ORIGINAL STUDY
The Value of Random Biopsies, Omentectomy, and Hysterectomy in Operations for Borderline Ovarian Tumors Gitte Schultz Kristensen, MD,* Doris Schledermann, MD,Þ Ole Mogensen, Prof, DMSci,þ and Kirsten Marie Jochumsen, MD, PhDþ
Objective: Borderline ovarian tumors (BOTs) are treated surgically like malignant ovarian tumors with hysterectomy, salpingectomy, omentectomy, and multiple random peritoneal biopsies in addition to removal of the ovaries. It is, however, unknown how often removal of macroscopically normal-appearing tissues leads to the finding of microscopic disease. To evaluate the value of random biopsies, omentectomy, and hysterectomy in operations for BOT, the macroscopic and microscopic findings in a cohort of these patients were reviewed retrospectively. Materials: Women treated for BOT at Odense University Hospital from 2007 to 2011 were eligible for this study. Data were extracted from electronic records. Intraoperative assessment of tumor spread (macroscopic disease) and the microscopic evaluation of removed tissues were the main outcome measures. Results: The study included 75 patients, 59 (78.7%) in International Federation of Gynecology and Obstetrics stage I, 9 (12%) in stage II, and 7 (9.3%) in stage III. The histologic subtypes were serous (68%), mucinous (30.7%), and Brenner type (1.3%). Macroscopically radical surgery was performed in 62 patients (82.7%), and 46 (61.3%) received complete staging. The surgeon’s identification of macroscopic tumor spread to the contralateral ovary and the peritoneum had a sensitivity of 88% and 69.2% and a specificity of 90.2% and 92.5%, respectively. The macroscopic assessment of the uterine surface, the omentum, and the pelvic and para-aortal lymph nodes was not a good predictor of microscopic disease. During follow-up, 4 patients (5.3%) relapsed with no relation to surgical radicality or the extent of staging procedures. Conclusions: Ovaries and peritoneal surfaces with a macroscopically normal appearance rarely contain a microscopic focus of BOT. Key Words: Borderline ovarian tumors, Macroscopic evaluation, Microscopic evaluation, Complete staging, Radical surgery Received November 21, 2013, and in revised form February 12, 2014. Accepted for publication March 6, 2014. (Int J Gynecol Cancer 2014;24: 874Y879)
*Emergency Department, Kolding Hospital, Kolding, Denmark; and Departments of †Pathology, and ‡Obstetrics and Gynecology, Odense University Hospital, Odense, Denmark. Address correspondence and reprint requests to Gitte Schultz Kristensen, MD, Department of Obstetrics and Gynecology, Odense University Hospital, Sdr. Boulevard 29, DK-5000 Odense C, Denmark. E-mail: [email protected]. The authors declare no conflicts of interest. Copyright * 2014 by IGCS and ESGO ISSN: 1048-891X DOI: 10.1097/IGC.0000000000000140
874
when the World Health Organization first classiI nfied1973, borderline ovarian tumors (BOTs) as a separate type
of ovarian tumor, the management of BOT was equal to that of ovarian carcinomas. Since then, a number of authors have shown that adjuvant chemotherapy and irradiation are not beneficial for women with BOT.1 Similarly, removal of pelvic and para-aortic lymph nodes has been shown not to improve long-term survival or recurrence.2,3 Recognizing that there are ovarian epithelial neoplasms that both morphologically and in natural history seem to fall
International Journal of Gynecological Cancer
& Volume 24, Number 5, June 2014
Copyright © 2014 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
International Journal of Gynecological Cancer
& Volume 24, Number 5, June 2014
between usual carcinoma and completely benign neoplasms, the term BOT was proposed. The 2 most common morphological types are serous and mucinous BOT. Grossly, most BOTs are cystic and solid with friable papillary nodules that may project into otherwise smooth-walled cysts or from the surface of the ovary. The borderline areas may make up a small percentage of the neoplasm (by definition, 910%) or may be more extensively present.4 Microscopically, most BOTs are characterized by papillary proliferations of epithelial cells exhibiting mild or at the most moderate nuclear atypia. By definition, stromal invasion is absent in BOT. Extraovarian disease in association with a serous BOT is referred to as implants and is found more frequently with tumors that have an exophytic component on the ovarian surface. Most commonly, implants are located in the omentum and on peritoneal surfaces but may also be located in regional lymph nodes. Implants are categorized as either noninvasive or invasive. Invasive implants show obvious destructive invasion recognized by irregular infiltration into underlying tissue. Separation of the implants into invasive and noninvasive subtypes carries prognostic implications because the rare fatal cases of BOT most often are those with invasive implants. In the recent years, young women with disease confined to 1 ovary have been treated more conservatively to preserve their fertility. Conservative treatment increases the risk for recurrence but has not been shown to reduce longterm survival.5,6 The International Federation of Gynecology and Obstetrics (FIGO) guidelines and the current Danish guidelines for treatment of BOT recommend surgical removal of the ovaries, the uterus, and the omentum; multiple peritoneal biopsies; and cytologic examination of peritoneal fluids. In case of a mucinous BOT, removal of the appendix is also recommended.7,8 In the latest annual report from the Danish Gynecologic Cancer Group, the overall 5-year survival after treatment of BOT in Denmark (all stages) is calculated to be 92%.9 Removal of tissues with a focus of BOTwill most likely lower the risk for recurrence, but it is unknown how often removal of a healthy-looking tissue will lead to the finding of a microscopic focus of BOT. The aim of this retrospective study was to evaluate how often microscopic disease is found in healthy-looking tissues in operations for BOT and concurrently review the need for removal of these normallooking tissues.
MATERIALS AND METHODS All women diagnosed with BOT (International Classification of Diseases, Tenth Revision, code D391A) at Odense University Hospital between January 1, 2007, and December 31, 2011, were identified through a search in the hospital’s electronic database. Patients diagnosed with BOT before 2007 who relapsed in 2007 to 2011 were not included. A total of 75 patients were eligible for this study. Patients were followed from the initial BOT diagnosis to October 2, 2012. All medical records were found in the electronic health record systems. The records were reviewed to collect data regarding age, tumor size, surgical management, and postoperative
Surgery for Borderline Ovarian Tumors
management. Macroscopic findings at primary surgery and in staging operations were recorded. Special interest was paid to the macroscopic assessment of the ovaries, the uterine serosa, the omentum, the peritoneal surfaces, the appendix, and the lymph nodes during surgery, and this was compared with the microscopic evaluation of these tissues at histologic examination. The patients were primarily staged on the basis of intraoperative findings, and their final stage was based on the surgical findings combined with the results of the histologic and cytologic examination according to the FIGO classification. Radical surgery was defined as removal of the uterus and both ovaries combined with complete staging. Complete staging procedures were defined according to the FIGO guidelines as radical surgery combined with cytologic examination of peritoneal fluids, multiple peritoneal biopsies, and omentectomy (with modification because lymph node sampling is still part of the complete staging procedures in the FIGO guidelines).7 In case of a mucinous tumor, appendectomy was also part of the complete staging procedure. Incomplete staging was defined as the lack of 1 or more of the abovementioned procedures. Lymph node sampling was not a part of the staging procedure but was performed occasionally if there was clinical or radiologic suggestion of involvement. A database was created in Epidata version 1.1.2. All statistical analyses were carried out in Stata version 12.1. Two categorical, binary variables were compared using the Fisher exact test, for example, when comparing the macroscopic and microscopic evaluation of the uterus. The W2 test was used when comparing 2 categorical variables with 2 or more categories, for example, comparing the histologic subtype with recurrence. From these tests, P values were calculated. Generally, a P value of less than 0.05 was considered to be statistically significant. The concordance between macroscopic and microscopic findings was evaluated using J statistics. The surgeon’s ability to identify tumor spread during surgery was evaluated, calculating the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The incidence of recurrence and malignant transformation was calculated. This study was approved by the Danish Health and Medicines Authority, case number 3-3013-312/1/. This study was also approved by the Danish Data Protection Agency, case number 13/7525.
RESULTS Characteristics of the 75 patients with BOTs are shown in Table 1. The results from the macroscopic and microscopic evaluation of the tissues and the concordance between the results are listed in Table 2. Table 2 does not contain data for all of the 6 types of tissues from all 75 patients. The reason for this is that the organ/tissue had already been removed (for example, the uterus or the appendix), the description of the tissue in the surgical record was insufficient, or the tissues had not been removed during surgery (for example, the appendix or the lymph nodes). Complete staging procedures were carried out in 46 women (61.3%) either at primary surgery or at a later staging operation after BOT had been diagnosed. In 29 women
* 2014 IGCS and ESGO
Copyright © 2014 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
875
International Journal of Gynecological Cancer
Kristensen et al
TABLE 1. Characteristics of the 75 patients with BOT Patient Characteristics Age, median (range), y 54 (25Y90) Histologic subtypes Serous 51 (68%) Mucinous 23 (30.7%) Brenner type 1 (1.3%) FIGO stage Stage Ia 40 (50.3%) Stage Ib 2 (2.7%) Stage Ic 17 (22.7%) Stage IIa 0 Stage IIb 7 (9.3%) Stage IIc 2 (2.7%) Stage IIIa 5 (6.7%) Stage IIIb 2 (2.7%) Stage IIIc 0 Stage IV 0 Surgery Primary 55 (73.3%) Staging surgery 19 (25.3%) Radical surgery after former 1 (1.3%) conservative surgery Radical surgery 62 (82.7%) Radical surgery, median age (range) 55 (33Y86) Conservative surgery, median age (range) 40 (25Y90) Complete staging 46 (61.3%) Tumor size, mean (range), cm 12.52 (0.6Y30) Other histologic findings Noninvasive implants 14 (18.7%) Invasive implants 2 (2.7%) Stromal microinvasion 3 (4%) Recurrence 4 (5.3%) Follow-up time, median (range), mo 28.7 (3.8Y67.1) Recurrence time, median (range), mo 22.5 (7.4Y42.3)
(38.7%), 1 or more of the staging procedures (most often concerning peritoneal sampling or the cytologic examination of peritoneal fluids) were omitted. The patients were staged before and after the results of the histologic and cytologic examination. The histologic and cytologic examinations led to upstaging in 14 cases (18.7%) and downstaging in 4 cases (5.3%). Upstaging was caused by the following: & The finding of noninvasive implants in the visceral peritoneum (not covering the internal female genitals): 5 presumed stage I tumors were upstaged to stage IIb. & The finding of noninvasive implants in the omentum: 3 presumed stage I tumors and 1 stage II tumor were upstaged to stage IIIa.
876
& Volume 24, Number 5, June 2014
& Ovarian surface growth: 2 presumed stage Ia tumors and 1 stage Ib tumor were upstaged to stage Ic. & Positive cytologic findings: 1 tumor was upstaged from stage Ib to Ic and 1 tumor was upstaged from stage IIb to IIc. Downstaging was caused by the following: & Bilateral ovarian tumors were suspected but not confirmed by histology: 2 presumed stage Ib tumors were downstaged to stage Ia. & Suspected implant/metastasis was benign: this led to 1 case of downstaging from stage IIIc to Ia. & No lymph node involvement: 1 presumed stage IIIc tumor was downstaged to stage Ia. Upstaging occurred only in women with serous BOT (P = 0.004). In 11 of the 14 cases of upstaging, the woman received complete staging procedures, but this was not statistically significant (P = 0.153). There was no correlation between histologic subtype and downstaging, which occurred in 3 women with serous BOT and 1 with mucinous BOT (P = 1). Table 3 shows the surgeon’s ability to identify tumor spread to the peritoneum and the contralateral ovary during surgery. Notably, the specificity and NPV were high, suggesting that it is easier to identify tissues that with certainty are normal than to identify tissues that with certainty are tumor involved. A clear correlation between histologic subtype and FIGO stage was found. Only serous tumors were more advanced than stage I tumors (P G 0.048). Noninvasive implants were found only in women with serous tumors (P = 0.017). Invasive implants and stromal microinvasion were likewise found only in women with serous tumors, but this was not significant (P = 0.617 and P = 0.479, respectively) because of very few cases. The 2 patients with invasive implants received adjuvant chemotherapy. There was no correlation between radical surgery and upstaging because of disease found in macroscopically normal-looking tissues (P = 0.437). During follow-up, 4 patients (5.3%) relapsed, resulting in a recurrence incidence of 2.2% per year. All 4 patients had recurrence of serous BOT, and all recurrences were managed surgically. These women originally had BOT in stages Ic, IIb, IIIa, and IIIb. Recurrence was associated with noninvasive implants (P = 0.019). During follow-up, 3 women died, but no deaths were related to BOT or the treatment of BOT. All deaths happened more than 30 days after the surgery. Both stage III patients with relapse experienced a second relapse; 1 with recurrence of BOT 12.1 months after the first recurrence and 1 with malignant transformation to stage IIIc serous adenocarcinoma 19.2 months after the first recurrence. Compared with radical surgery, nonradical surgery was not associated with a higher frequency of recurrence (P = 0.137). Neither complete staging nor upstaging due to microscopic findings was associated with recurrence, P = 0.638 and P = 0.172, respectively. The final histologic evaluation or the review of medical records revealed a relatively high coexistence of other malignancies. Four women were found to have an endometrial adenocarcinoma simultaneously to BOT, and 1 woman treated surgically for an endometrial adenocarcinoma was found to have BOT not previously suspected. All 5 women had a * 2014 IGCS and ESGO
Copyright © 2014 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
International Journal of Gynecological Cancer
& Volume 24, Number 5, June 2014
Surgery for Borderline Ovarian Tumors
TABLE 2. Correlation between macroscopic and microscopic findings in operations for BOT Microscopic Evaluation Macroscopic Evaluation Contralateral ovary
Negative Positive Negative Positive Negative Positive Negative Positive Negative Positive Negative Positive
Omentum Uterus Peritoneum Appendix Lymph nodes
Negative
Positive
37 4 62 0 52 1 49 4 14 0 3 4
3 22 6 0 3 0 4 9 0 0 0 0
Correlation (Fisher Exact Test)
J Statistics*
P G 0.001
0.78
V
0.00
P=1 P G 0.001
j0.03 0.62
V
V
V
0.00
Em dash indicates insufficient data. J value of greater than 0.75 means an excellent correlation, 0.4 to 0.75 means a fair/good correlation, and less than 0.4 means a moderate/poor correlation. A negative J value indicates less correlation than what would be expected by chance alone.
serous BOT. Furthermore, 1 woman had cervical cancer, 1 had a simultaneous breast cancer, and 1 had previously had breast cancer. Because the tumor types are easily separable, these patients were not excluded from the analysis.
DISCUSSION The extent of surgical treatment and staging in patients with BOT is an intensively and continuously debated topic. To the best of our knowledge, this is the largest study that specifically compares the macroscopic and microscopic findings of the uterus, the ovaries, the omentum, and multiple peritoneal surfaces during operations for a cohort of patients with BOT of different histologic subtypes. The current study shows that macroscopically normal-appearing ovary or peritoneal surfaces rarely contain microscopic disease. Similar results have been described by other authors in a smaller study and in a study regarding only serous tumors.10,11 According to this study, the presence of occult disease in the omentum in 6 cases (8%, all with serous BOT) indicates that a normal-looking omentum does not exclude the presence of microscopic implants. Leake et al11 found that 17% of patients with a macroscopically normal omentum had microscopic disease. Yazigi et al10 found a frequency of occult omental disease of 13%, and Camatte et al3 found that 5 of 56 patients treated with omentectomy had microscopic implants. Therefore, omentectomy of a macroscopically normal omentum should not be omitted in operations in which serous BOT is found at frozen section. The absence of mucinous tumors with omental disease in this study did not allow firm conclusions, but it seems that omission of omentectomy carries a negligible risk in these cases. Regarding lymphadenectomy, this study was inconclusive because of the very limited data. Other studies have
shown that lymph node involvement is seen in up to 20% of patients with BOT but also that lymph node involvement does not influence long-term survival.12,13 In the current study, the appendix appeared normal in all patients, and microscopic disease was never found. This may indicate that a macroscopically healthy-looking appendix does not contain microscopic implants, but no firm conclusion can be drawn because of the limited data in this study. Many authors recommend conservation of fertility in young women with stage I disease.5,14 In this study, no association between conservative surgery and an increased risk for recurrence was found. However, such an association has been demonstrated by other authors14Y16 who found conservative surgery to increase the risk for recurrence. The short follow-up time in the present study and differences in the definitions of radical and conservative surgery may be of influence. Given the consistency in complication rate, it seems reasonable to recommend radical surgery in the management of BOT if there is no further wish to preserve fertility. However, despite the increased risk for recurrence, other
TABLE 3. Sensitivity, specificity, PPV, and NPV of the surgeon’s ability to identify tumor spread to the contralateral ovary and the peritoneal surfaces during surgery for BOT
Sensitivity Specificity PPV NPV
Contralateral Ovary
Peritoneum
88% 90.2% 84.6% 92.5%
69.2% 92.5% 69.2% 92.5%
* 2014 IGCS and ESGO
Copyright © 2014 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
877
Kristensen et al
International Journal of Gynecological Cancer
authors report that conservative surgery does not seem to affect long-term survival.6,15 Recurrence of BOT is generally treated surgically with excellent results.5,16,17 Complete surgical staging is recommended for all patients with BOT, but in the daily practice, far from all patients are completely staged. In the current study, 61.3% of the patients were completely staged, which is a high proportion compared with other studies.18 We found no significant correlation between complete staging and upstaging because of the finding of microscopic disease. This is in contradiction to what has been shown by other authors.3,10 So far, it is unknown to which degree complete staging reduces the risk for recurrence. As in many other studies, we did not find an increased incidence of recurrence in women who received incomplete staging.19,20 In a large cohort study by du Bois et al,16 several models were tested to evaluate the effect of incomplete staging in serous BOT. They all found an approximately doubling of hazard ratio regarding progressionfree survival when incomplete staging was performed. Similarly, other authors have demonstrated an increased incidence of recurrence after incomplete staging, but, in addition, they have shown that incomplete staging does not have a negative effect on long-term survival in women with BOT.14,21 The need for complete staging in operations for BOT has to be compared with the frequency of undetected microscopic disease. In the present study, 18.7% were upstaged because of the finding of microscopic disease or positive cytology. Upon review of the literature, we found that Yazigi et al10 found 24% of patients to be upstaged after complete staging procedures, and Snider et al22 found that 18.5% presumed stage I patients were upstaged after complete staging procedures. All patients who were upstaged in this study had serous BOT, which is in accordance with other studies in which microscopic disease is most frequently found in patients with serous tumors.3,22 Complete staging is carried out to determine whether implants are present and to determine whether further treatment is indicated. The management of BOT, however, is almost always surgical and is the same for BOT in stage I as for BOT in stage III.8 Adjuvant chemotherapy can be administered to women with invasive implants because invasive implants are associated with recurrence and decreased survival.2,18 In the present study, invasive implants were never undetected during surgery for BOT. Very few authors have reported microscopic invasive implants,21,22 suggesting that invasive implants most often are visible to the surgeon. Although microscopic disease is found, this will almost never alter the choice of treatment, and all Danish patients are offered the same extent of postoperative observation regardless of tumor stage.8 Although incomplete staging did not increase the risk for recurrence in this study, it is important to consider complete staging as a preventive measure. Although recurrences are treatable and do not necessarily have negative consequences on long-term survival, recurrence (and fear of recurrence) can deteriorate the patient’s quality of life.23,24 During this study, a remarkably high frequency of endometrial cancer was found among women with serous BOT. With an incidence of 13 per 100,000 per year of endometrial
878
& Volume 24, Number 5, June 2014
cancer in Denmark,25 5 cases in 75 women in this study are higher than the expectations. All 5 had serous BOT. Whether this finding represents a coincidence or an actual association between BOT and endometrial cancer is unknown, but similar cases have been described in the literature.26 The study has a relatively short median follow-up time of 28.7 months (range, 3.8Y67.1 months), corresponding to 2.4 years. During this time, 4 patients relapsed. A longer follow-up period might have changed this number because BOTs are capable of recurrence after several years.2 One patient progressed to malignant disease (stage IIIc serous adenocarcinoma) during follow-up, giving an incidence of malignant transformation of 0.6% per year. Other studies have shown that the risk for progression to invasive carcinoma in BOT is 2% to 3%.15,16,18 Deaths related to BOT are rare27 and did not occur in the present study, which may be explained by the short follow-up period or the fact that most patients in this study had stage I disease. One of the most interesting questions regarding treatment of BOT is whether a secondary staging operation is necessary if the diagnosis of BOT is given at final histology after an operation for a presumed benign ovarian lesion. Our study suggests that no further staging is needed after removal of stage Ia mucinous BOT. Regarding the serous lesions, a staging operation including at least omentectomy is recommended, and if there is no further wish to preserve fertility, we also advise radical treatment. If there is a precise and reliable description of a normal omentum, the need for a secondary staging operation could be discussed with the patient because the risk for invasive implants is negligible, and in the event of a recurrence, it can be treated surgically with excellent results. However, one should be reluctant to change existing guidelines because of the relatively limited number of patients and the relatively short follow-up period in the present study. The large cohort study by du Bois et al16 showed that restaging surgery after initial incomplete staging does increase progression-free survival. However, they also found a 5-year survival rate after recurrence of BOT of 98%. The incidence of BOT in Denmark is 150 per year,9 limiting the number of eligible patients for a single-institution study. Compared with other studies of BOT, 75 is still a rather high number of participants.5 Because this is a retrospective study with all data originating from reviews of medical files, the description of tissues was not carried out systematically, which may bias the results. To gain more strength in a future study, we suggest performing a prospective multicenter study in which data should be collected through questionnaires filled out by the surgeon and the pathologist right after the operation and with a follow-up period of 5 to 10 years.
CONCLUSIONS In this study, we found that normal-looking ovaries or peritoneal surfaces rarely contain a microscopic focus of BOT. In 8% of cases, microscopic noninvasive implants were found in the omentum (all in patients with serous BOT). The uterine surface is rarely involved, but the macroscopic evaluation does not with certainty find noninvasive implants. * 2014 IGCS and ESGO
Copyright © 2014 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
International Journal of Gynecological Cancer
& Volume 24, Number 5, June 2014
With regard to the appendix and the lymph nodes, the study was inconclusive because of very few data.
ACKNOWLEDGMENTS The authors thank Bo Beck, MSc, civil engineer and lecturer at University of Southern Denmark, for his assistance with the biostatistics.
REFERENCES 1. Faluyi OMM, Gourley C, Bryant A, et al. Interventions for the treatment of borderline ovarian tumours. Cochrane Database Syst Rev. 2010. 2. Seidman JD, Kurman RJ. Ovarian serous borderline tumors: a critical review of the literature with emphasis on prognostic indicators. Hum Pathol. 2000;31:539Y557. 3. Camatte S, Morice P, Thoury A, et al. Impact of surgical staging in patients with macroscopic ‘‘stage I’’ ovarian borderline tumours: analysis of a continuous series of 101 cases. Eur J Cancer. 2004;40:1842Y1849. 4. Seidman JD, Soslow RA, Vang R, et al. Borderline ovarian tumors: diverse contemporary viewpoints on terminology and diagnostic criteria with illustrative images. Hum Pathol. 2004;35:918Y933. 5. Cadron I, Leunen K, Van Gorp T, et al. Management of borderline ovarian neoplasms. J Clin Oncol. 2007;25:2928Y2937. 6. Fauvet R, Poncelet C, Boccara J, et al. Fertility after conservative treatment for borderline ovarian tumors: a French multicenter study. Fertil Steril. 2005;83:284Y290; quiz 525Y526. 7. Benedet JL, Bender H, Jones H III, et al. FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. FIGO Committee on Gynecologic Oncology. Int J Gynaecol Obstet. 2000;70:209Y262. 8. DGCG Guidelines for Treatment of Ovarian Cancers. Available at: http://www.dgcg.dk/images/retningslinier% 20endelige%20ovariecancer%20juni%202012.pdf. Accessed November 18, 2013. 9. DGCG Annual Report. Available at: http://www.dgcg.dk/ ˚ rsrapport_2012_v2.pdf. Accessed images/DGCD_A November 18, 2013. 10. Yazigi R, Sandstad J, Munoz AK. Primary staging in ovarian tumors of low malignant potential. Gynecol Oncol. 1988;31:402Y408. 11. Leake JF, Currie JL, Rosenshein NB, et al. Long-term follow-up of serous ovarian tumors of low malignant potential. Gynecol Oncol. 1992;47:150Y158.
Surgery for Borderline Ovarian Tumors
12. Leake JF, Rader JS, Woodruff JD, et al. Retroperitoneal lymphatic involvement with epithelial ovarian tumors of low malignant potential. Gynecol Oncol. 1991;42:124Y130. 13. Rota SM, Zanetta G, Ieda N, et al. Clinical relevance of retroperitoneal involvement from epithelial ovarian tumors of borderline malignancy. Int J Gynecol Cancer. 1999;9:477Y480. 14. Tinelli R, Tinelli A, Tinelli FG, et al. Conservative surgery for borderline ovarian tumors: a review. Gynecol Oncol. 2006;100:185Y191. 15. Zanetta G, Rota S, Chiari S, et al. Behavior of borderline tumors with particular interest to persistence, recurrence, and progression to invasive carcinoma: a prospective study. J Clin Oncol. 2001;19:2658Y2664. 16. du Bois A, Ewald-Riegler N, de Gregorio N, et al. Borderline tumours of the ovary: a cohort study of the Arbeitsgmeinschaft Gynakologische Onkologie (AGO) Study Group. Eur J Cancer. 2013;49:1905Y1914. 17. Trope C, Davidson B, Paulsen T, et al. Diagnosis and treatment of borderline ovarian neoplasms ‘‘the state of the art’’. Eur J Gynaecol Oncol. 2009;30:471Y482. 18. Morice P, Uzan C, Fauvet R, et al. Borderline ovarian tumour: pathological diagnostic dilemma and risk factors for invasive or lethal recurrence. Lancet Oncol. 2012;13:e103Ye115. 19. Rao GG, Skinner E, Gehrig PA, et al. Surgical staging of ovarian low malignant potential tumors. Obstet Gynecol. 2004;104:261Y266. 20. Anfinan N, Sait K, Ghatage P, et al. Ten years experience in the management of borderline ovarian tumors at Tom Baker Cancer Centre. Arch Gynecol Obstet. 2011;284:731Y735. 21. Winter WE III, Kucera PR, Rodgers W, et al. Surgical staging in patients with ovarian tumors of low malignant potential. Obstet Gynecol. 2002;100:671Y676. 22. Snider DD, Stuart GC, Nation JG, et al. Evaluation of surgical staging in stage I low malignant potential ovarian tumors. Gynecol Oncol. 1991;40:129Y132. 23. Sun CC, Ramirez PT, Bodurka DC. Quality of life for patients with epithelial ovarian cancer. Nat Clin Pract Oncol. 2007;4:18Y29. 24. Meyerowitz BE, Kurita K, D’Orazio LM. The psychological and emotional fallout of cancer and its treatment. Cancer J. 2008;14:410Y413. 25. DGCG Guidelines for Treatment of Endometrial Cancer. Available at: http://www.dgcg.dk/images/retningslinier/ Corpuscancer/Endometriecancer_2010-jan.pdf. Accessed November 18, 2013. 26. Castro IM, Connell PP, Waggoner S, et al. Synchronous ovarian and endometrial malignancies. Am J Clin Oncol. 2000;23:521Y525. 27. Hart WR. Borderline epithelial tumors of the ovary. Mod Pathol. 2005;18:S33YS50.
* 2014 IGCS and ESGO
Copyright © 2014 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
879
The Value of Random Biopsies, Omentectomy, and Hysterectomy in Operations for Borderline Ovarian Tumors Gitte Schultz Kristensen, MD,* Doris Schledermann, MD,Þ Ole Mogensen, Prof, DMSci,þ and Kirsten Marie Jochumsen, MD, PhDþ
Objective: Borderline ovarian tumors (BOTs) are treated surgically like malignant ovarian tumors with hysterectomy, salpingectomy, omentectomy, and multiple random peritoneal biopsies in addition to removal of the ovaries. It is, however, unknown how often removal of macroscopically normal-appearing tissues leads to the finding of microscopic disease. To evaluate the value of random biopsies, omentectomy, and hysterectomy in operations for BOT, the macroscopic and microscopic findings in a cohort of these patients were reviewed retrospectively. Materials: Women treated for BOT at Odense University Hospital from 2007 to 2011 were eligible for this study. Data were extracted from electronic records. Intraoperative assessment of tumor spread (macroscopic disease) and the microscopic evaluation of removed tissues were the main outcome measures. Results: The study included 75 patients, 59 (78.7%) in International Federation of Gynecology and Obstetrics stage I, 9 (12%) in stage II, and 7 (9.3%) in stage III. The histologic subtypes were serous (68%), mucinous (30.7%), and Brenner type (1.3%). Macroscopically radical surgery was performed in 62 patients (82.7%), and 46 (61.3%) received complete staging. The surgeon’s identification of macroscopic tumor spread to the contralateral ovary and the peritoneum had a sensitivity of 88% and 69.2% and a specificity of 90.2% and 92.5%, respectively. The macroscopic assessment of the uterine surface, the omentum, and the pelvic and para-aortal lymph nodes was not a good predictor of microscopic disease. During follow-up, 4 patients (5.3%) relapsed with no relation to surgical radicality or the extent of staging procedures. Conclusions: Ovaries and peritoneal surfaces with a macroscopically normal appearance rarely contain a microscopic focus of BOT. Key Words: Borderline ovarian tumors, Macroscopic evaluation, Microscopic evaluation, Complete staging, Radical surgery Received November 21, 2013, and in revised form February 12, 2014. Accepted for publication March 6, 2014. (Int J Gynecol Cancer 2014;24: 874Y879)
*Emergency Department, Kolding Hospital, Kolding, Denmark; and Departments of †Pathology, and ‡Obstetrics and Gynecology, Odense University Hospital, Odense, Denmark. Address correspondence and reprint requests to Gitte Schultz Kristensen, MD, Department of Obstetrics and Gynecology, Odense University Hospital, Sdr. Boulevard 29, DK-5000 Odense C, Denmark. E-mail: [email protected]. The authors declare no conflicts of interest. Copyright * 2014 by IGCS and ESGO ISSN: 1048-891X DOI: 10.1097/IGC.0000000000000140
874
when the World Health Organization first classiI nfied1973, borderline ovarian tumors (BOTs) as a separate type
of ovarian tumor, the management of BOT was equal to that of ovarian carcinomas. Since then, a number of authors have shown that adjuvant chemotherapy and irradiation are not beneficial for women with BOT.1 Similarly, removal of pelvic and para-aortic lymph nodes has been shown not to improve long-term survival or recurrence.2,3 Recognizing that there are ovarian epithelial neoplasms that both morphologically and in natural history seem to fall
International Journal of Gynecological Cancer
& Volume 24, Number 5, June 2014
Copyright © 2014 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
International Journal of Gynecological Cancer
& Volume 24, Number 5, June 2014
between usual carcinoma and completely benign neoplasms, the term BOT was proposed. The 2 most common morphological types are serous and mucinous BOT. Grossly, most BOTs are cystic and solid with friable papillary nodules that may project into otherwise smooth-walled cysts or from the surface of the ovary. The borderline areas may make up a small percentage of the neoplasm (by definition, 910%) or may be more extensively present.4 Microscopically, most BOTs are characterized by papillary proliferations of epithelial cells exhibiting mild or at the most moderate nuclear atypia. By definition, stromal invasion is absent in BOT. Extraovarian disease in association with a serous BOT is referred to as implants and is found more frequently with tumors that have an exophytic component on the ovarian surface. Most commonly, implants are located in the omentum and on peritoneal surfaces but may also be located in regional lymph nodes. Implants are categorized as either noninvasive or invasive. Invasive implants show obvious destructive invasion recognized by irregular infiltration into underlying tissue. Separation of the implants into invasive and noninvasive subtypes carries prognostic implications because the rare fatal cases of BOT most often are those with invasive implants. In the recent years, young women with disease confined to 1 ovary have been treated more conservatively to preserve their fertility. Conservative treatment increases the risk for recurrence but has not been shown to reduce longterm survival.5,6 The International Federation of Gynecology and Obstetrics (FIGO) guidelines and the current Danish guidelines for treatment of BOT recommend surgical removal of the ovaries, the uterus, and the omentum; multiple peritoneal biopsies; and cytologic examination of peritoneal fluids. In case of a mucinous BOT, removal of the appendix is also recommended.7,8 In the latest annual report from the Danish Gynecologic Cancer Group, the overall 5-year survival after treatment of BOT in Denmark (all stages) is calculated to be 92%.9 Removal of tissues with a focus of BOTwill most likely lower the risk for recurrence, but it is unknown how often removal of a healthy-looking tissue will lead to the finding of a microscopic focus of BOT. The aim of this retrospective study was to evaluate how often microscopic disease is found in healthy-looking tissues in operations for BOT and concurrently review the need for removal of these normallooking tissues.
MATERIALS AND METHODS All women diagnosed with BOT (International Classification of Diseases, Tenth Revision, code D391A) at Odense University Hospital between January 1, 2007, and December 31, 2011, were identified through a search in the hospital’s electronic database. Patients diagnosed with BOT before 2007 who relapsed in 2007 to 2011 were not included. A total of 75 patients were eligible for this study. Patients were followed from the initial BOT diagnosis to October 2, 2012. All medical records were found in the electronic health record systems. The records were reviewed to collect data regarding age, tumor size, surgical management, and postoperative
Surgery for Borderline Ovarian Tumors
management. Macroscopic findings at primary surgery and in staging operations were recorded. Special interest was paid to the macroscopic assessment of the ovaries, the uterine serosa, the omentum, the peritoneal surfaces, the appendix, and the lymph nodes during surgery, and this was compared with the microscopic evaluation of these tissues at histologic examination. The patients were primarily staged on the basis of intraoperative findings, and their final stage was based on the surgical findings combined with the results of the histologic and cytologic examination according to the FIGO classification. Radical surgery was defined as removal of the uterus and both ovaries combined with complete staging. Complete staging procedures were defined according to the FIGO guidelines as radical surgery combined with cytologic examination of peritoneal fluids, multiple peritoneal biopsies, and omentectomy (with modification because lymph node sampling is still part of the complete staging procedures in the FIGO guidelines).7 In case of a mucinous tumor, appendectomy was also part of the complete staging procedure. Incomplete staging was defined as the lack of 1 or more of the abovementioned procedures. Lymph node sampling was not a part of the staging procedure but was performed occasionally if there was clinical or radiologic suggestion of involvement. A database was created in Epidata version 1.1.2. All statistical analyses were carried out in Stata version 12.1. Two categorical, binary variables were compared using the Fisher exact test, for example, when comparing the macroscopic and microscopic evaluation of the uterus. The W2 test was used when comparing 2 categorical variables with 2 or more categories, for example, comparing the histologic subtype with recurrence. From these tests, P values were calculated. Generally, a P value of less than 0.05 was considered to be statistically significant. The concordance between macroscopic and microscopic findings was evaluated using J statistics. The surgeon’s ability to identify tumor spread during surgery was evaluated, calculating the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The incidence of recurrence and malignant transformation was calculated. This study was approved by the Danish Health and Medicines Authority, case number 3-3013-312/1/. This study was also approved by the Danish Data Protection Agency, case number 13/7525.
RESULTS Characteristics of the 75 patients with BOTs are shown in Table 1. The results from the macroscopic and microscopic evaluation of the tissues and the concordance between the results are listed in Table 2. Table 2 does not contain data for all of the 6 types of tissues from all 75 patients. The reason for this is that the organ/tissue had already been removed (for example, the uterus or the appendix), the description of the tissue in the surgical record was insufficient, or the tissues had not been removed during surgery (for example, the appendix or the lymph nodes). Complete staging procedures were carried out in 46 women (61.3%) either at primary surgery or at a later staging operation after BOT had been diagnosed. In 29 women
* 2014 IGCS and ESGO
Copyright © 2014 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
875
International Journal of Gynecological Cancer
Kristensen et al
TABLE 1. Characteristics of the 75 patients with BOT Patient Characteristics Age, median (range), y 54 (25Y90) Histologic subtypes Serous 51 (68%) Mucinous 23 (30.7%) Brenner type 1 (1.3%) FIGO stage Stage Ia 40 (50.3%) Stage Ib 2 (2.7%) Stage Ic 17 (22.7%) Stage IIa 0 Stage IIb 7 (9.3%) Stage IIc 2 (2.7%) Stage IIIa 5 (6.7%) Stage IIIb 2 (2.7%) Stage IIIc 0 Stage IV 0 Surgery Primary 55 (73.3%) Staging surgery 19 (25.3%) Radical surgery after former 1 (1.3%) conservative surgery Radical surgery 62 (82.7%) Radical surgery, median age (range) 55 (33Y86) Conservative surgery, median age (range) 40 (25Y90) Complete staging 46 (61.3%) Tumor size, mean (range), cm 12.52 (0.6Y30) Other histologic findings Noninvasive implants 14 (18.7%) Invasive implants 2 (2.7%) Stromal microinvasion 3 (4%) Recurrence 4 (5.3%) Follow-up time, median (range), mo 28.7 (3.8Y67.1) Recurrence time, median (range), mo 22.5 (7.4Y42.3)
(38.7%), 1 or more of the staging procedures (most often concerning peritoneal sampling or the cytologic examination of peritoneal fluids) were omitted. The patients were staged before and after the results of the histologic and cytologic examination. The histologic and cytologic examinations led to upstaging in 14 cases (18.7%) and downstaging in 4 cases (5.3%). Upstaging was caused by the following: & The finding of noninvasive implants in the visceral peritoneum (not covering the internal female genitals): 5 presumed stage I tumors were upstaged to stage IIb. & The finding of noninvasive implants in the omentum: 3 presumed stage I tumors and 1 stage II tumor were upstaged to stage IIIa.
876
& Volume 24, Number 5, June 2014
& Ovarian surface growth: 2 presumed stage Ia tumors and 1 stage Ib tumor were upstaged to stage Ic. & Positive cytologic findings: 1 tumor was upstaged from stage Ib to Ic and 1 tumor was upstaged from stage IIb to IIc. Downstaging was caused by the following: & Bilateral ovarian tumors were suspected but not confirmed by histology: 2 presumed stage Ib tumors were downstaged to stage Ia. & Suspected implant/metastasis was benign: this led to 1 case of downstaging from stage IIIc to Ia. & No lymph node involvement: 1 presumed stage IIIc tumor was downstaged to stage Ia. Upstaging occurred only in women with serous BOT (P = 0.004). In 11 of the 14 cases of upstaging, the woman received complete staging procedures, but this was not statistically significant (P = 0.153). There was no correlation between histologic subtype and downstaging, which occurred in 3 women with serous BOT and 1 with mucinous BOT (P = 1). Table 3 shows the surgeon’s ability to identify tumor spread to the peritoneum and the contralateral ovary during surgery. Notably, the specificity and NPV were high, suggesting that it is easier to identify tissues that with certainty are normal than to identify tissues that with certainty are tumor involved. A clear correlation between histologic subtype and FIGO stage was found. Only serous tumors were more advanced than stage I tumors (P G 0.048). Noninvasive implants were found only in women with serous tumors (P = 0.017). Invasive implants and stromal microinvasion were likewise found only in women with serous tumors, but this was not significant (P = 0.617 and P = 0.479, respectively) because of very few cases. The 2 patients with invasive implants received adjuvant chemotherapy. There was no correlation between radical surgery and upstaging because of disease found in macroscopically normal-looking tissues (P = 0.437). During follow-up, 4 patients (5.3%) relapsed, resulting in a recurrence incidence of 2.2% per year. All 4 patients had recurrence of serous BOT, and all recurrences were managed surgically. These women originally had BOT in stages Ic, IIb, IIIa, and IIIb. Recurrence was associated with noninvasive implants (P = 0.019). During follow-up, 3 women died, but no deaths were related to BOT or the treatment of BOT. All deaths happened more than 30 days after the surgery. Both stage III patients with relapse experienced a second relapse; 1 with recurrence of BOT 12.1 months after the first recurrence and 1 with malignant transformation to stage IIIc serous adenocarcinoma 19.2 months after the first recurrence. Compared with radical surgery, nonradical surgery was not associated with a higher frequency of recurrence (P = 0.137). Neither complete staging nor upstaging due to microscopic findings was associated with recurrence, P = 0.638 and P = 0.172, respectively. The final histologic evaluation or the review of medical records revealed a relatively high coexistence of other malignancies. Four women were found to have an endometrial adenocarcinoma simultaneously to BOT, and 1 woman treated surgically for an endometrial adenocarcinoma was found to have BOT not previously suspected. All 5 women had a * 2014 IGCS and ESGO
Copyright © 2014 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
International Journal of Gynecological Cancer
& Volume 24, Number 5, June 2014
Surgery for Borderline Ovarian Tumors
TABLE 2. Correlation between macroscopic and microscopic findings in operations for BOT Microscopic Evaluation Macroscopic Evaluation Contralateral ovary
Negative Positive Negative Positive Negative Positive Negative Positive Negative Positive Negative Positive
Omentum Uterus Peritoneum Appendix Lymph nodes
Negative
Positive
37 4 62 0 52 1 49 4 14 0 3 4
3 22 6 0 3 0 4 9 0 0 0 0
Correlation (Fisher Exact Test)
J Statistics*
P G 0.001
0.78
V
0.00
P=1 P G 0.001
j0.03 0.62
V
V
V
0.00
Em dash indicates insufficient data. J value of greater than 0.75 means an excellent correlation, 0.4 to 0.75 means a fair/good correlation, and less than 0.4 means a moderate/poor correlation. A negative J value indicates less correlation than what would be expected by chance alone.
serous BOT. Furthermore, 1 woman had cervical cancer, 1 had a simultaneous breast cancer, and 1 had previously had breast cancer. Because the tumor types are easily separable, these patients were not excluded from the analysis.
DISCUSSION The extent of surgical treatment and staging in patients with BOT is an intensively and continuously debated topic. To the best of our knowledge, this is the largest study that specifically compares the macroscopic and microscopic findings of the uterus, the ovaries, the omentum, and multiple peritoneal surfaces during operations for a cohort of patients with BOT of different histologic subtypes. The current study shows that macroscopically normal-appearing ovary or peritoneal surfaces rarely contain microscopic disease. Similar results have been described by other authors in a smaller study and in a study regarding only serous tumors.10,11 According to this study, the presence of occult disease in the omentum in 6 cases (8%, all with serous BOT) indicates that a normal-looking omentum does not exclude the presence of microscopic implants. Leake et al11 found that 17% of patients with a macroscopically normal omentum had microscopic disease. Yazigi et al10 found a frequency of occult omental disease of 13%, and Camatte et al3 found that 5 of 56 patients treated with omentectomy had microscopic implants. Therefore, omentectomy of a macroscopically normal omentum should not be omitted in operations in which serous BOT is found at frozen section. The absence of mucinous tumors with omental disease in this study did not allow firm conclusions, but it seems that omission of omentectomy carries a negligible risk in these cases. Regarding lymphadenectomy, this study was inconclusive because of the very limited data. Other studies have
shown that lymph node involvement is seen in up to 20% of patients with BOT but also that lymph node involvement does not influence long-term survival.12,13 In the current study, the appendix appeared normal in all patients, and microscopic disease was never found. This may indicate that a macroscopically healthy-looking appendix does not contain microscopic implants, but no firm conclusion can be drawn because of the limited data in this study. Many authors recommend conservation of fertility in young women with stage I disease.5,14 In this study, no association between conservative surgery and an increased risk for recurrence was found. However, such an association has been demonstrated by other authors14Y16 who found conservative surgery to increase the risk for recurrence. The short follow-up time in the present study and differences in the definitions of radical and conservative surgery may be of influence. Given the consistency in complication rate, it seems reasonable to recommend radical surgery in the management of BOT if there is no further wish to preserve fertility. However, despite the increased risk for recurrence, other
TABLE 3. Sensitivity, specificity, PPV, and NPV of the surgeon’s ability to identify tumor spread to the contralateral ovary and the peritoneal surfaces during surgery for BOT
Sensitivity Specificity PPV NPV
Contralateral Ovary
Peritoneum
88% 90.2% 84.6% 92.5%
69.2% 92.5% 69.2% 92.5%
* 2014 IGCS and ESGO
Copyright © 2014 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
877
Kristensen et al
International Journal of Gynecological Cancer
authors report that conservative surgery does not seem to affect long-term survival.6,15 Recurrence of BOT is generally treated surgically with excellent results.5,16,17 Complete surgical staging is recommended for all patients with BOT, but in the daily practice, far from all patients are completely staged. In the current study, 61.3% of the patients were completely staged, which is a high proportion compared with other studies.18 We found no significant correlation between complete staging and upstaging because of the finding of microscopic disease. This is in contradiction to what has been shown by other authors.3,10 So far, it is unknown to which degree complete staging reduces the risk for recurrence. As in many other studies, we did not find an increased incidence of recurrence in women who received incomplete staging.19,20 In a large cohort study by du Bois et al,16 several models were tested to evaluate the effect of incomplete staging in serous BOT. They all found an approximately doubling of hazard ratio regarding progressionfree survival when incomplete staging was performed. Similarly, other authors have demonstrated an increased incidence of recurrence after incomplete staging, but, in addition, they have shown that incomplete staging does not have a negative effect on long-term survival in women with BOT.14,21 The need for complete staging in operations for BOT has to be compared with the frequency of undetected microscopic disease. In the present study, 18.7% were upstaged because of the finding of microscopic disease or positive cytology. Upon review of the literature, we found that Yazigi et al10 found 24% of patients to be upstaged after complete staging procedures, and Snider et al22 found that 18.5% presumed stage I patients were upstaged after complete staging procedures. All patients who were upstaged in this study had serous BOT, which is in accordance with other studies in which microscopic disease is most frequently found in patients with serous tumors.3,22 Complete staging is carried out to determine whether implants are present and to determine whether further treatment is indicated. The management of BOT, however, is almost always surgical and is the same for BOT in stage I as for BOT in stage III.8 Adjuvant chemotherapy can be administered to women with invasive implants because invasive implants are associated with recurrence and decreased survival.2,18 In the present study, invasive implants were never undetected during surgery for BOT. Very few authors have reported microscopic invasive implants,21,22 suggesting that invasive implants most often are visible to the surgeon. Although microscopic disease is found, this will almost never alter the choice of treatment, and all Danish patients are offered the same extent of postoperative observation regardless of tumor stage.8 Although incomplete staging did not increase the risk for recurrence in this study, it is important to consider complete staging as a preventive measure. Although recurrences are treatable and do not necessarily have negative consequences on long-term survival, recurrence (and fear of recurrence) can deteriorate the patient’s quality of life.23,24 During this study, a remarkably high frequency of endometrial cancer was found among women with serous BOT. With an incidence of 13 per 100,000 per year of endometrial
878
& Volume 24, Number 5, June 2014
cancer in Denmark,25 5 cases in 75 women in this study are higher than the expectations. All 5 had serous BOT. Whether this finding represents a coincidence or an actual association between BOT and endometrial cancer is unknown, but similar cases have been described in the literature.26 The study has a relatively short median follow-up time of 28.7 months (range, 3.8Y67.1 months), corresponding to 2.4 years. During this time, 4 patients relapsed. A longer follow-up period might have changed this number because BOTs are capable of recurrence after several years.2 One patient progressed to malignant disease (stage IIIc serous adenocarcinoma) during follow-up, giving an incidence of malignant transformation of 0.6% per year. Other studies have shown that the risk for progression to invasive carcinoma in BOT is 2% to 3%.15,16,18 Deaths related to BOT are rare27 and did not occur in the present study, which may be explained by the short follow-up period or the fact that most patients in this study had stage I disease. One of the most interesting questions regarding treatment of BOT is whether a secondary staging operation is necessary if the diagnosis of BOT is given at final histology after an operation for a presumed benign ovarian lesion. Our study suggests that no further staging is needed after removal of stage Ia mucinous BOT. Regarding the serous lesions, a staging operation including at least omentectomy is recommended, and if there is no further wish to preserve fertility, we also advise radical treatment. If there is a precise and reliable description of a normal omentum, the need for a secondary staging operation could be discussed with the patient because the risk for invasive implants is negligible, and in the event of a recurrence, it can be treated surgically with excellent results. However, one should be reluctant to change existing guidelines because of the relatively limited number of patients and the relatively short follow-up period in the present study. The large cohort study by du Bois et al16 showed that restaging surgery after initial incomplete staging does increase progression-free survival. However, they also found a 5-year survival rate after recurrence of BOT of 98%. The incidence of BOT in Denmark is 150 per year,9 limiting the number of eligible patients for a single-institution study. Compared with other studies of BOT, 75 is still a rather high number of participants.5 Because this is a retrospective study with all data originating from reviews of medical files, the description of tissues was not carried out systematically, which may bias the results. To gain more strength in a future study, we suggest performing a prospective multicenter study in which data should be collected through questionnaires filled out by the surgeon and the pathologist right after the operation and with a follow-up period of 5 to 10 years.
CONCLUSIONS In this study, we found that normal-looking ovaries or peritoneal surfaces rarely contain a microscopic focus of BOT. In 8% of cases, microscopic noninvasive implants were found in the omentum (all in patients with serous BOT). The uterine surface is rarely involved, but the macroscopic evaluation does not with certainty find noninvasive implants. * 2014 IGCS and ESGO
Copyright © 2014 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
International Journal of Gynecological Cancer
& Volume 24, Number 5, June 2014
With regard to the appendix and the lymph nodes, the study was inconclusive because of very few data.
ACKNOWLEDGMENTS The authors thank Bo Beck, MSc, civil engineer and lecturer at University of Southern Denmark, for his assistance with the biostatistics.
REFERENCES 1. Faluyi OMM, Gourley C, Bryant A, et al. Interventions for the treatment of borderline ovarian tumours. Cochrane Database Syst Rev. 2010. 2. Seidman JD, Kurman RJ. Ovarian serous borderline tumors: a critical review of the literature with emphasis on prognostic indicators. Hum Pathol. 2000;31:539Y557. 3. Camatte S, Morice P, Thoury A, et al. Impact of surgical staging in patients with macroscopic ‘‘stage I’’ ovarian borderline tumours: analysis of a continuous series of 101 cases. Eur J Cancer. 2004;40:1842Y1849. 4. Seidman JD, Soslow RA, Vang R, et al. Borderline ovarian tumors: diverse contemporary viewpoints on terminology and diagnostic criteria with illustrative images. Hum Pathol. 2004;35:918Y933. 5. Cadron I, Leunen K, Van Gorp T, et al. Management of borderline ovarian neoplasms. J Clin Oncol. 2007;25:2928Y2937. 6. Fauvet R, Poncelet C, Boccara J, et al. Fertility after conservative treatment for borderline ovarian tumors: a French multicenter study. Fertil Steril. 2005;83:284Y290; quiz 525Y526. 7. Benedet JL, Bender H, Jones H III, et al. FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. FIGO Committee on Gynecologic Oncology. Int J Gynaecol Obstet. 2000;70:209Y262. 8. DGCG Guidelines for Treatment of Ovarian Cancers. Available at: http://www.dgcg.dk/images/retningslinier% 20endelige%20ovariecancer%20juni%202012.pdf. Accessed November 18, 2013. 9. DGCG Annual Report. Available at: http://www.dgcg.dk/ ˚ rsrapport_2012_v2.pdf. Accessed images/DGCD_A November 18, 2013. 10. Yazigi R, Sandstad J, Munoz AK. Primary staging in ovarian tumors of low malignant potential. Gynecol Oncol. 1988;31:402Y408. 11. Leake JF, Currie JL, Rosenshein NB, et al. Long-term follow-up of serous ovarian tumors of low malignant potential. Gynecol Oncol. 1992;47:150Y158.
Surgery for Borderline Ovarian Tumors
12. Leake JF, Rader JS, Woodruff JD, et al. Retroperitoneal lymphatic involvement with epithelial ovarian tumors of low malignant potential. Gynecol Oncol. 1991;42:124Y130. 13. Rota SM, Zanetta G, Ieda N, et al. Clinical relevance of retroperitoneal involvement from epithelial ovarian tumors of borderline malignancy. Int J Gynecol Cancer. 1999;9:477Y480. 14. Tinelli R, Tinelli A, Tinelli FG, et al. Conservative surgery for borderline ovarian tumors: a review. Gynecol Oncol. 2006;100:185Y191. 15. Zanetta G, Rota S, Chiari S, et al. Behavior of borderline tumors with particular interest to persistence, recurrence, and progression to invasive carcinoma: a prospective study. J Clin Oncol. 2001;19:2658Y2664. 16. du Bois A, Ewald-Riegler N, de Gregorio N, et al. Borderline tumours of the ovary: a cohort study of the Arbeitsgmeinschaft Gynakologische Onkologie (AGO) Study Group. Eur J Cancer. 2013;49:1905Y1914. 17. Trope C, Davidson B, Paulsen T, et al. Diagnosis and treatment of borderline ovarian neoplasms ‘‘the state of the art’’. Eur J Gynaecol Oncol. 2009;30:471Y482. 18. Morice P, Uzan C, Fauvet R, et al. Borderline ovarian tumour: pathological diagnostic dilemma and risk factors for invasive or lethal recurrence. Lancet Oncol. 2012;13:e103Ye115. 19. Rao GG, Skinner E, Gehrig PA, et al. Surgical staging of ovarian low malignant potential tumors. Obstet Gynecol. 2004;104:261Y266. 20. Anfinan N, Sait K, Ghatage P, et al. Ten years experience in the management of borderline ovarian tumors at Tom Baker Cancer Centre. Arch Gynecol Obstet. 2011;284:731Y735. 21. Winter WE III, Kucera PR, Rodgers W, et al. Surgical staging in patients with ovarian tumors of low malignant potential. Obstet Gynecol. 2002;100:671Y676. 22. Snider DD, Stuart GC, Nation JG, et al. Evaluation of surgical staging in stage I low malignant potential ovarian tumors. Gynecol Oncol. 1991;40:129Y132. 23. Sun CC, Ramirez PT, Bodurka DC. Quality of life for patients with epithelial ovarian cancer. Nat Clin Pract Oncol. 2007;4:18Y29. 24. Meyerowitz BE, Kurita K, D’Orazio LM. The psychological and emotional fallout of cancer and its treatment. Cancer J. 2008;14:410Y413. 25. DGCG Guidelines for Treatment of Endometrial Cancer. Available at: http://www.dgcg.dk/images/retningslinier/ Corpuscancer/Endometriecancer_2010-jan.pdf. Accessed November 18, 2013. 26. Castro IM, Connell PP, Waggoner S, et al. Synchronous ovarian and endometrial malignancies. Am J Clin Oncol. 2000;23:521Y525. 27. Hart WR. Borderline epithelial tumors of the ovary. Mod Pathol. 2005;18:S33YS50.
* 2014 IGCS and ESGO
Copyright © 2014 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
879
