Predicting risk of_malignancy_in_adnexal_masses.4


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Predicting risk of_malignancy_in_adnexal_masses.4

  1. 1. Original ResearchPredicting Risk of Malignancy in AdnexalMassesJohn M. McDonald, MD, Stacey Doran, BS, Christopher P. DeSimone, MD, Fred R. Ueland, MD,Paul D. DePriest, MD, Rachel A. Ware, MD, Brook A. Saunders, MD, Edward J. Pavlik, PhD,Scott Goodrich, MD, Richard J. Kryscio, PhD, and John R. van Nagell Jr, MDOBJECTIVE: To estimate the accuracy of preoperative cancer and 98.6% of patients with stage III and stage IVultrasonography, serum CA 125, and patient demograph- ovarian cancer.ics as a means of predicting risk of malignancy in women CONCLUSION: Patients with solid or complex ovarianwith a ultrasonographically confirmed adnexal mass. tumors and an elevated serum CA 125 level (greater thanMETHODS: Tumor morphology derived from ultrasono- 35 units/mL) are at high risk of ovarian malignancy.graphic images, tumor size, tumor bilaterality, serum CA (Obstet Gynecol 2010;115:687–94)125, and patient demographics were evaluated preoper- LEVEL OF EVIDENCE: IIatively in 395 patients undergoing surgery from 2001 to2008. Tumor morphology was classified as complex,solid, or cystic. Preoperative findings were comparedwith tumor histologic findings at the time of surgery.Multivariable classification and regression tree analysis O varian cancer remains the leading cause of death from gynecologic cancers in the United States. It was estimated that in 2009 there would bewere used to identify a group of patients at high risk of 21,554 new cases of ovarian cancer, and that 14,600ovarian malignancy. women would die as a result of disease.1 Case– controlRESULTS: One hundred eighteen patients had ovarian studies have indicated that women with ovarian can-cancer, 13 patients had ovarian tumors of borderline cer commonly experience a pattern of symptoms thatmalignancy, and 264 had benign ovarian tumors. Multi- include bloating, pelvic/abdominal pain, difficultyvariable classification and regression tree analysis defined eating/feeling full quickly, and urinary urgency orwomen at high risk of ovarian malignancy as those with frequency.2,3 These symptoms were found to be morean adnexal mass having complex or solid morphologyand a serum CA 125 value greater than 35 units/mL. This commonly associated with ovarian cancer, when theydefinition had a positive predictive value of 84.7% and a were newly experienced, and occurred more that 12negative predictive value of 92.4% and correctly identi- times per month.4 Recently, consensus groups havefied 77.3% of patients with stage I and stage II ovarian recommended that women who experience symp- toms suggestive of ovarian cancer should undergo a See related editorial on page 680. complete physical examination, and in certain cases, transvaginal ultrasonography and CA 125 testing.From the Division of Gynecologic Oncology, Department of Obstetrics and Although the majority of patients with these symp-Gynecology, and Departments of Statistics and Biostatistics, University of toms will not have ovarian cancer, those who do willKentucky Chandler Medical Center–Markey Cancer Center, Lexington,Kentucky. require complete surgical staging and aggressive tu-Supported by research grants from the Kentucky Department of Health and mor debulking to maximize their chances of surviv-Human Services and the Telford Foundation. al.5–7 In this regard, it is important to establish riskCorresponding author: John Rensselaer van Nagell Jr, MD, Division of profiles of patients with ultrasonographically con-Gynecologic Oncology, Department of Obstetrics and Gynecology, University firmed adnexal tumors so that they can receive ap-of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536; e-mail: propriate treatment and, when necessary, referral specialty cancer care. The authors postulate that theFinancial DisclosureThe authors did not report any potential conflicts of interest. addition of ultrasonographically generated tumor morphology to patient demographics and serum bi-© 2010 by The American College of Obstetricians and Gynecologists. Publishedby Lippincott Williams & Wilkins. omarker profiles could improve prediction of malig-ISSN: 0029-7844/10 nancy in a clinically detectable adnexal mass. ThisVOL. 115, NO. 4, APRIL 2010 OBSTETRICS & GYNECOLOGY 687
  2. 2. investigation was undertaken to estimate the accuracy tional Federation of Gynecology and Obstetrics sys-of a combination of patient demographics, ultrasono- tem. Data were entered into a MEDLOG databasegraphically generated tumor morphology, and serum (MEDLOG Systems, Crystal Bay, NV) and exportedCA 125 values in predicting risk of malignancy in into an Excel (Microsoft Corp., Redmond, WA)adnexal masses. spreadsheet for analysis using WinSTAT (R. Fitch Software, Bad Krozingen, Germany), SPSS (SPSS,MATERIALS AND METHODS Inc., Chicago, IL), and PC-SAS with the EnterpriseThis investigation was undertaken after approval Miner statistical software (SAS Institute, Inc., Cary, NC).from the University of Kentucky Human Subjects Proportions were compared using ␹2 statistics orInstitutional Review Board. Study participants were Fisher exact tests. Means were compared using two-women referred to the University of Kentucky–Mar- sample t tests. Statistical significance was determinedkey Women’s Cancer Center with a diagnosis of an at the .05 level. Multivariable analyses used theadnexal mass on pelvic examination who underwent classification and regression tree procedure, a non-surgery at this institution from 2001 to 2008. parametric method that defines or accepts cut points The following demographic data were obtained and uses training and validation sets to optimize rulesfor all study patients: age, height, weight, gravidity, for the analysis.9 The training set is formed by split-family history of breast or ovarian cancer, personal ting the entire sample in half after stratification forhistory of cancer, and menopausal status. Postmeno- malignant cases and benign controls.pausal was defined as the absence of menses for aminimum of 12 months. Family history was consid- RESULTSered positive if the patient had a first-degree relative Between July 2001 and December 2008, 399 patients(ie, mother, sister, or daughter) or a second-degree referred to the outpatient clinic of the University ofrelative (ie, grandmother, granddaughter, aunt, or Kentucky–Markey Women’s Cancer Center for eval-niece) with documented ovarian or breast cancer. All uation of an adnexal mass on pelvic examinationwomen underwent pelvic examination, transvaginalultrasonography, and serum CA 125 determinationwithin 2 weeks before surgery. Transvaginal ultra- Table 1. Patient Demographics, Tumor Variables,sonography was performed using General Electric and Biomarker Profiles in Patients(Milwaukee, WI) Logic 400 or Voluson ProV ultra- Studied (N‫)593؍‬sound units with a 5-mHz vaginal probe as described Mean Rangepreviously.8 Tumor dimensions from ultrasono-graphic images were recorded, and tumor morphol- Age (y) 51.6 (Ϯ0.8) 10–86ogy was classified as cystic, solid, or complex (con- Height (in) 64 (Ϯ0.02) 55–72 Weight (lb) 173 (Ϯ2.8) 78–384taining both solid and cystic components). All Gravidity 2.4 (Ϯ0.1) 0–21ultrasonograms were reviewed by at least one of the Family historyauthors. All tumors classified as cystic were unilocu- Ovarian cancer 48 (12)lar, whereas cystic tumors with septations were in- Breast cancer 64 (16)cluded in the complex group. Ascites was defined as Menopausal status Premenopausal 176 (45)free fluid more than 60 mL in the abdomen/pelvis Postmenopausal 219 (55)confirmed by ultrasonography. Serum CA 125 deter- Tumor morphologyminations were performed using a two-site sandwich Cystic 123 (31)paramagnetic particle chemiluminescent immunoen- Complex 236 (60)zymatic assay with a normal value less than 35 Solid 36 (9) Tumor diameterunits/mL. Serum samples with values exceeding 10 cm or less 291 (74)5,000 units/mL were diluted to end point for a final More than 10 cm 104 (26)result. Ascites After surgical removal, the dimensions of each Present 54 (14)tumor were recorded, and frozen section histologic Absent 341 (86) CA 125 (units/mL)evaluation was performed. Tumors were classified Less than 35 247 (62)histologically according to the World Health Organi- 35–59 38 (10)zation system. Patients with a histologic diagnosis of 60–120 23 (6)ovarian malignancy underwent immediate tumor de- More than 120 87 (22)bulking and surgical staging according to the Interna- Data are mean (Ϯstandard deviation) or n (%).688 McDonald et al Risk of Malignancy in an Adnexal Mass OBSTETRICS & GYNECOLOGY
  3. 3. were included in this investigation. Four patients had followed by serous cystadenocarcinoma, mucinoustheir first CA 125 determination after surgery and cystadenocarcinoma, and clear-cell carcinoma.were excluded from further evaluation. Demographic The relationship of demographic, biomarker, anddata, biomarker profiles, and tumor characteristics of tumor variables to risk of malignancy in patients withthe patients evaluated are listed in Table 1. Fifty-five an adnexal mass is presented in Table 2. Variablespercent of patients were postmenopausal and 40% statistically related to risk of malignancy were tumorwere aged 55 years or older. Sixty-four patients (16%) morphology, ascites, serum CA 125 level, tumor size,had a family history of breast cancer, 48 patients tumor bilaterality, menopausal status, and age.(12%) had a family history of ovarian cancer, and one Tumor morphology from ultrasonographicallypatient was BRCA1 positive. Two hundred thirty-six generated images was related directly to risk of ma-masses (60%) were ultrasonographically complex lignancy. There were 236 complex adnexal masses,(Fig. 1A), 123 (31%) were cystic (Fig. 1B), and 36 (9%) and 120 (51%) were malignant. None of the fivewere solid (Fig. 1C). Five of the 236 complex adnexal complex masses with septal morphology without solidmasses (2.1%) were cystic ovarian tumors with thick areas were malignant. There were 36 solid adnexalsepta but no solid areas. Radiologic evidence of masses, and 11 (32%) were malignant. In contrast,ascites was present in 54 patients (14%). Serum CA there were 123 cystic adnexal masses, and none were125 level was elevated (more than 35 units/mL) in ovarian tumors of borderline malignancy or invasive148 patients (38%) and was more than 120 units/mL ovarian cancers (PϽ.001). The finding of purely cysticin 87 patients (22%). morphology in an adnexal mass was associated with a At the time of surgery, 264 patients (67%) were negative predictive value (NPV) for malignancy of 100%.found to have benign ovarian tumors, 118 patients Fifty-four patients with an adnexal mass had(30%) had ovarian cancer, and 13 patients (3%) had radiologically confirmed ascites, and all of these pa-ovarian tumors of borderline malignancy. The stage tients had invasive epithelial ovarian cancer (stage IC,distribution of the patients with ovarian tumors of nϭ2; stage IIC, nϭ1; stage IIIC, nϭ49; and stage IV,borderline malignancy and ovarian cancer was as nϭ2). Therefore, the finding of documented ascitesfollows: stage I, nϭ38; stage II, nϭ17; stage III, in a patient with a complex or solid adnexal massnϭ74; and stage IV, nϭ2. The most common cell had a positive predictive value (PPV) for malig-types of ovarian malignancy were adenocarcinoma, nancy of 100%. Fig. 1. Patterns of adnexal mor- phology. A. Complex adnexal mass, 12 cm in diameter; the cys- tic periphery is marked with clear arrows and the internal solid component is marked with solid arrows (histology: clear-cell carci- noma). B. Cystic adnexal mass, 9.4 cm in diameter, periphery is marked with clear arrows (histol- ogy: ovarian serous cystade- noma). C. Solid adnexal mass, 5 cm in diameter; the periphery is marked with clear arrows (histol- ogy: ovarian adenocarcinoma). McDonald. Risk of Malignancy in an Adnexal Mass. Obstet Gynecol 2010.VOL. 115, NO. 4, APRIL 2010 McDonald et al Risk of Malignancy in an Adnexal Mass 689
  4. 4. Table 2. Demographic, Tumor, and Biomarker patients with complex and solid adnexal masses are Variables Related to Risk of Malignancy listed in Table 3. The only benign histologic finding (N‫)593؍‬ consistently associated with an elevated serum CAVariable Total Malignant P 125 value was ovarian endometriosis. Thirteen (48%) of 27 women with an ovarian endometrioma had anAge (y) elevated serum CA 125 value (more than 35 units/ 55 or younger 239 58 (24.3) Ͻ.001 Older than 55 156 73 (46.8) mL), and 5 (18%) had a serum CA 125 value moreGravidity than 60 units/mL. There were 114 women with other 1 or less 125 41 (32.8) .92 benign complex or solid adnexal masses, and only 1 More than 1 270 90 (33.3) patient (with an ovarian fibroma) had a CA 125 levelMenopausal status more than 60 units/mL. As expected, serum CA 125 Premenopausal 176 43 (24.4) Ͻ.001 Postmenopausal 219 88 (40.2) values were related directly to stage of disease inWeight (lb) patients with ovarian malignancies. Serum CA 125 200 or less 314 116 (36.9) Ͻ.02 values were elevated (more than 35 units/mL) in More than 200 81 15 (18.5) 30.7% of patients with an ovarian tumor of borderlineFamily history of ovarian malignancy, 77.2% of patients with stage I and stage II cancer Yes 48 16 (33.3) .98 ovarian cancer, and 98.6% of patients with stage IIIC No 347 115 (33.1) and IV ovarian cancer. All 54 patients with ascitesFamily history of breast had an elevated (more than 35 units/mL) serum CA cancer 125 level, and 52 (96.2%) had a CA 125 level more Yes 64 20 (31.3) .72 than 60 units/mL. No 331 111 (33.5)Tumor morphology Risk of malignancy in an adnexal mass was signif- Cystic 123 0 (0) Ͻ.001* icantly higher in women older than 55 years than in Complex 236 120 (50.8) younger women (PϽ.001), in postmenopausal women Solid 36 11 (30.6) compared with premenopausal women (PϽ.001), inAscites women with bilateral compared with unilateral ovarian Negative 341 77 (22.6) Ͻ.001 Positive 54 54 (100) tumors (PϽ.01), and in women whose adnexal massesTumor laterality were more than 10 cm in diameter compared with Unilateral 375 119 (22.6) Ͻ.01 smaller tumors (PϽ.001). A family history of ovarian Bilateral 20 12 (60) cancer or breast cancer in a woman with an adnexalTumor diameter mass was not associated statistically with an increased 10 cm or less 291 67 (23) Ͻ.001 More than 10 cm 104 64 (61.5) risk of malignancy in the population studied.CA 125 (units/mL) Although many variables were correlated with ma- Ͻ.001 lignancy, only a small number had acceptable positive † Less than 35 247 19 (7.7) 35–59 38 13 (34.2) or NPVs (Table 4). Classification and regression tree 60–120 23 17 (73.9) multivariable analysis considered age, gravidity, post- More than 120 87 82 (94.2) menopausal status, weight, family history of ovarianData are n or n (%). cancer or breast cancer, tumor morphology, ascites,* Cystic compared with complex or solid tumor morphology.† CA 125 less than 35 units/mL compared with 35–59, 60 –120, tumor bilaterality, maximum tumor diameter, and CA or more than 120 units/mL. 125 value. This analysis found the most accurate signif- icance of interactions to declare a high risk of malig- nancy if a patient had an adnexal mass with complex or Serum CA 125 values were related directly to risk solid morphology and a serum CA 125 value more thanof malignancy in women with an adnexal mass. Only 35 units/mL. The statistics for the training and validation19 (7.7%) of 247 patients with a normal serum CA 125 sets indicated uniformly high performances for sensitiv-value (less than 35 units/mL) had ovarian cancer. ity, specificity, and predictive values across both theConversely, 13 of 83 patients (34.2%) with a serum training and validation sets.CA 125 value of 35–59 units/mL, 17 of 23 patients Statistical parameters associated with the high-risk(73.9%) with a serum CA 125 value of 60 –120 definition are listed in Table 5. Using the stated high-riskunits/mL, and 82 of 87 patients (86.8%) with a CA 125 parameters resulted in a sensitivity of 30.8% for ovarianvalue more than 120 units/mL had borderline or tumors of borderline malignancy, 77.3% for earlymalignant ovarian tumors (PϽ.001). Serum CA 125 stage (I and II) ovarian cancer, and 98.6% for ad-values related to specific histologic diagnoses in all vanced stage (III and IV) ovarian cancer. Increasing690 McDonald et al Risk of Malignancy in an Adnexal Mass OBSTETRICS & GYNECOLOGY
  5. 5. Table 3. CA 125 Related to Histology in Ultrasonographically Complex or Solid Adnexal Tumors (n‫)272؍‬ CA 125 Less Than 35–59 60–120 More ThanHistology n 35 Units/mL Units/mL Units/mL 120 Units/mLFibroma 15 12 2 1 0Cystadenofibroma 27 25 2 0 0Endometrioma 27 14 8 1 4Serous cystadenoma 22 22 0 0 0Cystic teratoma 20 20 0 0 0Mucinous cystadenoma 15 15 0 0 0Granulosa cell tumor 4 3 1 0 0Pedunculated myoma 7 6 1 0 0Sertoli-Leydig cell tumor 1 0 1 0 0Brenner tumor 3 3 0 0 0Mucinous LMP 5 3 1 0 1Serous LMP 8 5 1 1 0Clear-cell carcinoma 8 3 2 3 0Carcinosarcoma 4 0 0 0 4Mucinous cystadenocarcinoma 5 2 0 1 1Serous cystadenocarcinoma 8 1 0 0 7Adenocarcinoma 93 5 8 12 68LMP, low malignant potential.Data are n.the cutoff value of CA 125 from 35 units/mL to 60 tumor morphology obtained from ultrasonographicunits/mL and keeping the other parts of the definition images, and serum CA 125 levels is useful in estimat-the same increased specificity from 92.4% to 96.6% ing the risk of malignancy in women with an adnexalbut lowered sensitivity from 84.7% to 80.9% and mass. For example, the risk of neoplasia in unilocularmissed 13 patients with stage I or stage II ovarian cystic ovarian tumors is very low. This morphologiccancer. Therefore, a cutoff value of 35 units/mL for pattern was present in 123 (31%) of 395 adnexalCA 125 was used in the final high-risk definition. This tumors, and no patient had either a borderline or andefinition correctly identified 34 of 44 patients with invasive ovarian malignancy. This confirms the ob-stage I and stage II ovarian cancer and 93 of 94 servation by Roman and colleagues10 who, in a sum-patients with stage III and stage IV ovarian cancer. mary of the literature, reported a 0.7% rate of malig-Also, it correctly excluded 244 of the 264 patients nancy in 569 unilocular cystic ovarian tumors 10 cmwith benign ovarian tumors. or less in diameter. Similarly, Modesitt and col- leagues11 followed more than 3,200 women withDISCUSSION unilocular cystic ovarian tumors less than 10 cm inThe observation that the occurrence of certain symp- diameter for an average of 6 years without operativetoms may precede the clinical diagnosis of ovarian intervention. No patient developed ovarian cancer,cancer has resulted in the recommendation that and 69% of these tumors resolved spontaneously overwomen experiencing the recent onset of bloating, the period of observation. There is no doubt thatpelvic/abdominal pain, feeling full quickly after eat- some unilocular cystic ovarian tumors grow to signif-ing, or urinary urgency/frequency should consult a icant size and require surgical removal. However, thephysician and undergo a complete physical examina- risk of malignancy even in larger cystic lesions is low,tion. Women having a clinically palpable abnormality particularly in women with a normal CA 125 level. Inin the pelvis or those with persisting symptoms in the the present study, there were 27 unilocular cysticpresence of a normal pelvic examination are advised ovarian tumors more than 10 cm diameter, and allto undergo transvaginal ultrasonography and CA 125 were benign.testing. In contrast, adnexal masses with complex or solid The findings of this investigation indicate that morphology are associated with a significant risk ofanalysis of data concerning patient demographics, malignancy. There were 272 patients with a complexVOL. 115, NO. 4, APRIL 2010 McDonald et al Risk of Malignancy in an Adnexal Mass 691
  6. 6. Table 4. Sensitivity, Specificity, Positive and Negative Predictive Values, and 95% Confidence Limits of Each Variable Identifying or Ruling Out Ovarian Malignancy Sensitivity Specificity (95% CL) (95% CL)Variable Sensitivity Lower Upper Specificity Lower UpperAge older than 55 y 55.7 47.2 64.2 68.6 63.0 74.2Gravidity more than 1 68.7 60.8 76.6 31.8 26.2 37.4Postmenopausal 67.2 59.1 75.2 50.4 44.3 56.4Weight more than 200 lb 11.5 6.0 16.9 75.0 69.8 80.2Family history Ovarian cancer 12.2 6.6 17.8 87.9 83.9 91.8 Breast cancer 15.3 9.1 21.4 83.3 78.8 87.8Tumor morphology Cystic 100.0 97.7 100.0 46.6 40.6 52.6 Complex 91.6 86.9 96.4 56.1 50.1 62.0Ascites 41.2 32.8 49.7 100.0 98.9 100.0Tumor bilaterality 9.2 4.2 14.1 97.0 94.9 99.0Tumor diameter More than 10 cm 48.9 40.3 57.4 84.8 80.5 89.2CA 125 level more than 35 units/mL 85.5 79.5 91.5 86.4 82.2 90.5CL, confidence limit; PPV, positive predictive value; NPV, negative predictive value.or solid adnexal mass, and 131 (48%) had an ovarian tricians and Gynecologists and the Society of Gyne-malignancy. These women form the basis of a high- cologic Oncologists.13 This report stated that 69.8% ofrisk group for ovarian cancer. In the present investi- postmenopausal women with an adnexal mass and agation, documented ascites in a woman with a com- serum CA 125 value more than 35 units/mL had anplex or solid adnexal mass was uniformly predictive ovarian malignancy and that an elevated serum CAof ovarian cancer. There were 54 patients with this 125 value in a patient with a clinically detectablefinding, and all had epithelial ovarian cancer. These pelvic mass could be used as one indication forresults are consistent with the findings of Im and patient referral for subspecialty care. In the presentcolleagues12 who, in a multiinstitutional review, re- investigation, more than three fourths of women withported that 79% of postmenopausal women with a a complex or solid adnexal mass and a CA 125 valueclinically detectable pelvic mass and ascites had an more than 35 units/mL had either borderline orovarian malignancy. invasive ovarian cancer. The use of serum CA 125 as a method of When evaluating a number of variables, includ-predicting risk of malignancy in patients with a clin- ing patient demographics, tumor morphology, andically detectable pelvic mass was suggested in 2002 by CA 125 levels, as predictors of malignancy, multiva-a joint publication of the American College of Obste- riable classification and regression tree analysis de-Table 5. Statistical Parameters Associated with a High-Risk* Group for Ovarian Cancer as Defined by Multivariable Classification and Regression Tree AnalysisCriteria TP FP TN FN PPV NPV Sensitivity† Specificity‡Total malignancies (nϭ131) 111 20 244 20 0.847 0.924 0.847§ 0.924§Borderline malignancy (nϭ13) 4 20 244 9 0.167 0.964 0.308 0.924Stages I and II ovarian 34 20 244 10 0.630 0.961 0.773 0.924 malignancy (nϭ44)Stages III and IV ovarian 73 20 244 1 0.785 0.996 0.986 0.924 malignancy (nϭ74)TP, true positive; FP, false positive; TN, true negative; FN, false negative; PPV, positive predictive value (TP/TPϩFP); NPV, negative predictive value (TN/TNϩFN).* High-risk defined as a complex or solid adnexal mass with a CA 125 value more than 35 units/mL.† Sensitivity, (TP/TPϩFN).‡ Specificity, (TN/TNϩFN).§ These figures vary within 1 standard error (Ϯ3.1% for sensitivity and Ϯ1.6% for specificity) when the sample is randomly split into training and validation sets.692 McDonald et al Risk of Malignancy in an Adnexal Mass OBSTETRICS & GYNECOLOGY
  7. 7. PPV PPV (95% CL) (95% CL)PPV Lower Upper NPV Lower Upper 46.8 39.0 54.6 75.7 70.3 81.2 33.3 27.7 39.0 67.2 59.0 75.4 40.2 33.7 46.7 75.6 69.2 81.9 18.5 10.1 27.0 63.1 57.7 68.4 33.3 20.0 46.7 66.9 61.9 71.8 31.3 19.9 42.6 66.5 61.4 71.6 48.2 42.2 54.1 100.0 97.6 100.0 50.8 44.5 57.2 93.1 89.1 97.0100.0 94.4 100.0 77.4 73.0 81.9 60.0 38.5 81.5 68.3 63.6 73.0 61.5 52.2 70.9 77.0 72.1 81.8 75.7 68.8 82.6 92.3 89.0 95.6fined high risk as women with a complex or solid netic testing,17 and this information should be taken intoadnexal mass and a serum CA 125 value of more than consideration in determining optimal treatment for a35 units/mL. In the population studied, this definition patient with an adnexal mass.of high risk was associated with a PPV of 84.7% and As an increasing number of women who havea NPV of 92.4% and correctly identified 34 (77.3%) of symptoms suggestive of ovarian cancer are evaluated,44 patients with stage I or stage II ovarian cancer as clinicians will be asked to determine which patientswell as 73 of 74 patients (98.6%) with stage III or stage are at significant risk for ovarian cancer. Data fromIV ovarian cancer. Thus, including tumor morphol- the present investigation suggest that the combinationogy significantly increases predictive values beyond of ultrasonographic tumor morphology and serumthe PPV of 24.3% for stage I or II ovarian cancer and CA 125 value improves the discrimination of women56.8% for stage III or IV ovarian cancer associated at risk of ovarian cancer from those with benignwith the original American College of Obstetricians adnexal lesions. These findings should be helpful inand Gynecologists/Society of Gynecologic Oncolo- determining which patients can be followed withoutgists high-risk criteria.14 In the present study, raising surgery, which patients are likely to have a benignthe cutoff value of CA 125 from 35 units/mL to 60 ovarian tumor, and which patients are at high risk ofunits/mL in the definition of high risk would have ovarian malignancy and should be referred for sub-increased specificity for identifying ovarian cancer specialty care.cases but would have lowered sensitivity and resultedin missing a significant number of patients with REFERENCESearly-stage disease. This is important because several 1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun M. Cancerstudies have reported as high as a 24% survival statistics 2009. CA Cancer J Clin 2009;59:225– 49.advantage for patients with early-stage ovarian cancer 2. Goff BA, Mandel LS, Melancon CH, Muntz HG. Frequency ofwho received comprehensive surgical staging and symptoms of ovarian cancer in women presenting to primary care clinics. JAMA 2004;291:2705–12.treatment by a gynecologic oncologist.15,16 3. Smith LH, Morris CR, Yasmeen S, Parikh-Patel A, Cress RD, Although family history of ovarian cancer or breast Romano PS. Ovarian cancer: can we make the clinical diag-cancer was not statistically associated with an increased nosis earlier? Cancer 2005;104:1398 – 407.risk of ovarian cancer in this investigation, a hereditary 4. Goff BA, Mandel L, Drescher CW, Urban N, Gough S,cancer risk assessment was not routinely performed on Schurman KM, et al. Development of an ovarian cancerevery patient enrolled in this study. Clearly, women symptom index. Cancer 2007;109:221–7.with a strong family history of ovarian or breast cancer 5. Bristow RE, Tomacruz RS, Armstrong DK, Trimble EL, Montz FJ. Survival effect of maximal cytoreductive surgery foror women who are members of populations with a high advanced ovarian carcinoma during the platinum era: a meta-prevalence of “founder mutations” should undergo ge- analysis. J Clin Oncol 2002;20:1248 –59.VOL. 115, NO. 4, APRIL 2010 McDonald et al Risk of Malignancy in an Adnexal Mass 693
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