Ten years experience in the management of borderline ovarian


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Ten years experience in the management of borderline ovarian

  1. 1. Arch Gynecol Obstet (2011) 284:731–735 DOI 10.1007/s00404-010-1713-9 123 GYNECOLOGIC ONCOLOGY Ten years experience in the management of borderline ovarian tumors at Tom Baker Cancer Centre Nisrin AnWnan · Khalid Sait · Prafull Ghatage · Jill Nation · Pam Chu Received: 22 July 2010 / Accepted: 28 September 2010 / Published online: 21 October 2010 © Springer-Verlag 2010 Abstract Objective The aim of this study was to review the clinical outcomes of patients with borderline ovarian tumors (BOTs) at Tom Baker Cancer Centre (TBCC) and to assess the value of surgical staging. Methods This retrospective study included 138 patients treated for BOTs at TBCC between January 1994 and December 2005. Patients were divided into two groups: group I with complete surgical staging (n = 89) and group II with incomplete surgical staging (n = 49). This popula- tion-based study identiWed patients using the Alberta Can- cer Registry. Charts were reviewed by a single person. Data extracted included demographic information and prognos- tic factors such as age, histological type, laterality of the cyst, presence of microinvasion, and the type of surgical procedure. Data were extracted and entered into a study database for analysis. Overall survival and overall recur- rence-free survival of both groups were calculated using the Kaplan–Meier method. Risk factors for recurrence were analyzed using Cox regression analysis. Results A total of 138 patients were enrolled, with a mean age of 46 years. The median follow-up time was 37 months. The most common histological type of BOT was the serous type found in 70 (50.7%) patients. Microinvasion was identiWed in four (2.9%) patients. Twelve patients were found to have implants as result of the staging procedure; two of them were invasive implants and both required chemotherapy. Forty-three (31%) patients had conservative surgery and 95 (68.8%) patients had non-conservative sur- gery. Nine (6.5%) patients experienced recurrence: Wve (5.6%) patients in group I versus four (8.2%) patients in group II. The presence of microinvasion is the risk factor for recurrence (P = 0.013). Conclusions The indications for restaging surgery remain controversial, as there was no diVerence in recurrence rates observed between the study groups. However, surgical staging is important for identifying invasive extraovarian implants that need to be treated with chemotherapy. For patients who have conservative surgery, close- and long- term follow-up is required. Keywords Borderline ovarian tumor · Recurrence · Survival Introduction Borderline ovarian tumors (BOTs) account for 10–20% of ovarian epithelial tumors [1, 2], with the highest frequency of these tumors occurring in women with a desire to pre- serve fertility [1]. The need for complete surgical staging of BOTs is controversial; the frequency of upstaging of the tumor when a comprehensive staging procedure is per- formed ranges from 12 to 47% [3, 4]. The overall risk of recurrence after conservative surgery for a BOT ranges from 7 to 30% [5] and recurrences typically show border- line histology [6]. The rates of recurrence following both conservative and complete surgical procedures for BOTs have been reported to range between 9 and 11.6%. Disease- free and overall survival rates for the two approaches did N. AnWnan (&) · P. Ghatage · J. Nation · P. Chu Department of Gynecology Oncology, Tom Baker Cancer Centre, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada e-mail: Dr_nisreen2001@yahoo.com K. Sait Department of Obstetrics and Gynecology, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
  2. 2. 732 Arch Gynecol Obstet (2011) 284:731–735 123 not signiWcantly diVer [7]. There has been no randomized controlled trial that has evaluated the role of surgical stag- ing of BOTs. The aim of this study was to review our clini- cal experience with BOTs and to assess the value of surgical staging. Materials and methods This is a retrospective study of women treated for BOTs between January 1995 and December 2005 at Tom Baker Cancer Centre (TBCC). This population-based study identi- Wed all Southern Alberta patients with a BOT during this time period. Most of the information related to the cases was obtained using an electronic cancer registry. A chart review was performed by a single person when the elec- tronic data were incomplete. The data extracted included demographic information and prognostic factors such as age, histological type, laterality of the cyst, presence of microinvasion, type of surgical procedure (conservative vs. non-conservative surgery), and whether the patient had undergone complete or incomplete surgical staging. The histological criteria used for the diagnosis of BOTs were according to Scully et al. [8] and included (1) stratiW- cation of the epithelial lining, (2) the presence of micro- scopic papillary projections, (3) nuclear atypia; and 4) the absence of stromal invasion. At the time of diagnosis, gyne- cological pathologists reviewed the pathology from all of the patients at the gynecology tumor board. We followed the FIGO 1987 guidelines [9] for com- plete surgical staging that are used for ovarian malignan- cies; they include careful inspection of all peritoneal surfaces and peritoneal washing, infracolic omentectomy, multiple peritoneal biopsies, and pelvic and para-aortic lymphadenectomy [9]. Incomplete staging was deWned as the lack of at least one of the above-mentioned proce- dures. Surgical treatment of a BOT consisted either of conser- vative surgery (preserving the uterus and salvaging at least one ovary) or non-conservative surgery (bilateral salpingo- oophorectomy with or without hysterectomy). Inclusion criteria All patients diagnosed with a BOT were included. Patients with invasive implants found on Wnal pathology were also included. Exclusion criteria All patients diagnosed with invasive disease on Wnal pathology or patients who developed other malignancies during follow up were excluded. Study groups Patients with BOTs were divided into two groups: group I complete surgical staging and group II incomplete surgical staging. Statistical analysis Statistical analysis was performed using the statistical package of social science version, 10 (SPSS). Qualitative data were presented in the form of numbers and percent- ages. Chi-square test was used for comparison of qualita- tive data, Yates correction was used when appropriate. Overall survival (OS) and recurrence-free survival (RFS) of both groups were calculated using log-rank test. Cox regression was used to identify the risk factor for recur- rence. Results One hundred and thirty-eight patients who met the inclu- sion criteria were included in this study. The median age of the patients at the time of diagnosis was 46 years (range 16–80 years), and the median follow-up time was 37 months (range 39–154 months). The total numbers of patients in group 1 and group 2 were 89 (64.4%), 49 (35.6%), respectively. The most common histological type of tumor was the serous type, which was found in 70 (50.7%) patients; 45 (32.6%) patients had mucinous type tumors. Microinvasion was identiWed in four (2.9%) cases (Table 1). Only one patient (0.7%) found to have micro papillary pattern. Complete surgical staging was performed in 89 (64.4%) patients (group I); 12 (13.5%) had conservative surgery, while 77 of these patients (86.5%) had non-conservative surgery (Table 2). Table 1 Characteristics of 138 patients according to treatment group Group I complete staging, Group II incomplete staging Group I (n = 89) Group II (n = 49) SigniWcance (P) Age (year) 47.2 § 14.22 44.22 § 15.07 0.21 Histological type Serous 52 (58.4%) 18 (36.7%) <0.001 Mucinous 19 (21.3%) 26 (53.1%) Other 18 (20.2%) 5 (10.2%) 0.55 Microinvasion 3 (3.4%) 1 (2%) Conservative surgery 12 (13.5%) 31 (63.2%) <0.001 Non-conservative surgery 77 (86.5%) 18 (36.7%) <0.001 Frozen section 69 (77.5%) 24 (48.9%) 0.006
  3. 3. Arch Gynecol Obstet (2011) 284:731–735 733 123 In group I, 63 (70.8%) patients had an initial full staging operation, while 26 (29.2%) of them underwent a second laparotomy for a restaging procedure (Table 3). Following the initial staging procedure, tumors in 29 (46%) patients were upstaged (Table 3), the numbers and percentages of patients with Stages I, II, and III disease were 57 (64%), 13 (14.6%), and 19 (21.3%), respectively. The total number of implants identiWed during the initial staging procedure was 12 (8.6%); non-invasive implants were found in 10 (15.9%) patients, consisting of 6 in the peritoneum and 4 in the pelvic lymph nodes; 2 (3.2%) patients were found to have separate invasive implants in the peritoneum and in a pelvic lymph node. Both patients received adjuvant chemotherapy in the form of paclitaxel (Taxol) and carboplatinum for six cycles. Neither patient experienced recurrence or died. Among patients who had the restaging procedure (n = 26), upstaging of tumors was found in 14 (53.8%) cases (Table 3). No invasive implants were detected. A total of nine (6.5%) patients experienced recurrence of the disease for both groups (Table 4). Their average age was 50 years (range 38–80 years), and the median time until recurrence was 32 months (range 4–88 months). Five (5.6%) patients in group I and four (8.2%) patients in group II experienced recurrence. Table 5 shows details of the patients who developed a recurrence. The pathology in seven (77.7%) patients revealed a serous type of tumor. All patients with a recurrence were treated with a second radical surgery; three patients required adjuvant chemother- apy in the form of carboplatinum and paclitaxel (Taxol). The Wrst patient was 54-year-old woman treated initially with total abdominal hysterectomy and bilateral salpingo- oophorectomy (TAHBSO). Four years later, she developed a pelvic recurrence, and she underwent a second laparot- omy followed by chemotherapy for this invasive recur- rence. The second patient was a 38-year-old woman diagnosed with a stage Ia endometrioid BOT. She under- went initial radical surgery, but 3 years later, she developed a recurrence with invasive adenocarcinoma at the vaginal vault. She was treated with a second debulking surgery fol- lowed by six cycles of carboplatinum and paclitaxel (Taxol). The overall survival (OS) rate in groups I, II were (100%) and (98.2%), respectively (P = 0.56; Fig. 1). No statistically signiWcant diVerence in RFS rates existed between group I (94.3%) and group II (91.8%) at this time point (P = 0.53; Fig. 2). A cox model for RFS showed the presence of microinva- sion is the risk factor for recurrence P = 0.013, Exp(B) = 57.7, CI (2.32–1398), other variables (age, site of tumor, histopathology) were non-signiWcant for recurrence. Discussion The usual treatment for an apparently early stage BOT is hysterectomy with bilateral salpingo-oophorectomy. How- ever, conservative surgery is performed in young patients with surgical staging if they wish to maintain their fertility [10]. It is estimated that the rate of recurrence after conser- vative surgery is between 0 and 20% and is especially higher in patients who undergo cystectomy. In our series, conservative surgery was performed in 43 (31%) patients, with 38 (27.5%) patients treated with unilateral salpingo- oophorectomy. Five patients who underwent conservative surgery developed a recurrence, but only three patients had bilateral adnexal masses; their initial surgery was unilateral salpingo-oophorectomy and cystectomy of the contralateral ovary. Only two patients had a cystectomy as conservative surgery. Neither of them had staging procedures, and no recurrences were reported in these patients. Although conservative surgery can be performed in a patient with a stage II, III, or IV BOT who has not com- pleted childbearing, resection of extraovarian macroscopic and microscopic disease with preservation of fertility is important to achieve a good outcome [11, 12]. The need for Table 2 Breakdown of operations performed for BOTs BOTs borderline ovarian tumors, THBSO total hysterectomy and bilat- eral salpingo-oophorectomy, USO unilateral salpingo-oophorectomy Type of surgery Group I (n = 89) Group II (n = 49) SigniWcance (P) Non-conservative 77 (86.5%) 18 (36.7%) <0.001 Conservative 12 (13.5%) 31 (63.2%) <0.001 Cystectomy 0 2 (4.1%) 0.12 USO, cystectomy 0 3 (6.1%) 0.042 USO 12 (13.5%) 26 (53.1%) <0.001 Table 3 Upstaging after initial staging and restaging procedures and presence of invasive implants P = 0.60 Type of surgery Patient no. Upstaging Presence of invasive implants Initial full staging 63 (70.8%) 29 (46%) 2 (3.2%) Restaging 26 (29.2%) 14 (53.8%) 0 Table 4 Recurrence in groups I and II according to the type of surgery Group I (n = 89) Group I (n = 49) SigniWcance (P) Complete 3 (3.3%) 1 (2%) 0.55 Conservative 2 (2.2%) 3 (6.1%) 0.23
  4. 4. 734 Arch Gynecol Obstet (2011) 284:731–735 123 complete surgical staging is controversial [10, 13–15], especially in the absence of gross extraovarian disease, as no signiWcant diVerences in outcome measures of recur- rence and mortality between staged and unstaged patients have been observed [4, 16–18]. In our study, staging did not inXuence overall rates of recurrence and survival. Restaging of patients who are referred after a diagnosis of BOT may not change their overall prognosis, especially if they have undergone an initial comprehensive staging procedure with an upstaging rate between 12 and 47% [3, 4]. In 26 (18.8%) patients who underwent a second surgery for restaging, the rate of upstaging was 53.8%. Stromal microinvasion with ovarian BOTs usually asso- ciated with favorable outcome [19], certain patients with microinvasion may be at higher risk for recurrence as inva- sive disease [20]. The low prognostic utility of lymph node sampling was illustrated in a meta-analysis of 97 studies that included more than 4,000 patients with BOTs. The authors reported 98% survival in women with lymph node involvement (the incidence of pelvic lymph node involvement was 1.7%) [21]. We report Wve (3.6%) patients with pelvic lymph node involvement. One patient received chemotherapy for an invasive implant. None of the patients developed a recur- rence or died. Our policy at TBCC for the management of BOTs is as follows: if the patient is referred for an ovarian mass and frozen section shows a BOT, oophorectomy and a full stag- ing procedure are usually performed if the patient wants to preserve her fertility. However, if she has completed her family, then complete surgery with a staging procedure will Table 5 Details of patients who developed a recurrence TAH total abdominal hysterectomy, USO unilateral salpingo-oophorectomy, TAHBSO total abdominal hysterectomy and bilateral salpingo- oophorectomy, BSO bilateral salpingo-oophorectomy a Previous hysterectomy b Presence of microinvasion Age (years) Initial surgery Formal staging Pathology Treatment for recurrence 38 USO No Serous TAH, USO 45 USO Yes Serous TAH, USO 54 TAHBSO Yes Serous Debulking + chemotherapy 80 BSO No Mucinous Debulking 30 USO No Serous Debulking + chemotherapy 36 USO, cystectomya Yes Serous Debulking 53 USO No Serous Debulking 41 USO Yes Serous Debulking 38 TAH, USO Yes Endometrioidb Debulking + chemotherapy Fig. 1 Kaplan–Meier survival curves showing overall survival of pa- tients with borderline ovarian tumors who underwent complete staging (group I) versus incomplete staging (group II) (P = 0.56) Log Rank test P= 0.56 Duration of survival (months) 96847260483624120 CumSurvival 1.00 .99 .98 .97 .96 .95 .94 .93 GROUPS 2 1 Fig. 2 Kaplan–Meier survival curves showing overall recurrence-free survival of patients with borderline ovarian tumors who underwent complete staging (group I) versus incomplete staging (group II) (P = 0.53) Log Rank test P=0.53 Duration of free recurrance 96847260483624120 CumSurvival 1.00 .99 .98 .97 .96 .95 .94 .93 .92 .91 .90 GROUP 2 1
  5. 5. Arch Gynecol Obstet (2011) 284:731–735 735 123 be carried out. In a patient who is referred to us with a diag- nosis of BOT after conservative surgery, close follow-up is needed if she wishes to preserve her fertility. Otherwise, she will be counseled to undergo total hysterectomy and a staging procedure. Chemotherapy is considered if the Wnal pathology shows invasive implants. In conclusion, the indications for restaging surgery remain controversial, as no diVerence in recurrence rates was observed between the two study groups. However, sur- gical staging is important for identifying invasive extrao- varian implants that can adversely aVect the prognosis. For patients who have not had conservative surgery or staging, close- and long-term follow-up is needed. A randomized controlled trial that addresses the need for surgical staging of BOTs is warranted. ConXict of interest None. References 1. Gotlieb WH, Flikker S, Davidson B, Korach Y, Kopolovic J, Ben-Baruch G (1998) Borderline tumors of the ovary: fertility treatment, conservative management, and pregnancy outcome. Cancer 82:141–146 2. Kennedy AW, Hart RH (1996) Ovarian papillary serous tumors of low malignant potential (serous borderline tumors): a long term follow-up study, including patients with microinvasion, lymph node metastasis, and transformation to invasive serous carcinoma. Cancer 78:278–286 3. Gershenson DM (2002) Clinical management potential tumours of low malignancy. Best Pract Res Clin Obstet Gynaecol 16:513–527 4. Fauvet R, Boccara J, Dufournet C, David-MonteWore E, Poncelet C, Darai E (2004) Restaging surgery for women with borderline ovarian tumors: results of a French multicenter study. Cancer 100:1145–1151 5. Boran N, Cil AP, Tulunay G, Ozturkoglu E, Koc S, Bulbul D, Kose MF (2005) Fertility and recurrence results of conservative surgery for borderline ovarian tumors. Gynecol Oncol 97:845–851 6. Morice P, Camette S, El Hassan J, Pautier P, Duvillard P, Cas- taigne D (2001) Clinical outcomes and fertility after conservative treatment of ovarian borderline tumors. Fertil Steril 75:92–96 7. Ayhan A, Celik H, Taskiran C, Bozdag G, Aksu T (2003) Onco- logic and reproductive outcome after fertility-saving surgery in ovarian cancer. Eur J Gynaecol Oncol 24:223–232 8. Scully RE (1982) Common epithelial tumors of borderline malig- nancy (carcinomas of low malignant potential). Bull Cancer 69:228–238 9. International Federation of Gynecology and Obstetrics (1987) Changes in deWnitions of clinical staging for carcinoma of the cer- vix and ovary. Am J Obstet Gynecol 156:263–264 10. Trope C, Kaern J (1998) Management of borderline tumors of the ovary: state of the art. Semin Oncol 25:372–380 11. Gershenson DM, Silva EG, Tortolero-Luna G, Levenback C, Mor- ris M, Tornos C (1998) Serous borderline tumor of the ovary with noninvasive peritoneal implants. Cancer 83:2157–2163 12. Gershenson DM, Silva EG, Levy L, Burke TW, Wolf JK, Tornos C (1998) Ovarian serous borderline tumors with invasive perito- neal implants. Cancer 82:1096–1103 13. Leake JF, Currie JL, Rosenshein NB, WoodruV JD (1992) Long- term follow-up of serous ovarian tumors of low malignant poten- tial. Gynecol Oncol 47:150–158 14. Tazelaar HD, Bostwick DG, Ballon SC, Hendrickson MR, Kemp- son RL (1985) Conservative treatment of borderline ovarian tumors. Obstet Gynecol 66:417–422 15. Casey AC, Bell DA, Lage JM, Fuller AF, Nikrui N, Rice LW (1993) Epithelial ovarian tumors of borderline malignancy: long- term follow-up. Gynecol Oncol 50:316–322 16. Camatte S, Morice P, Thoury A, Fourchotte V, Pautier P, Lhomme C, Duvillard P, Castaigne D (2004) Impact of surgical staging in patients with macroscopic “stage I” ovarian borderline tumours: analysis of a continuous series of 101 cases. Eur J Cancer 40:1842–1849 17. Winter WE 3rd, Kucera PR, Rodgers W, McBroom JW, Olsen C, Maxwell GL (2002) Surgical staging in patients with ovarian tumors of low malignant potential. Obstet Gynecol 100:671–676 18. Trimble CL, Kosary C, Trimble EL (2002) Long-term survival and patterns of care in women with ovarian tumors of low malignant potential. Gynecol Oncol 86:34–37 19. Bell DA, Scully RE (1990) Ovarian serous borderline tumors with stromal microinvasion: a report of 21 cases. Hum Pathol 21:397– 403 20. Buttin BM, Herzog TJ, Powell MA, Rader JS, Mutch DG (2002) Epithelial ovarian tumors of low malignant potential: the role of microinvasion. Obstet Gynecol 99(1):11–17 21. Seidman JD, Kurman RJ (2000) Ovarian serous borderline tumors: a critical review of the literature with emphasis on prognostic indi- cators. Hum Pathol 31:539–557