A Prospective Outcomes Analysis of Palliative Procedures Performed for Malignant Intestinal Obstruction Due to Recurrent Ovarian Cancer

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1 The Oncologist Gynecologic Oncology A Prospective Outcomes Analysis of Palliative Procedures Performed for Malignant Intestinal Obstruction Due to Recurrent Ovarian Cancer DENNIS S. CHI, a REBECCA PHAËTON, b THOMAS J. MINER, c STEVEN V. KARDOS, d JOHN P. DIAZ, a MARIO M. LEITAO,JR., a GINGER GARDNER, a JAE HUH, a WILLIAM P. TEW, e JASON A. KONNER, e YUKIO SONODA, a NADEEM R. ABU-RUSTUM, a RICHARD R. BARAKAT, a DAVID P. JAQUES f a Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, USA; b Department of Obstetrics and Gynecology, Hospital of University of Pennsylvania, Philadelphia, Pennsylvania, USA; c Department of Surgery, Brown University, Providence, Rhode Island, USA; d George Washington University School of Medicine, Washington, DC, USA; e Solid Tumor Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA; f Washington University, St. Louis, Missouri, USA Key Words. Palliative surgery End-of-life care Recurrent gynecologic cancer Disclosures: Dennis S. Chi: Honoraria: Genzyme; Rebecca Phaëton: None; Thomas J. Miner: None; Steven V. Kardos: None; John P. Diaz: None; Mario M. Leitao, Jr.: None; Ginger Gardner: None; Jae Huh: None; William P. Tew: None; Jason A. Konner: None; Yukio Sonoda: Honoraria: Genzyme; Nadeem R. Abu-Rustum: None; Richard R. Barakat: None; David P. Jaques: None. The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer reviewers. ABSTRACT Objective. To obtain prospective outcomes data on patients (pts) undergoing palliative operative or endoscopic procedures for malignant bowel obstruction due to recurrent ovarian cancer. Methods. An institutional study was conducted from July 2002 to July 2003 to prospectively identify pts who underwent an operative or endoscopic procedure to palliate the symptoms of advanced cancer. This report focuses on pts with malignant bowel obstruction due to recurrent ovarian cancer. Procedures performed with an upper or lower gastrointestinal (GI) endoscope were considered endoscopic. All other cases were classified as operative. Following the procedure, the presence or absence of symptoms was determined and followed over time. All pts were followed until death. Results. Palliative interventions were performed on 74 gynecologic oncology pts during the study period, of which 26 (35%) were for malignant GI obstruction due to recurrent ovarian cancer. The site of obstruction was small bowel in 14 (54%) cases and large bowel in 12 (46%) cases. Palliative procedures were operative in 14 (54%) pts and endoscopic in the other 12 (46%). Overall, symptomatic improvement or resolution within 30 days was achieved in 23 (88%) of 26 patients, with 1 (4%) postprocedure mortality. At 60 Correspondence: Dennis S. Chi, M.D., 1275 York Ave, Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Telephone: ; Fax: ; gynbreast@mskcc.org Received March 23, 2009; accepted for publication July 15, 2009; first published online in The Oncologist Express on August 14, AlphaMed Press /2009/$30.00/0 doi: /theoncologist The Oncologist 2009;14:

2 836 Palliative Care in Ovarian Cancer days, 10 (71%) of 14 pts who underwent operative procedures and 6 (50%) of 12 pts who had endoscopic procedures had symptom control. Median survival from the time of the palliative procedure was 191 days (range, ) for those undergoing an operative procedure and 78 days (range, ) for those undergoing an endoscopic procedure. Conclusion. Patients with malignant bowel obstructions due to recurrent ovarian cancer have a high likelihood of experiencing relief of symptoms with palliative procedures. Although recurrence of symptoms is common, durable palliation and extended survival are possible, especially in those patients selected for operative intervention. The Oncologist 2009;14: INTRODUCTION As the surgical treatment of gynecologic cancer becomes more sophisticated and chemotherapeutic approaches become more effective, patients prognoses have improved with respect to the duration of their disease-free state. However, when cancer does recur and effective treatment options have been exhausted, the focus of management shifts from curative intent to palliation of symptom manifestations. The surgical literature is replete with investigations that attempt to analyze, improve, and provide management recommendations for patients with newly diagnosed gynecologic malignancies. However, palliative care guidelines, specifically as they pertain to surgical options, remain less well defined. Ideally, the surgeon should be able to counsel patients and their families regarding the risks of surgical procedures or, more importantly, prognosticate based on data rather than speculations or anecdotal experience [1]. The need for a formal definition of palliative surgery has been visited by the Institute of Medicine, which stated that palliative care should become an area of expertise, education, and research that should be redefined to include prevention as well as relief of symptoms [2]. In a survey of practicing surgical oncologists, when asked to delineate the qualifications of what constitutes a palliative procedure, the wide variety of interpretations brought to light the need to embrace a more formal definition and expansion of identification of procedures performed with this intent [3]. In the broadest definition, palliative care should encompass those operations, procedures, and/or therapy performed with the goal of improving quality of life, relieving symptoms, or controlling pain. The success of a palliative intervention should be determined by patient report of quality and duration of symptom improvement [4]. Palliative cancer therapy first begins with the physician realizing that the disease is incurable and the patient coming to the realization that treatment risks such as severe doselimiting toxicity, postoperative complications, and treatment-related death may no longer be acceptable. Furthermore, the patient s functional reserve must be assessed prior to offering a treatment modality, as the ability, not only to undergo, but also to successfully recover from an intervention are major determinants of subsequent quality of life. Although there is continued increase in the integration of palliative approach into practice, clinical data guiding care still need to be gathered to add to further evidence-based practice. At this juncture, a surgeon discussing a palliative procedure with a patient therefore relies on clinical experience, personal gestalt, patient desire, and the paucity of data. The goal of this study was to obtain prospective outcomes data on patients undergoing palliative operative or endoscopic procedures for malignant bowel obstruction due to recurrent ovarian cancer. MATERIALS AND METHODS This study was derived from a previous publication that analyzed all palliative procedures performed at our institution between July 1, 2002 and June 30, 2003 [5]. Whereas the prior publication reported on all procedures performed during the study period, this analysis focuses on those patients with recurrence of ovarian cancer. As stated in the previous report, the operating room and endoscopy suite schedules were screened on a daily basis to identify all operative and endoscopic cases performed for symptomatic management of metastatic or advanced cancer. Procedures performed in these patients were defined by intent as either nonpalliative or palliative. Cases were identified as palliative when either the medical record documented palliative intent or when interview of the surgeon confirmed the intent to relieve symptoms, control pain, or improve the quality of life. Inclusion criteria for this study included the performance of a palliative procedure for malignant bowel obstruction due to recurrent ovarian cancer, confirmed by either explicit report in the operative dictation or by interviews of the surgeon. The demographic information of the patient, chief complaint, and prior treatment history were collected on all patients. ECOG (Eastern Cooperative Oncology Group) level, NCI (National Cancer Institute) fatigue scale, albumin, hemoglobin, and type of palliative procedure were also obtained.

3 Chi, Phaëton, Miner et al. 837 Table 1. Patient characteristics Variable No. n 26 Age (years) Median 54 Range ECOG performance status 0 1 (4%) 1 21 (81%) 2 2 (7.5%) 3 2 (7.5%) NCI fatigue scale 0 5 (19%) 1 15 (58%) 2 3 (11.5%) 3 3 (11.5%) Unplanned weight loss Yes 8 (31%) No 18 (69%) Hemoglobin (g/dl) Median 10.6 Range Serum albumin (g/dl) Median 3.4 Range Site of obstruction Small intestine 14 (54%) Large intestine 12 (46%) Palliative procedure PEG tube 8 (31%) Colonic stent 4 (15%) Intestinal bypass/resection 6 (23%) Ileostomy 2 (8%) Colostomy 6 (23%) Abbreviations: PEG, percutaneous endoscopic gastrostomy. All patients had complete initial symptom assessment. Symptoms of gastrointestinal obstruction included persistent nausea/vomiting, abdominal distention, abdominal pain, and unplanned weight loss. The presence or absence of these subjective symptoms after palliative intervention was determined and followed over time. When a patient was unable to describe a symptom and subjective evidence was not available, a patient was considered to have a specific symptom if a finding on radiographic, endoscopic, laboratory, or physical exam documented a finding consistent with and related to the original complaint. Patients who required narcotic pain relief for greater than 30 Table 2. Procedures performed and outcomes Procedure No. of patients Symptom improvement or resolution within 30 days Grade 3 5 complication PEG 8 6 (75%) 2 (25%) Colonic stent 4 3 (75%) 1 (25%) Intestinal 6 6 (100%) 0 (0%) bypass/ resection Ileostomy 2 2 (100%) 1 (50%) Colostomy 6 6 (100%) 0 (0%) Total (88%) 4 (15%) Abbreviations: PEG, percutaneous endoscopic gastrostomy. days were treated by a pain specialist, or who complained of pain in a location compatible with their presenting clinical complaint on more than two outpatient clinic visits were classified as having clinically significant pain. Weight loss was defined as unplanned loss greater than 10 pounds over a 90-day period. In addition to assessment of symptom-free interval, data on frequency and complications were compiled. A previously defined grading scale for classification of surgical complications was used to define the severity of secondary surgical events within the 30 days of the palliative procedure [6]. Of the patients who had more than one complication, the higher-grade complication was assigned. Further surgical, medical, or radiation therapy to manage new or recurrent symptoms was also recorded. Evidence of symptom resolution and/or the development of new symptoms was collected from the patient record. In this study, all patients were followed until death. RESULTS During the study period, a total of 1,022 palliative operative or endoscopic procedures were performed at our institution. Of these 1,022 cases, 81 (7%) were performed on gynecologic oncology patients. After careful review, palliative intent could not be verified by review of the medical records in 7 patients, leaving 74 evaluable patients. Of these 74 evaluable palliative procedures, 16 were performed for urologic obstructions, 16 for gastrointestinal (GI) sequelae of nonovarian malignancies, 9 for neurologic symptoms, 4 for respiratory compromise, and 3 for other reasons. This left 26 (35%) palliative procedures performed for malignant GI obstruction due to recurrent ovarian cancer and these 26 cases formed our study cohort.

4 838 Palliative Care in Ovarian Cancer Table 3. Type of procedure and symptom recurrence Type of procedure No. of patients Symptom recurrence or death within 60 days Endoscopic 12 6 (50%) 7 (58%) Operative 14 4 (29%) 5 (36%) Total (38%) 12 (46%) Symptom recurrence or death within 90 days The median age of the 26 patients was 54 years (range, 22 81). The median number of prior surgical procedures in the management of their ovarian cancers was 2 (range, 1 2). The median number of prior chemotherapeutic regimens was 5 (range, 1 10). All 26 patients presented with one or more symptoms of bowel obstruction. Table 1 outlines the other patient characteristics at presentation and palliative procedures performed. Most patients had an ECOG performance status of 1, NCI fatigue scale value of 1, and no unplanned weight loss. The majority of patients were anemic, with a median hemoglobin of 10.6 g/dl, and hypoalbuminemic, with a median serum albumin of 3.4 g/dl. Only 3 patients had a hemoglobin level of 12 g/dl or greater and only 2 patients had a serum albumin of 4.0 g/dl or greater. The site of obstruction was the small bowel in 14 (54%) cases and large bowel in 12 (46%) cases. Palliative procedures were operative in 14 (54%) patients and endoscopic in the other 12 (46%). Overall, symptomatic improvement or resolution within 30 days was achieved in 88% (23/26) of patients (Table 2). Median hospital stay was 11 days (range, 1 43). There were three grade 3 complications and one death (grade 5) due to progression of disease within 30 days of the palliative procedure. After the palliative procedure, 17 (65%) of the 26 patients went on to receive salvage chemotherapy. Chemotherapy was given to 12 (86%) of the 14 patients who underwent operative procedures and 5 (42%) of the 12 women who had endoscopic procedures. At 60 days after the palliative procedure, recurrence of the primary symptoms or death occurred in 10 (38%) of the 26 patients (Table 3). By 90 days, recurrence of symptoms or death occurred in 12 (46%) of the 26 patients. Interestingly, 9 (64%) of the 14 patients treated with an operative procedure had symptom control greater than 90 days after the surgery. Median survival from the time of the palliative procedure was 191 days (range, ) for those undergoing an operative procedure and 78 days (range, ) for those undergoing an endoscopic procedure. DISCUSSION There is continued need for research and education with regard to end-of-life care. A review of articles published in the Journal of Clinical Oncology reveals that pain or symptoms are analyzed in less than 5% of phase II and III trials [7]. Palliative care is an approach that improves the quality of life of patients and their families facing the problem associated with life-threatening illness, through the prevention and relief of suffering by early identification and impeccable assessment and treatment of pain and other problems physical, psychosocial, and spiritual [8]. This statement, as defined by the World Health Organization Research, summarizes the goals of end-of-life care. Further research and efforts are needed to educate physicians, comfort families, guide patients, and remove limitations on the possibilities of treatment options during end-of-life care. Patients prefer treatment options based on their values and understanding of the risks and benefits associated with choice of treatment. Therefore, without further study there remains a variety of clinical practices when recurrent disease finds a patient at the end of life. Despite the fluency of the existing literature, most studies performed have been retrospective in nature. In a review of the literature by Miner et al., 348 articles were identified as addressing surgical palliation. Of those articles, 72% were retrospective, 10% were review articles, 9% were case reports, and 9% were prospective in nature [9]. This study initiates the much-needed report of data and analysis that will guide physicians in the future who are limited by the absence of clear recommendations of standards of care and will improve concrete evidence that may assist patients and their families in deciding for or against procedures. As stated previously, this study was derived from previously reported clinical data that reviewed all palliative procedures performed at our institution and focuses on those patients with recurrence of ovarian cancer. The rationale of distilling out the palliative procedures specifically for ovarian cancer is one of the strengths of this study in that the patient population was very homogenous, allowing for a more reliable assessment of symptom im-

5 Chi, Phaëton, Miner et al. 839 provement. Our data demonstrated symptoms can be palliated in close to 90% of patients; counseling on their options should be provided to patients during the end-of-life period. Approximately half of the patients will have recurrence of their symptoms within 3 months of the procedure. Although patients who have an operative procedure may have prolonged symptom control and extended survival compared with those having endoscopic procedures, almost all patients will eventually succumb to their disease within 1 year. These findings are similar to those reported previously from our institution and others [10 13]. One of the weaknesses of this study is that although key questions and data may have been addressed, the small sample size may have precluded the ability to detect statistically significant outcomes. This study was designed to prospectively follow patients who were already scheduled for procedures and the palliative nature of the intervention was then determined. As future research in this setting is undertaken, larger studies are needed including all patients REFERENCES 1 Easson, Alexandra M, Librach SL. Discussion of death and dying in surgical textbooks. Am J Surg 2001;182: Field MJ, Cassell CK. Approaching Death-Improving Care at the End of Life. Washington, DC, National Academy Press, McCahill LE, Krouse R, Chu D, et al. Indications and use of palliative surgery: results of Society of Surgical Oncology survey. Ann Surg Oncol 2002;9: Porzsolt F. Goals of palliative cancer therapy. J Clin Oncol 1993;11: Miner TJ, Brennan MF, Jaques DP. A prospective, symptom related, outcomes analysis of 1022 palliative procedures for advanced cancer. Ann Surg 2004;240: ; discussion Martin RC 2nd, Jaques DP, Brennan MF et al. Achieving R0 resection for locally advanced gastric cancer: is it worth the risk of multiorgan resection? J Am Coll Surg 2002;194: who are terminal and at the end of life who can then be followed to determine if palliative interventions offer more effective palliation of symptoms than simple supportive care. Until that time, the final determination of the success of palliative care practices remains with patient perceptions of the quality of care received in the end-of-life period. ACKNOWLEDGMENTS Presented at the Society of Gynecologic Oncologists 37th Annual Meeting in Palm Springs, CA, March 22 26, AUTHOR CONTRIBUTIONS Conception/design: Dennis S. Chi, Thomas J. Miner Finanical support: Richard R. Barakat, David P. Jaques Administrative support: Jae Huh, Richard R. Barakat, David P. Jaques Provision of study materials or patients: Thomas J. Miner, Ginger Gardner, Richard R. Barakat, David P. Jaques Collection/assembly of data: Rebecca Phaëton, Thomas J. Miner, Steven V. Kardos, Jae Huh, Yukio Sonoda, Nadeem R. Abu-Rustum Data analysis and interpretation: Dennis S. Chi, Rebecca Phaëton, Steven V. Kardos, Ginger Gardner, William P. Tew, Jason A. Konner, Yukio Sonoda, Nadeem R. Abu-Rustum Manuscript writing: Dennis S. Chi, John P. Diaz, Mario M. Leitao, Jr. Final approval of manuscript: Dennis S. Chi, Mario M. Leitao, Jr., William P. Tew, Jason A. Konner, Yukio Sonoda, Nadeem R. Abu-Rustum, Richard R. Barakat, David P. Jaques 7 Prozsolft F. Goals of palliative cancer therapy. J Clin Oncol 1993;11: World Health Organization. Palliative Care. Available at: who.int/cancer/palliative/en, accessed August 4, Miner TJ, Jaques DP, Tavaf-Motamen H, et al. Decision making on surgical palliation based on patient outcome data. Am J Surg 1999;177: Feuer DJ, Broadley KE, Shepherd JH et al. Surgery for the resolution of symptoms in malignant bowel obstruction in advanced gynaecological and gastrointestinal cancer. Cochrane Database Syst Rev 2000;(4):CD Pothuri B, Vaidya A, Aghajanian C et al. Palliative surgery for bowel obstruction in recurrent ovarian cancer: an updated series. Gynecol Oncol 2003;89: Pothuri, B, Montemarano, M, Gerardi, M et al. Percutaneous endoscopic gastrostomy tube placement in patients with malignant bowel obstruction due to ovarian carcinoma. Gynecol Oncol 2005;96(2): Caceres A, Zhou Q, Iasonos A et al. Colorectal stents for palliation of large bowel obstruction in recurrent gynecologic cancer: an updated series. Gynecol Oncol 2008;108: