bowel obstruction in advanced or recurrent ovarian cancer

Bowel Obstruction in Bowel Obstruction in Advanced or Recurrent Advanced or Recurrent Ovarian CancerOvarian Cancer

Ming-Shyen Yen M.D.Chief, Division of Gynecology

Department of Obstetrics and GynecologyTaipei Veterans General Hospital

National Yang-Ming University

The 6th Chinese Conference on Oncology

The 9th Cross-strait Academic Conference on Oncology

May, 21, 2010

台北榮民總醫院Taipei Veterans General Hospital 主講：張文瀚

title

台灣男女性十大癌症 台灣男女性十大癌症 (95(95 年年 ))

Age-standardized incidence of top 10 cancers for females over a 5-year period (2002-2006)

Age-standardized mortality rate for top 10 cancers for females over a 5-year period (2003-2007)

Breast and Malignancies of Breast and Malignancies of Female Genital Tracts in Taiwan Female Genital Tracts in Taiwan

(2006)(2006)No. of new cases No. of deaths

Breast 6895(49.99)* 1439(10.41)*

Cervix (invasion)

1828(13.18)* 792(5.61)*

Corpus 1159(8.45)* 135(1.00)*

Ovary 1000(7.47)* 380(2.78)*

Others 117(0.83)* 39(0.27)*

Total 10999(79.92)* 2785(20.07)*

*age-adjusted incidence per 100,000 women

台灣歷年卵巢癌症發生率 (一 )

1336

2122

988

803

85年~95年上皮性卵巢癌型態分佈圖

Mucinous

Serous

EM

Clear

(25.5﹪)

(40.4﹪)

(18.8﹪)

(15.3﹪)

TOTAL ：5249

台灣歷年卵巢癌症發生率 ( 二 )

Ovarian CancerOvarian Cancer

Patterns of Spread:1. Direct extension to adjacent

organs2. By exfoliation and dissemination of

clonogenic tumor cells throughout the peritoneal cavity

3. Via lymphatic system

General Treatment Strategy for General Treatment Strategy for Ovarian CancerOvarian Cancer

Cytoreductive Surgery Chemotherapy Therapy for relapse :

Secondary debulking 2nd-line chemotherapy Intraperitoneal chemotherapy IP P32

Whole-abdominal radiation (WAR)

Patterns of RecurrencePatterns of Recurrence

Serologic relapse Rising CA-125 only evidence of disease

Localized recurrenceDisseminated intraperitoneal

diseaseExtraperitoneal metastasesRecurrences can be symptomatic

or asymptomatic

Treatment ConsiderationsTreatment Considerationsin Recurrent Ovarian Cancerin Recurrent Ovarian Cancer

Goals of therapy Palliate symptoms Prevent symptom development Maintain quality of life Increase progression-free survival Prolong overall survival

Therapeutic Goals in Recurrent Therapeutic Goals in Recurrent Ovarian CancerOvarian Cancer

Manage symptomatic patientsDelay progression of disease

PFSIncrease survivalMaintain quality of life

Controversies in Recurrent Controversies in Recurrent Ovarian CancerOvarian Cancer

Management of an asymptomatic rise in CA-125 in patients without evidence of disease on CT scan or on physical examination

Role of secondary cytoreductionOptimal chemotherapy

Platinum-sensitive diseasePlatinum-resistant diseaseUse of in vitro sensitivity resistance assaysDetermine length of treatment

Role of biologic/targeted therapy

Chemotherapy Principles in Chemotherapy Principles in Recurrent Ovarian CancerRecurrent Ovarian Cancer

Multiple agents have clinical activityActivity superior in platinum-sensitive patients

Combinations are superior to single-agent platinum in platinum-sensitive patients

No established role for combinations in platinum-resistant disease

Management considerations Length of treatment and “drug holidays” Choice of combination in platinum-sensitive

patients Choice of drug in platinum-resistant patients

Surgical Management of Surgical Management of Recurrent Ovarian CancerRecurrent Ovarian CancerSecondary cytoreductive surgery

The standard management of patients with recurrence, particularly the role of surgery, remains poorly defined because of the absence of prospective randomized data. (wait GOG #213)

The longer the PFI, or the less residual disease after primary treatment, the better the patient’s performance status, the more likely that the patient will benefit from 2nd cytoreductive surgery.

Palliative surgeryThe most common indication is malignant intestinal

obstruction.The management of malignant obstruction is

challenging, not only because it usually occurs in the setting of recurrent, often drug-resistant, but also because there is a high morbidity and mortality associated with surgery.

JCO, 25:2873-2883, 2007

Criteria for Consideration of Secondary Cytoreductive Surgery (SCRS)

Eisenkop SM et al. Cancer 2000; 88: 144.

Complete clinical response with a disease-free interval ≥6 months

Rising CA125 level and/or radiographic or physical findings suggestive of recurrence

Absence of unresectable extra-abdominal or hepatic metastases

Patient acceptance of post-SCRS adjuvant therapy

Absence of medical contraindications to SCRS

Performance status score ≤3

Secondary Cytoreductive SurgeryRoyal Hospital for Women, U.K.

Survival Benefit - Risk Ratio Analysis

Tay EH et al. Obstet Gynecol 2002; 99: 1008.

AGO DESKTOP- I OVAR Study: Surgery in AGO DESKTOP- I OVAR Study: Surgery in Recurrent Ovarian Cancer Recurrent Ovarian Cancer (retrospective)(retrospective)

Arbeitsciemeinschaft Gynakologische Onkologie Ovarian Cancer Study Group

Harter P, et al, Ann Surg Oncol. 2006

2000-2003 N= 267

Median survival 45.2 vs. 19.7 mos

Hazard Ratio (HR)= 3.71; 95% CI 2.27-6.05; P < 0.0001.

No residual

Residual > 10mm

Residual 1-10mm

Role of Surgery in Ovarian Role of Surgery in Ovarian CancerCancer Category I Surgery:

Initial surgical cytoreduction Interval surgical cytoreduction Cytoreduction after neoadjuvant

chemotherapy

Category II Surgery: 2-look surgical reassessment Extent-of-disease surgical reassessment Secondary cytoreduction Palliative surgery

Surgery for palliationSurgery for palliation

Palliative surgery combined with local

irradiation: Cutaneous lesion:

Supraclavicular or inguinal-node metastasis Abdominal wall metastasis

Resection of an involved organ: Liver, brain, lung to relieve pain or improve

function

Surgery considered to relieve obstruction of

the urinary tract or intestine

The most common problem:

“ Intestinal Obstruction ”

Malignant Bowel Obstruction Malignant Bowel Obstruction (MBO)(MBO) MBO is a complex problem occurring particularly in cancer patients with advanced gynecological and gastrointestinal cancer

1. Epidemiology:

Ovarian cancer – 5.5 to 42%

Colorectal cancer – 4.4 to 24%

Breast cancer, lung cancer, melanoma – 3 to 15%

2. Etiology:

Benign – adhesions, radiation enteritis

Malignant – single site, multiple sites, diffuse disease

3. Considerations:

Single site vs Multiple sites Partial vs Complete Small intestine vs Large intestine

Bowel Obstruction in Advanced Bowel Obstruction in Advanced or Recurrent Ovarian Canceror Recurrent Ovarian Cancer

Epidemiology: Exact incidence: unknown Retrospective studies: 20 – 50 % Related to disease and result of prior

therapy Incidence from causes other than cancer: 5

– 24 %

Bowel Obstruction in Advanced Bowel Obstruction in Advanced or Recurrent Ovarian Canceror Recurrent Ovarian Cancer

Etiology:Progressive intra-abdominal tumor growth that

leads to extrinsic occlusion of bowel lumen

Intraluminal occlusion due to pelvic recurrences or mesenteric or omental masses

Intestinal motility problems with functional obstruction due to the infiltration of the mesentery or bowel muscle and nerves (extensive intraperitoneal carcinomatosis)

Result of prior therapy : adhesion from prior previous surgery, IP C/T,

or R/T

Damage of intestinal epithelium

Bowel inflammatory response with edema, hyperemia and production of PG,VIP,nociceptive mediators

Partial or complete bowel obstruction ↑ Bowel contractions to

surmount the obstacle

↑ Colicky pain

Nausea and/or vomiting

Reduction or stop of through-movements of intestinal contents

Continuous pain Distension, Tumor mass, Hepatomegalia

Causes of Symptoms in MBOCauses of Symptoms in MBO

Bowel distension lumen contents

Gut epithelial surface area

Bowel secretions of H2O,Na,Cl

Bowel Obstruction in Advanced Bowel Obstruction in Advanced or Recurrent Ovarian Canceror Recurrent Ovarian Cancer

Diagnosis: History Clinical symptoms Physical findings Supine and upright X-ray Radiographic contrast of the small and/or large

intestine Abdominal CT scan Ultrasound

Management of Patients with Management of Patients with MBOMBO Influenced by :

Level of obstruction Pattern of disease Clinical stage of cancer related to prognosis Prior anticancer treatments Patient’s health

One of the most challenging clinical scenarios

Balancing the advantages and disadvantages of intervention with :

Their prognosis Tumor biology Quality of life

Management of Patients Management of Patients with MBOwith MBODiagnosis and Initial ManagementProblems with the Literature

When Not to operate: MBO form Generalized CarcinomatosisSurgical Decision-Making in MBO :

Patient factorsDisease factorsOperative facotrsOther treatment approaches

Stenting Percutaneous decompression

Decision-Making in Palliative Care

Management of Patients with Management of Patients with MBOMBO

Patient presenting with symptoms of bowel obstruction and a history of cancer

Decision-making with patient and family

Surgical decision making Technical factorsPatient factors

Clinical assessment• Patient acutely ill: surgical emergency. Most patients with MBO ≠ surgical emergency

• History of symptom

Radiology assessment : CT +/- MRI

• Diagnosis and cause of obstruction• Site: single vs multiple

Large vs small bowel Partial (Most MBO) vs complete

Management of Patients with Management of Patients with MBOMBO

Patient factors Technical factors Age : biologic / physiologic Performance status Stage of cancer: previous treatments, any anticancer treatment options Malnutrition / cachexia Concurrent illness Ascites

Degree of invasivenessInterventional radiologyEndoscopyOpen laparotomy / laparoscopy

Anesthetic requirements Risk of post-procedure complications

Management of Patietns with Management of Patietns with MBOMBO

Surgical decision making : Identify the symptom Identify a surgical cause for the symptom: mechanical mechanical vs functional obstructionfunctional obstruction Assess the realistic ability of an intervention to alleviate the

symptom Formulate recommendations: No obligation to recommend futile therapy

Decision-making with patient and family : What do they understand about the disease? What do they expect from the surgery? Explain clearly the expected potential benefits of the

intervention: Is this something that would be worth it to them given

the risks? Does this procedure fit with the goals of care?

Bowel Obstruction in Advanced Bowel Obstruction in Advanced or Recurrent Ovarian Canceror Recurrent Ovarian Cancer

Conservative treatment: Nasogastric tube drainage Intravenous fluid hydration Medical management: hyoscine butybromide, haloperidol, corticosteroids, somatostatin, morphine, parenteral nutrition for perioperative

period Percutaneous endoscopic gastrostomy (PEG) Stents

Pharmacological treatment Pharmacological treatment

in inoperable MBOin inoperable MBODrugs to control nausea and vomiting in

MBO

Somatostatin analogue

Octreotide 0.2-0.9 mg/day SC

Anticholingergic drug

Hyoscine butylbromide 40-120 mg/D SC,IV or Hypscine hydrobromide 0/8-2.0 mg/D SC or Glycopyrrolate 0.1-0.2 mg t.i.d SC or IV

and/or

Prokinetic drug

Metoclopramide 60-240 mg/D SC in p’ts with partial occlusion and no colic

Neuroleptic drug

Haloperidol 5-15mg/D SC or Methotrimeprazine 6.25-50 mg/D SC or Prochlorperazine 25mg 8h PR or Chlopromazine 50-100 mg 8h PR or IM

Antihistamine drug

Cyclizine 100-150 mg/D 8h PR or Dimenhydrinate 50-100 mg SC prn

or

Antisecretory drugsAntiemetics

Indications Problems

Antiemetics Symptom control

Metoclopramide

Functional subobstruction

Stop in definitive or complete obstructionSteroids Subobstructive

statesSymptom control

Hyoscine Symptom control

Octreotide Subobstructive states

Symptom control

Short-term NG Pts unresponsive to pharmacological treatment

Temporary measure

Uncomfortable for long-term use

Indications for the use of symptomatic drugs

Pharmacological treatment Pharmacological treatment in inoperable MBOin inoperable MBO

Bowel Obstruction in Advanced Bowel Obstruction in Advanced or Recurrent Ovarian Cancer (I)or Recurrent Ovarian Cancer (I)

Conservative treatment Percutaneous endoscopic gastrostomy (PEG) :

Symptomatic relief from a NG tube, not necessary for PEG

Only to patients with symptoms poorly controlled with medications and to those who are not imminently

dying Ascites as a relative contraindication, but no adverse

events if ascites draine-out before placement of the PEG

Conservative treatment Stents :

Self-expanding metallic stent via fluoroscopy with or without

endoscopyPalliation for patients with single colonic obstruction

in the left colonVarying degrees of success for gastrodudenal,

duodenal, and small bowel obstruction from malignant disease

No good published criteria to aid in the decision to stent on patients with MBO

The choice of treatment depending on patient factors, tumor factor, and a history of any surgery and/or treatment

Bowel Obstruction in Advanced Bowel Obstruction in Advanced or Recurrent Ovarian Cancer or Recurrent Ovarian Cancer (II)(II)

Bowel Obstruction in Advanced or Bowel Obstruction in Advanced or Recurrent Ovarian Cancer (III)Recurrent Ovarian Cancer (III)

Goal of treatment: Palliative rather than curative measures Improving the QoL with a limited life

expectancy Decision to attempt surgery: Extremely

difficulty Considered:

Successful palliation Risk of repeat obstruction QoL after the surgery Ability for further chemotherapy Rates of operative morbidity and mortality Obstipation vs constipation ?

Bowel Obstruction in Bowel Obstruction in Advanced or Recurrent Advanced or Recurrent Ovarian CancerOvarian Cancer

Types of procedure:Depending on intra-operative findings at surgeryOptions included both intestinal bypass and

resectionPoor characteristics of ideal surgical

candidates: Bulky carcinomatosis Rapidly progressive disease Multiple sites of obstruction Poor performance status Heavy treatment of multiple chemotherapy

agents or radiation therapy Massive ascites?

Management for intestinal obstruction

Bowel Obstruction in Bowel Obstruction in Advanced or Recurrent Advanced or Recurrent Ovarian CancerOvarian Cancer

Successful palliative surgery defined: Survival > 60 days from surgery

Peri-operative mortality defined: Death within 30 days

Operative morbidity: 7 - 64 %Operative mortality: 4- 32 %Median survival: 5 - 33 weeks

Heterogeneous More dependent on response to chemotherapy

than the surgery itself

Bowel Obstruction in Bowel Obstruction in Advanced or Recurrent Advanced or Recurrent Ovarian CancerOvarian Cancer

A through discussion with the patient and her

family

No prospective randomized trial in this

setting

No strict, clear-cut guidelines for

management

The most challenging decisions, and the

decision to operate in gynecologic oncologist

Reoperative Surgery for MBOPreoperative Consideration ( I )

Distorted Anatomy and Loss of Normal Tissue PlanesA thorough knowledge of normal anatomyDepending on the prior surgery – distored fascial

planes, thick adhesions, walled-off fluid collections, a Gordian knot-like configuration of small bowel, and ectopic positions of ureters

A thorough review of the prior operative reportsKnowledge of any prior postoperative complications

Potential Pitfalls and ComplicationsTiming of reoperative surgeryEnterotomies -- only one possible complicationNutrition Immuno-supplements -- enteral feeding, formulas rich in

arginine, glutamine, and omega-3 fatty acids

Reoperative Surgery for MBO Preoperative Consideration ( II )

Preoperative Adjuncts A thorough knowledge of prior surgeries and postoperative courses Tumor markers and additional preoperative

imaging studies Place bilateral ureteral stents routinely

Operative Technique Positioning of the patient Dilators or other long blunt instrument be

placed transvaginally Exposure in visualizing anatomy and

proceeding safely through the exploration Enter the peritoneal cavity in virgin territory

Reoperative Surgery for MBO Preoperative Consideration ( III ) Literature review and retrospective

studies:Patients received benefits in both survival and QoL when operation is chosen and successful for MBO.When pursuing surgical exploration, it is important

to keep in mind all of the different options, including bowel resection with anastomoses, intestinal bypass, creation of stoma, lysis of adhesions, placement of gastrostomy or jejunostomy tubes, or any combination of these.

Unfortunately, there are times that carcinomatosis is so extensive that the only option is to open and close in order to avoid extensive iatrogenic injury.

Multiple authors have tried to define parameters to help determine which patients will likely benefit from palliative surgical intervention.

270 patients with epithelial ovarian cancer (1984 – 2005)

75 patients (28%) developed bowel obstruction

University of Brescia, Venice, Italy

• Age

• Nutritional status

• Tumor spread

• Presence of ascites

• Type

• Previous chemotherapy

• Previous radiation therapy

<< Krebs score >>

This score system benefit from surgical intervention, 1983

Bowel Obstruction and Survival in Bowel Obstruction and Survival in Patients with Advanced Ovarian Patients with Advanced Ovarian CancerCancer

Parameters 0 1 2

Age < 45 45 - 65 > 65

Free interval y (from Dx to onset)

> 2 1 - 2 < 1

Hematocrit %

> 30 25 - 30 < 25

Albumin g/dL

> 3.06 2.55 – 3.06 < 2.55

Lymphocytes cell/mm3

< 1350 < 1125 < 900

Analysis of Prognostic Variables

Bowel Obstruction and Survival in Bowel Obstruction and Survival in Patients with Advanced Ovarian Patients with Advanced Ovarian CancerCancer

Parameter 0 1 2

Weight change%

< 10 10 - 25 > 25

Performancestatus (PSK)

> 80 60 - 70 < 60

Previous operations

Standard Others None

Previous R/T None R/T to pelvis R/t to abdomen

Previous C/T None Single drug Multiple drugs

Analysis of Prognostic Variables

Parameters 0 1 2

Tumor status NO palpable

Palpable Distant

Ascites, L 0.1 - 1 1.1 - 3 > 3

Site of obstruction Large bowel

Small bowel Both

Vomiting No Occasional Persistent

Pain No - Yes

Analysis of Prognostic Variables

Bowel Obstruction and Survival in Bowel Obstruction and Survival in Patients with Advanced Ovarian Patients with Advanced Ovarian CancerCancer

15 Prognostic parameters

New score

G O 89, 2003: 306-311

MSKCC 1994 - 1999

Palliative surgery for bowel Palliative surgery for bowel obstruction in recurrent ovarian obstruction in recurrent ovarian cancercancer

Survival based on successful palliation

Survival based on postoperative chemotherapy

Palliative surgery for bowel Palliative surgery for bowel obstruction in recurrent ovarian obstruction in recurrent ovarian cancercancer

Comparison of survival by type of obstruction

Palliative surgery for bowel Palliative surgery for bowel obstruction in recurrent ovarian obstruction in recurrent ovarian cancercancer

Survival based on whether surgical correction is possible

Survival based on whether surgical correction is possible, successful palliation no possible, surgical correction not possible

Palliative surgery for bowel Palliative surgery for bowel obstruction in recurrent ovarian obstruction in recurrent ovarian cancercancer

Results and Conclusions: If surgery resulted in successful palliation,

median survival 11.6 months vs 3.9 months for all other patients ( P < 0.01).

The extension of survival compared with prior studies may be attributable to improved patient selection for surgery and perhaps the ability to tolerate chemotherapy after surgery.

Conclusions ( I )

MBO is a complex problem in patients with ovarian cancer, but it is a severe complication affecting survival and, moreover, quality of life (QoL).

The exact incidence is unknown and retrospective review show 20-50% of patients with ovarian cancer present with symptoms of MBO.

The etiology of MBO is varied, including progressive intra-abdominal tumor growth, intra-luminal occlusion, intestinal motility problem, and result of prior therapy.

The treatment of MBO, surgical or medical, is not decided based on a fixed protocol, but the choice of therapy is individualized.

Conclusions ( II )

The goal of treatment of MBO are palliative rather than curative measures, improving the QoL with a limited life expectance, and the decision to attempt surgery is extremely difficulty that is one of the most challenging clinical scenarios.

When such a decision is under consideration, one must taking into account of the change of successful palliation, risk of repeat obstruction, QoL for patient after the surgery, ability to administer further chemotherapy, as well as the rates of operative morbidity and mortality.

If the surgery resulted in successful palliation, median survival was longer than all other patients with MBO.

Thank you for your attention !!