Patterns of care and outcome in elderly cervical cancer patients: a special focus on brachytherapy.

BACKGROUND: The mean age of the general population has been prolonged and the incidence of cancer in elderly patients has increased. The purpose was to evaluate outcome of brachytherapy (BT) as an integrated part of the treatment of elderly patients with cervical cancer. PATIENTS AND METHODS: From November 1997 to January 2006, 1073 patients diagnosed with uterine cervical cancer with stages I-IV (FIGO) have completed BT at the Institut Gustave Roussy. A retrospective analysis was carried out with 113 patients aged over 70-year-old treated by conventional low dose rate (LDR) BT as a part of their treatment. RESULTS: The median age was 76 years (range, 70.7-94.4). Eighty-four percent of the patients presented a squamous cell carcinoma. Fifty-two percent of the patients were treated by a sequence excluding surgery. The mean 15 and 60 Gy treated volumes were 235 cm(3) (range, 30-371) and 138 cm(3) (range, 81-234), respectively. For the 15 Gy treated volume, the mean ICRU bladder and rectal points were 18.5 Gy (range, 6-35) and 33 Gy (range, 5-63), respectively. For the 60 Gy treated volume, the mean ICRU bladder and rectal points were 33 Gy (range, 12-64) and 41 Gy (range, 23-65), respectively. Rectal, small bowel and urinary tract complications were observed in 25 (22.1%), 5 (4.4%), and in 16 patients (14.2%), respectively. Rectal complications Grades I/II, III/IV and V (fatal) crude incidences were 19.4% (22/113), 1.8% (2/113) and 0.9% (1/113), respectively. Acute toxicity death occurred in one patient with major diarrhea associated with a hemodynamic shock. Small bowel complications Grades I/II and III/IV crude incidences were 3.5% (4/113) and 0.9% (1/113), respectively. Urinary tract complications Grades I/II and III/IV crude incidences were 11.5% (13/113) and 2.7% (3/113), respectively. With a median follow-up of 3.1 years, 10 patients developed distant metastases and 10 others presented local relapses. The 3-year specific overall survival rate was 88.6% (95%CI, 77-92) and the corresponding disease-free survival rate was 81% (95%CI, 72-88). CONCLUSIONS: Elderly women with cervical cancer tolerated BT well and had excellent local disease-free and specific survival rates. Age did not influence the effectiveness of BT in elderly patients and BT should be considered whenever possible, even in elderly patients presenting with a cervix cancer.

Should pelvic and para-aortic lymphadenectomy be different depending on histological subtype in epithelial ovarian cancer?

BACKGROUND: The aim of this study was to determine the influence of the different histological subtypes (serous versus non-serous) on the location of nodal metastases in patients undergoing pelvic and para-aortic lymphadenectomies during the initial management of epithelial ovarian tumors. METHODS: We carried out a retrospective analysis of data concerning patients fulfilling the following inclusion criteria: (1) an epithelial ovarian tumor; (2) a complete pelvic and bilateral para-aortic lymphadenectomy up to the level of the left renal vein; (3) surgical procedures including lymphadenectomies performed before adjuvant chemotherapy; and (4) a description of the distribution of positive nodes removed between pelvic and para-aortic areas. Patients were classified into two groups according to the histological subtypes: serous (group 1) and non-serous (group 2) tumors. RESULTS: Of patients treated between 1989 and 2005, 148 fulfilled the inclusion criteria: 73 had a serous tumor and 75 a non-serous tumor. Positive nodes were observed in 70 (47%) patients-47 (64%) in group 1 and 23 (31%) in group 2 (P < 0.05). But the distribution of involved nodes between pelvic and para-aortic areas in patients with positive nodes was not statistically different between the two groups. In both groups, the most common site for positive nodes in the para-aortic area was the left para-aortic group: 74% in group 1 and 61% in group 2 (NS). CONCLUSIONS: This series suggests that the histological subtype has no impact on the distribution of positive nodes in pelvic and para-aortic areas in patients with epithelial ovarian tumors.

Para-aortic involvement and interest of para-aortic lymphadenectomy after chemoradiation therapy in patients with stage IB2 and II cervical carcinoma radiologically confined to the pelvic cavity.

BACKGROUND: Pelvic radiation therapy with concomitant chemotherapy (PCRT) is the standard treatment of stage IB2/II cervical carcinoma. The impact of concomitant chemotherapy on positive para-aortic nodes (PA+), however, remains unknown. The aim of this study was twofold: to evaluate the rate of histological PA+ after PCRT and to determine the survival of patients with PA+. METHODS: Patients fulfilling the following inclusion criteria were studied: (1) stage IB2/II cervical carcinoma, (2) histological subtype: squamous cell, adenocarcinoma or an adenosquamous tumor, (3) exclusion of patients with radiological PA+ (CT scan/MRI), (4) pelvic external radiation therapy of 45 Gy with concomitant chemotherapy (cisplatin 40 mg/m2/week) + utero-vaginal brachytherapy, and (5) completion surgery after the end of PCRT including at least a para-aortic lymphadenectomy. RESULTS: Seventy-three patients (16 stage IB2, 57 stage II) treated between 1998 and 2004 fulfilled all the inclusion criteria. PA+ after PCRT were observed in 13 patients (18%) with a median of five (range, 2-22) positive nodes. Overall and disease-free survival at 24 months in patients with PA+ was 40% and 17%. Only two patients with PA+ are currently alive and in remission. CONCLUSIONS: The rate of PA+ remains high after PCRT in patients treated for stage IB2/II cervical carcinoma. Furthermore, the survival rate of patients with PA+ is very low. These important results suggest that detection of PA + at the time of completion surgery (after PCRT) is not beneficial for improving survival.

Endometrial disorders in patients with peritoneal serous papillary carcinoma.

BACKGROUND: The purpose of this study was to evaluate the incidence rate of endometrial disease, particularly endometrial carcinoma, in patients with primary peritoneal serous papillary carcinoma (PSPC). METHODS: Retrospective review of clinical and histological data from 32 women undergoing surgery (with hysterectomy) for stage III or IV PSPC. RESULTS: Six patients underwent primary debulking surgery and 26 underwent interval debulking surgery after 3 or 4 courses of platinum-based chemotherapy. Six patients (18%) had endometrial disease (hyperplasia in four). Two patients had endometrioid adenocarcinoma of the uterine body (stage IA grade 1 in one case, and stage IB grade 1 in the other) associated with the PSPC. CONCLUSIONS: Endometrial carcinoma of the uterine body may be associated with PSPC (6% cases in the present series). This result suggests that systematic hysterectomy should be performed at the time of debulking surgery in PSPC, even in the absence of peritoneal spread within pelvic cavity.

Growing teratoma syndrome after ovarian germ cell tumors.

OBJECTIVE: To analyze a series of occurrences of growing teratoma syndrome after ovarian germ cell tumors. METHODS: We analyzed a database containing 103 patients affected by pure or mixed ovarian immature teratoma. RESULTS: We report 12 patients fulfilling growing teratoma syndrome criteria (incidence 12%). The median interval between the diagnosis of ovarian immature teratoma and growing teratoma syndrome was 9 months (range 4-55). Growing teratoma syndrome was revealed by radiological examinations in nine cases (75%). In all cases but one, growing teratoma syndrome occurred in the site involved by the primary tumor. The peritoneum was the first site involved (10 cases, 83%). A complete surgical resection of the growing teratoma syndrome was done in eight cases. The median follow-up was 144 months. Four patients presented a late growing teratoma syndrome recurrence after treatment (second event), more than 5 years after the initial diagnosis, and 14 years later for one patient. All patients but one (lost to follow-up) were still alive at the end of the study. CONCLUSION: The treatment of growing teratoma syndrome consists of the surgical resection of the tumor, as completely as possible. Because of the possibility of very late recurrence of growing teratoma syndrome, a prolonged follow-up of patients treated for ovarian immature teratoma is mandatory.

[Medical treatment of metastatic or recurrent cancer of the cervix]. / Traitement médical des cancers du col utérin métastatiques ou récidivants.

Cervical cancer is the most frequent gynaecological cancer worldwide. Incidence is decreasing in industrialized countries but remains high in poorest countries. In metastatic or recurrent disease, the treatment is more often palliative. Chemotherapy yields some efficiency in non-irradiated fields but the benefit should be balanced with the treatment toxicities. In this setting, cisplatin is considered as the drug of reference, but responses rates are poor. So far, combined chemotherapy has not been shown better than cisplatin alone. Recently, results for cisplatin associated with topotecan appear to be promising while used for treatment in metastatic or recurrent disease. However, the bad prognosis of this illness leads to keep on looking for better treatments. Targeted therapeutics and immunotherapy against human papilloma virus could bear significant progress for treatment of cervical cancer.

Conservative treatment in epithelial ovarian cancer: results of a multicentre study of the GCCLCC (Groupe des Chirurgiens de Centre de Lutte Contre le Cancer) and SFOG (Société Francaise d'Oncologie Gynécologique).

BACKGROUND: Results of conservative management of epithelial ovarian cancer (EOC) remain controversial in the literature. The aim of this study was to assess the clinical outcomes and fertility following fertility-sparing surgical management of EOC in a retrospective multicentre study. METHODS: A multicentre retrospective study was performed by members of two French groups. Six inclusion criteria were defined: (i) Histological review by the same pathologist; (ii) age < or =40 years; (iii) conservative management; (iv) complete peritoneal staging; (v) delivery of a platinum-based chemotherapy in stage > or = IC; and (vi) follow-up >1 year. RESULTS: Thirty-four patients fulfilled the inclusion criteria: 30 had stage IA disease; three had stage IC and one had stage IIA. Eleven patients had recurrence: 10 patients had invasive disease and one had borderline recurrence. Among 10 patients with invasive recurrence, initial stage and grade were: stage IA G1, n = 1; stage IA G2, n = 4; stage IA G3, n = 1; and stage> or = IC, n = 4. All patients with stage > IA had recurrence. Ten pregnancies were observed in nine patients. CONCLUSION: Conservative surgery for patients with EOC could be considered in young patients with stage IA G1 disease. This procedure should not be performed in patients with FIGO stage > IA.

Results of hysterectomy in patients with bulky residual disease at the end of chemoradiotherapy for stage IB2/II cervical carcinoma.

BACKGROUND: We assessed the clinical outcome after hysterectomy in patients with bulky residual disease after chemoradiotherapy for stage IB2/II cervical carcinoma. METHODS: Subjects were 10 patients who had bulky (>2 cm) residual disease in the cervix after external radiotherapy (45 Gy) combined with concomitant chemotherapy (cisplatin 40 mg/m2/week) and uterovaginal brachytherapy (15 Gy). RESULTS: Extrafascial hysterectomy was performed in three patients, type II radical hysterectomy was performed in six patients, and pelvic exenteration was performed in one patient. Pelvic lymphadenectomy was performed in eight patients, and para-aortic lymphadenectomy was performed in eight. Five patients had nodal involvement (pelvic nodes in four and para-aortic nodes in four), and six had lymphovascular space involvement. Surgical margins were free in nine patients. Seven patients developed grade 2 (n = 3) and/or grade 3 (n = 4) complications. The median duration of follow-up after surgery was 22 months (range, 1-37 months). With follow-up available in nine patients, seven relapsed, and only two remained disease free. CONCLUSIONS: This series confirms the high rate of nodal spread in patients with bulky residual cervical disease after chemoradiotherapy. Furthermore, patients who underwent hysterectomy had a high complication rate. Only two patients are alive and disease free. The results of surgery are disappointing; surgery does not seem to improve the survival of these patients.

Results after laparoscopic management of serous borderline tumor of the ovary with peritoneal implants.

OBJECTIVE: The aim of this study is to assess the clinical outcomes of laparoscopic treatment of borderline ovarian tumor (BOT) with peritoneal implants. METHODS: Retrospective analysis of patients treated initially and/or for recurrent disease using a laparoscopic approach for a stage II or stage III BOT between January 2001 and January 2004. RESULTS: Nine patients underwent a laparoscopic pure treatment of stage II/III serous borderline tumor. Three of them had a previous history of BOT. Three patients had a stage II and 6 a stage III disease. A conservative management was performed in 7 patients. Laparoscopic treatment of peritoneal implants included: omentectomy (or omental biopsies) in 4 patients and/or large peritoneal resection in 5 patients (pelvic peritoneum in all patients associated with peritonectomies of paracolic gutters in 2 and of the peritoneum of the right diaphragmatic peritoneum in 3). Implants were nonivasive in 8 patients. Each of implant had a size <5 mm. Four patients recurred, 3 of them had a borderline ovarian recurrence after conservative management. Two patients had peritoneal disease found during a second-look surgery (associated with ovarian recurrence in 1). Three spontaneous pregnancies were observed. All patients are alive without evidence of disease with a median time of follow-up of 35 months following the laparoscopic treatment. CONCLUSION: Our series suggests that laparoscopic treatment of patients with BOT associated with small size non-invasive implants is feasible and seem to be safe. The main indication of this management consists in young patients treated conservatively to preserve their fertility.

Lymph node spread in stage III or IV primary peritoneal serous papillary carcinoma.

BACKGROUND: The aim of this study was to determine the rates and topography of pelvic and para-aortic nodal involvement in patients with stage III or IV primary peritoneal serous papillary carcinoma (PSPC). METHODS: Retrospective review of 19 women who underwent a systematic bilateral pelvic and para-aortic lymphadenectomy. RESULTS: The overall frequency of lymph node involvement was 63% (12/19). Eighteen patients underwent complete resection of peritoneal disease. Only 4 patients underwent this procedure as part of their initial surgery (before chemotherapy). The frequency of pelvic and para-aortic metastases was 58% (11/19) and 58% (11/19), respectively. When para-aortic nodes were involved, the left para-aortic chain above the level of the inferior mesenteric artery was the site most frequently involved (72%). The event-free survival of the 18 patients without macroscopic disease at the end of debulking surgery was significantly correlated with the nodal status. None of the patients with positive nodes developed recurrent disease in abdominal nodes. CONCLUSIONS: The rate of nodal involvement in patients with PSPC is high. The topography of nodal spread is similar to that of ovarian cancer. Lymphadenectomy has a prognostic value.

Advances in the surgical management of invasive cervical cancer.

PURPOSE OF REVIEW: Cervical cancer is the second most frequent cancer in women in the world. Surgery plays a major role, particularly in patients with early-stage disease. This review focuses on the evaluation of important papers published since January 2003 on the management of invasive cervical cancer. RECENT FINDINGS: Patients are classified as having early-stage (stage IB1) or advanced-stage (stage IB2 or greater) disease. Several papers are devoted to the evaluation of prognostic factors in patients with early-stage disease and negative nodes. Several recurrences after radical trachelectomy have been reported that remind us that strict selection criteria are mandatory for conservative management. The development of sentinel node and laparoscopic procedures has gained momentum. For patients with advanced-stage disease, the place of staging procedures in para-aortic areas or pelvic surgery after chemoradiation therapy continues to be debated and is currently being investigated in randomized studies. Several papers also continue to debate surgical treatment modalities for recurrent disease (the place of laparoscopy and reconstructive surgery). SUMMARY: Several interesting papers have been published since 2003 about the surgical treatment of cervical cancer. Laparoscopic surgery and the sentinel node procedure have developed considerably, particularly for the surgical management of early-stage disease. The results of ongoing studies are awaited to determine the value of pelvic surgery (after neoadjuvant treatment) in patients with advanced-stage disease.

Anatomy of pelvic and para-aortic nodal spread in patients with primary fallopian tube carcinoma.

BACKGROUND: To describe characteristics of patients with nodal spread and the anatomy of pelvic and para-aortic node involvement in primary fallopian tube carcinoma. STUDY DESIGN: Between 1985 and 2003, 19 women with primary fallopian tube carcinoma underwent systematic bilateral pelvic and para-aortic lymphadenectomy up to the level of the left renal vein. Initial lymphadenectomy (without chemotherapy) was performed in 6 patients and in 13 patients lymphadenectomies were performed after chemotherapy at the time of second-look operation. RESULTS: Nine patients had nodal involvement: four in the pelvic area and eight in the para-aortic nodes. Two, one, and six patients had stages I, II, or III disease, respectively. When para-aortic nodes were involved, the left para-aortic chain above the level of the inferior mesenteric artery was the site most frequently involved (six patients). CONCLUSIONS: In patients with primary tubal carcinoma, the left para-aortic chain above the level of the inferior mesenteric artery is the most frequently involved. Lymphadenectomy should involve all pelvic and para-aortic chains up to the level of the left renal vein, even in patients with stage I disease.

A need for laparoscopic evaluation of patients with endometrial carcinoma selected for conservative treatment.

BACKGROUND: The aim of this paper was to report two cases of extrauterine disease in patients with early stage endometrial cancer (EC) who desired fertility-sparing management. CASES: Two patients presenting an apparent early stage EC and desiring conservative management. The two patients, aged 35 and 36 years old, had a grade 1 and grade 2 EC diagnosed after curettage or hysteroscopic resection of a polyp. Ultrasound (US) imaging was normal (ovary). Once informed about the risk of recurrence, both patients opted for conventional therapy (hysterectomy with bilateral salpingo-oophorectomy). A small ovarian carcinoma was found in one patient and isolated positive peritoneal cytology in the other. CONCLUSIONS: These cases seem to suggest that laparoscopic evaluation including adnexal exploration and peritoneal cytology (and possibly pelvic lymphadenectomy) should be performed in patients with early stage EC selected for conservative management to confirm the absence of extrauterine disease.

[Concomitant chemoradiation in patients with cervix cancer]. / Associations chimioradiothérapie chez les patientes atteintes d'un carcinome du col utérin.

Cervical cancer is the 2nd most common cancer among women, behind breast cancer. Concomitant chemoradiation has been assessed in more than 15 randomised clinical trials. A meta-analysis for overall survival showed a statistically significant difference in favour of chemoradiotherapy: relative risk (RR) = 1.20, 95% confidence interval (CI) = 1.14-1.26, p < 0.001, p hetero = 0.21). Disease-free survival was also statistically significantly higher in favour of chemoradiotherapy: RR = 1.26, 95%CI = 1.17-1.35, p < 0.001). The benefit was more pronounced in trials including a higher proportion of stage I and II patients. Concomitant chemoradiotherapy showed a significant benefit for both local control and distant metastasis. Gastrointestinal and haematological toxicities were significantly more frequent in the chemoradiotherapy group. Details of late toxicity were sparse and therefore it was not possible to conclude on an increase of late complication rate with concomitant chemoradiotherapy. The inclusion criteria were not the same in all the trials, resulting in populations with varying distributions in disease stages. In addition, the treatment schemas for both radiotherapy and chemotherapy used in these trials were different. These results were obtained with chemotherapy based on various molecules, including cisplatin, either alone or with other cytotoxic drugs, such as 5-fluorouracil. For a similar level of benefit, the combination of cisplatin, 5-fluorouracil and hydroxyurea was more toxic than cisplatin alone in one trial in which the two protocols were compared. Future randomised trials should also aim to establish optimal chemotherapy regimens for combination with radiotherapy.

Port-site implantation after laparoscopic treatment of borderline ovarian tumors.

BACKGROUND: The aim of this article is to report 3 cases of port-site implantation after laparoscopic treatment of a borderline ovarian tumor. CASES: Three patients underwent a laparoscopic procedure for a serous (2 patients) or mucinous (1 patient) borderline ovarian tumor. In 2 patients, the port-site implantation was discovered during a later surgical procedure, and one was discovered clinically 11 months after the initial laparoscopic oophorectomy. Surgical resection of the port-site was the only treatment in all cases. These women are currently alive and disease-free 11, 23, and 51 months after the treatment of the scar metastasis. CONCLUSIONS: These results suggest that, unlike port-site metastasis in other gynecologic malignancies, the prognosis in patients with a port-site implantation after laparoscopic management of borderline ovarian tumor is excellent. The treatment of this complication is surgical resection.

Contralateral groin recurrence in patients with stage I Bartholin's gland squamous cell carcinoma and negative ipsilateral nodes: report on two cases and implications for lymphadenectomy.

BACKGROUND: Modalities of inguinal lymphadenectomy in patients with early stage Bartholin's gland squamous cell carcinoma (BGC) remain discussed. The aim of this paper is to report 2 patients with stage 1 BGC and negative ipsilateral groin nodes who developed a contralateral groin recurrence. CASES: Two patients treated for BGC and undergoing an ipsilateral groin nodes dissection (with absence of nodal involvement) presented contralateral groin recurrence. These recurrences were observed 14 and 3 months after the initial treatment in the first and second case. In the first case, the nodal recurrence was associated with a local vaginal recurrence. CONCLUSIONS: These 2 cases suggest that << cross >> groin nodal involvement can occur, even in patients with early stage BGC. Bilateral groin dissection should be performed in patients with BGC.

Preservation of pregnancy in a patient with a stage IIIB ovarian epithelial carcinoma diagnosed at 22 weeks of gestation and treated with initial chemotherapy: case report and literature review.

BACKGROUND: To report a case of successful management of a FIGO stage III endometrioid carcinoma of the ovary diagnosed during pregnancy at 22 weeks of gestation and treated with initial chemotherapy while preserving the pregnancy. CASE: The patient underwent a planned cesarean section at 34 weeks after two courses of carboplatin. She delivered a healthy baby. At the same time, a radical hysterectomy, omentectomy, pelvic and paraaortic lymphadenectomies and peritonectomies were carried out. The surgical resection was complete (no macroscopic residual disease). During histologic examination, traces of persistent disease were found. The patient underwent seven postoperative courses of chemotherapy (carboplatin + paclitaxel regimen) after radical surgery. After 18 months of follow-up posttreatment, the patient remains in complete remission and the child's development is normal. CONCLUSION: Chemotherapy during pregnancy with preservation of the fetus could be considered and should be discussed in case of epithelial ovarian cancer (EOC) diagnosed during the second trimester of the pregnancy.

Impact of surgical staging in patients with macroscopic "stage I" ovarian borderline tumours: analysis of a continuous series of 101 cases.

The aim of this study was to assess the patient's clinical outcome following complete or incomplete surgical staging in cases treated for an early stage low-malignant-potential ovarian tumour (LMPOT). One-hundred and one patients treated between 1965 and 1998 for a early stage I LMPOT were reviewed according to whether the initial surgical staging was complete (Group 1/defined by peritoneal cytology + peritoneal biopsies + infracolic omentectomy) or incomplete (Group 2/omission of at least one of the peritoneal staging procedures described above). Complete and incomplete surgical stagings were carried out in 48 (48%) and 53 (52%) patients, respectively. Four (8%) LMPOT recurrences were observed in Group 2, all following conservative management, but there were no recurrences in Group 1. No relapses with invasive carcinoma or peritoneal disease and no tumour-related deaths were observed. The absence of complete peritoneal staging in patients with an apparent "stage I" LMPOT increased the recurrence rate. However, this surgical restaging (in cases of incomplete initial surgery) does not modify the survival of patients with apparent "stage I" LMPOT misdiagnosed during the initial surgery. This procedure could probably be omitted: (1) if the peritoneum is clearly reported as "normal" during the initial surgery; (2) in the absence of a micropapillary pattern; and (3) if the patient agrees to be carefully followed-up.

Outcomes after combined therapy including surgical resection in patients with epithelial ovarian cancer recurrence(s) exclusively in lymph nodes.

BACKGROUND: The aim was to study the prognosis for and survival of patients treated with combined therapy (including surgical resection) for nodal recurrences from epithelial ovarian cancer (EOC). METHODS: This was a retrospective study of a group of 12 patients with a recurrence from EOC, a priori, exclusively located in lymph node(s). All patients underwent surgical resection of nodal metastases, followed by adjuvant therapy. RESULTS: The median age of patients was 51 (range, 42-71) years. The initial disease stages were as follows: stage IA, n = 5; stage IIA, n = 1; and stage IIIC, n = 6. The median interval between the end of initial treatment and the nodal relapse was 21 (range, 6-72) months. The recurrence was located in the abdominal nodes in 10 patients (pelvic and/or para-aortic area) and was extra-pelvic in one patient, and the last patient had concomitant para-aortic and supraclavicular nodal involvement. Ten patients received postoperative chemotherapy and two had radiation therapy (one patient received both treatments). Eight patients relapsed and four did not. To date, three patients have died of the disease, three are alive with persistent disease, and six are alive and disease-free (including two patients who were treated by surgical resection after relapses twice in abdominal nodes). Five-year overall survival from the time of treatment of recurrent disease is 71% (confidence interval, 41%-90%). CONCLUSIONS: The prognosis of patients with an a priori isolated nodal recurrence from EOC was good in this group of treated with surgical resection followed by chemoradiation or radiation therapy. This finding argues in favor of proposing surgical resection in such patients.