotherapy and no disease evidence was observed for 12 months. In October 2004, ovarian cancer recurred in correspondence of the sixth hepatic segment and mediastinum lymph nodes. Conscious of the elevated risk of a new combined abdominal and thoracic surgery, the patient remained strongly motivated to undergo a further surgical intervention to pursue complete removal of the recurrent lesions. Consequently, the gynecologic oncology surgeon together with the thoracic surgeon performed the fifth cytoreduction, consisting of the dissection of the liver metastasis and the mediastinum lymphadenopathy. Optimal debulking was achieved and the postoperative course proceeded with no complications. Six cycles of carboplatin plus gemcitabine were administered and the patient remained disease-free for 25 months. She recurred for the fifth time in August 2007, reporting rectal disease implants and a presacral lesion. This time she was subjected to 3 cycles of topotecan-based chemotherapy, but with evidence of stable disease, the surgeon and patient decided on a sixth cytoreduction with complete removal of all metastatic lesions. As a postoperative complication, a wound dehiscence was experienced 1 week later and treated with surgical scarification and antibiotic therapy. After recovery, 5 cycles of PEGylated liposomal doxorubicin were administered. Five months later, the patient recurred again with an isolated diaphragmatic lesion. Due to the patient’s will not to be treated with chemotherapy, the diaphragmatic metastasis was successfully surgically removed and the postoperative course was regular, with patient postoperative performance status (PS) 0 reported. Seven months later, new lesions involving the rectum, the piriform muscle, and the aortic lymph nodes occurred. An eighth cytoreduction was consequently carried out and RT <2 was obtained. Five cycles of postsurgical chemotherapy with oxaliplatin were performed but in May 2010 the patient had disease progression. Two further chemotherapy lines, with paclitaxel plus bevacizumab before and carboplatin alone after, were administered, but in July 2011, a ninth cytoreductive surgery was attempted. Disease recurrence involved pelvis and liver. A rectosigmoidal resection, with successive colostomy, and a presacral nodule dissection were performed, but nonoptimal RT was achieved. Postoperative course was complicated by a vesico-vaginal fistula. Ten postoperative cycles of carboplatin-based chemotherapy were given but disease progression occurred in October 2012. Two palliative chemotherapy lines were given: the first one with trabectedin, which resulted in a partial response up to 8 months, and the second one with carboplatin plus paclitaxel, administered for 6 months. Disease progression occurred in May 2014 and the patient died at home in August 2014, 17 years after her advanced ovarian cancer diagnosis and 9 cytoreductive surgeries. Her clinical history is summarized in detail in Table I.

Clinical history and evaluation of the predictive criteria of cytoreducability in a patient who underwent multiple cytoreductive surgeries

Site of disease recurrence PS Ascites Peritoneal carcinomatosis PFI, mo CA125, U/mL Surgery ChT RT, cm Morbidity
CA = carbohydrate antigen; ChT = chemotherapy; GEM = gemcitabine; JM8 = carboplatin; OXL = oxaliplatin; PEC = paclitaxel, epirubicin, cisplatin; PFI = progression-free interval; PS = Performance Status; RT = residual tumor.
aPartial response.
bAbdominal pain and subocclusive symptoms.
cPartial response, subocclusive symptoms.
Diagnosis: May 1997 Peritoneal carcinomatosis (>20 nodules); bilateral ovarian masses; rectosigmoidal serosa nodule; diaphragmatic nodule 0 No Yes - <35 Primary debulking surgery PEC 0 No
Recurrence 1: Feb 1998 Right inguinal lymph nodes 0 No No 3 <35 Laparoscopy; right inguinal lymphadenectomy Topotecan 0 No
Recurrence 2: Jan 2000 Diaphragmatic nodule; liver (III segment); rectosigmoidal serosa nodule 0 No No 17 <35 Diaphragmatic nodule dissection; liver nodule dissection; rectosigmoidal serosa Paclitaxel (weekly) 0 No
Recurrence 3: April 2003 Spleen; para-aortic lymph nodes; periumbilical skin nodule 0 No No 32 <35 Splenectomy; para-aortic lymphadenectomy; periumbilical skin and subcutaneous lesion dissection JM8, paclitaxel (3 weekly) 0 No
Recurrence 4: Oct 2004 Liver (VI segment); mediastinum lymph nodes 0 No No 12 <35 Liver nodule dissection; mediastinal lesion dissection JM8, GEM 0 No
Recurrence 5: Aug 2007 Rectal implants; presacral lesions 0 No No 25 <35 Sacrum surface implants removal; rectal resection; umbilical hernia correction Topotecan (presurgery); Caelyx (postsurgery) 0 Wound dehiscence
Recurrence 6: Mar 2009 Diaphragmatic nodule 0 No No 5 <35 Diaphragmatic nodule dissection No ChT (patient’s desire) 0 No
Recurrence 7: Oct 2009 Right pararectal fossa lesion; piriform muscle 0 No No 7 <35 Piriform muscle nodule dissection; rectal nodule dissection OXL <2 No
Progression: May 2010 Liver; presacral lesion 0 No No 1 <35 Paclitaxel, Avastin (weekly)a
Progression: Jul 2011 Rectum/sacral lesion 1b No 8 <35 Rectosigmoidal resection; presacral nodule; colostomy JM8 >2 Vesico-vaginal fistula
Progression: Oct 2012 Presacral lesion; liver 0 No 10 <35 Trabectedinc; JM8 + paclitaxel No
Progression: May 2014 Widespread abdominopelvic disease 3 No Yes - <35 -

Discussion

To our knowledge, this is the first experience of 9 cytoreductive surgeries in ovarian cancer, with an acceptable rate of complications and a 17-year follow-up.

According to international guidelines, our patient with her first recurrence after only 3 months should be defined as a platinum-resistant ovarian cancer patient, with a less favorable prognosis. Nonetheless, had the second recurrence after more than 17 months. This could be partially explained by the evidence that isolated lymph nodal recurrences when surgically resected have a good prognosis and a longer postrelapse survival (7).

Our patient underwent adjuvant chemotherapy after each surgery, except once. Chemotherapy could have improved the outcome of the surgical effort and the optimal surgical effort might have reduced the presence of drug-resistant cells. Our data are consistent with those of Fotopoulou et al (5), who showed that optimal cytoreduction followed by chemotherapy in recurrent disease has a beneficial impact on survival. On the contrary, it has been recently demonstrated by Hanker et al (8) that no more than 3 chemotherapy lines in management of recurrent disease is beneficial for patients. This led the authors to speculate that in selected patients the integration of surgery before systemic treatment at recurrence could maximize the chemotherapeutic effect in small tumor disease.

Our patient also had other negative prognostic factors: tumor stage, histologic subtype, and the presence of carcinomatosis at initial diagnosis (>20 nodules). Nevertheless, she was optimally debulked at primary surgery and this could explain her good survival, confirming the role of RT as the strongest independent predictor of prolonged survival in primary cytoreduction (9). Postoperative RT retains its strong impact on the overall prognosis also in secondary and tertiary cytoreductive surgery (5). Predictive criteria of tumor resectability at recurrence seem to be PS, RT at previous surgery, absence of ascites according to Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) score, presurgical serum CA125 values, localizations of disease, and treatment-free interval, according to minor reports (9). In our patient, these criteria had an overall favorable presentation for the majority of recurrences, allowing the surgeon to achieve optimal debulking in all except 2 surgeries, with a globally satisfactory complication rate and a good postoperative quality of life reported by the patient. Clinical behavior of ovarian cancer described in our report suggests BRCA mutated or BRCAness ovarian neoplasia. We do not have any certainty on the BRCA status of our patient because she could not perform the genetic text due to her negative family history.

Waiting for the results of randomized trials (Study Comparing Tumor Debulking Surgery Versus Chemotherapy Alone in Recurrent Platinum-Sensitive Ovarian Cancer [DESKTOP III] and Carboplatin + Paclitaxel w/wo Bevacizumab After Surgery [GOG 213]), and even if we are aware that multiple surgeries should not be considered as the standard treatment for recurrent ovarian cancer, surgery might represent a useful tool in adjunct to chemotherapy in the management of selected patients with epithelial ovarian cancer, but should be performed by highly specialized gynecologic oncologists (10). A deeper knowledge of biological assessment of epithelial ovarian cancer will allow an easier interpretation of ovarian cancer behavior. Global preoperative assessment and nutritional status evaluation might play a role in the decision-making process. Furthermore, clinical trials investigating the best imaging procedure for the preoperative assessment of ovarian cancer recurrence are strongly encouraged.

Disclosures

Financial support: None.
Conflict of interest: None.
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Authors

Affiliations

  • Department of Obstetrico-Gynecological and Urologic Sciences, “Sapienza” University of Rome, Rome - Italy

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