Dorothee Speiser

Fertility outcome after radical vaginal trachelectomy: a prospective study of 212 patients.

Objective For treatment in patients with early-stage cervical cancer, radical vaginal trachelectomy (RVT) as a fertility-preserving surgery can be put on a par with radical hysterectomy as to oncologic safety. Our aim was to investigate the fertility concerns and outcome. Methods Prospective collection of fertility data of patients treated with RVT. The data were collected on personal communication, by telephone, or e-mail correspondence. Descriptive statistical analysis was performed. Results Between March 2005 and April 2010, 212 patients were followed up after RVT. Only 76 patients (35.9%) were seeking parenthood currently. Sixty pregnancies occurred in 50 women. Five patients (8.3%) had first-trimester miscarriage, 3 had second-trimester miscarriage (5.0%), 2 patients decided for pregnancy termination (3.3%), and 1 patient (1.7%) had an ectopic pregnancy. Three women (5.0%) delivered prematurely before 28th weeks of gestation, 15 (25.0%) delivered between 28 and 36 weeks, and 27 women (45.0%) reached full term. Four pregnancies are ongoing. Conclusions Preservation of childbearing function is a great advantage for patients with early-stage cervical cancer. Many patients do not seek parenthood immediately. We see no impairment of fertility and have solid data on pregnancy outcome. Premature labor is the main problem in pregnancy after RVT.

Radical vaginal trachelectomy (RVT) combined with laparoscopic lymphadenectomy: Prospective study of 225 patients with early-stage cervical cancer

Objective: The aim of the study was to prove the surgical and oncological safety of radical vaginal trachelectomy (RVT) and laparoscopic lymphadenectomy for patients with early-stage cervical cancer who are seeking parenthood. Methods: A database of 225 patients with early-stage cervical cancer and intention to treat by RVT after laparoscopic lymphadenectomy was prospectively maintained. A total of 212 patients were treated according to the protocol. The procedure was preformed in a standardized manner, and life table analysis was applied. Results: In the cohort of patients treated according to protocol, 8 recurrences occurred and 4 patients died from recurrence. The median follow-up time was 37 months (range, 0-171 months). The 5-year recurrence-free and overall survival was 94.4% and 97.4%, respectively. Perioperative and short-term postoperative complications were rare (2.8% and 7.5%, respectively). No severe long-term complications occurred. Conclusions: Radical vaginal trachelectomy combined with laparoscopic lymphadenectomy is a safe method for treatment of patients with early-stage cervical cancer who are seeking parenthood.

Prevalence of BRCA1/2 germline mutations in 21 401 families with breast and ovarian cancer

Purpose To characterise the prevalence of pathogenic germline mutations in BRCA1 and BRCA2 in families with breast cancer (BC) and ovarian cancer (OC) history. Patients and methods Data from 21 401 families were gathered between 1996 and 2014 in a clinical setting in the German Consortium for Hereditary Breast and Ovarian Cancer, comprising full pedigrees with cancer status of all individual members at the time of first counselling, and BRCA1/2 mutation status of the index patient. Results The overall BRCA1/2 mutation prevalence was 24.0% (95% CI 23.4% to 24.6%). Highest mutation frequencies were observed in families with at least two OCs (41.9%, 95% CI 36.1% to 48.0%) and families with at least one breast and one OC (41.6%, 95% CI 40.3% to 43.0%), followed by male BC with at least one female BC or OC (35.8%; 95% CI 32.2% to 39.6%). In families with a single case of early BC (<36 years), mutations were found in 13.7% (95% CI 11.9% to 15.7%). Postmenopausal unilateral or bilateral BC did not increase the probability of mutation detection. Occurrence of premenopausal BC and OC in the same woman led to higher mutation frequencies compared with the occurrence of these two cancers in different individuals (49.0%; 95% CI 41.0% to 57.0% vs 31.5%; 95% CI 28.0% to 35.2%). Conclusions Our data provide guidance for healthcare professionals and decision-makers to identify individuals who should undergo genetic testing for hereditary breast and ovarian cancer. Moreover, it supports informed decision-making of counselees on the uptake of genetic testing.

Laparoscopic lymph node dissection should be performed before fertility preserving treatment of patients with cervical cancer

OBJECTIVE The aim of this study is to assess our results of treatment of women with stage I cervical cancer>2 cm in diameter seeking fertility preservation. Treatment consisted of Laparoscopic Pelvic and Paraaortic Lymphadenectomy (LPPLND), and when no nodal metastasis was detected, neoadjuvant chemotherapy (NACT) followed by radical vaginal trachelectomy (RVT). Patients with positive lymph nodes underwent primary chemoradiation. METHODS A cohort of women younger than 40 years of age with stage I disease>2 cm who underwent LPPLND and either NACT and RVT or chemoradiation. Oncological outcome was evaluated prospectively. RESULTS Eighteen women were eligible for this study. Twelve (67%) women were diagnosed with metastasis in one or more pelvic and/or paraaortic lymph nodes, and thus received primary chemoradiation. After a mean follow-up of 25.5 months, three out of these 12 women (25%) developed a recurrence. Six women (33%) underwent NACT and RVT. Three patients experienced complete response to NACT and three patients showed more than 50% tumor size reduction. After a mean follow-up of 30.6 months all six women are free of recurrence. One patient delivered a healthy infant. CONCLUSIONS Staging LPPLND allows separating patients in high or low recurrence risk groups. NACT and RVT seem to be safe for women with completely staged stage I cervical cancer>2 cm in diameter, whereas even after primary chemoradiation, patients with positive lymph nodes experienced recurrence. Therefore, selection of patients with stage I cervical carcinoma>2 cm, eligible for fertility preservation should include histopathologic evaluation of lymph node status before any further treatment.

Radical vaginal trachelectomy after laparoscopic staging and neoadjuvant chemotherapy in women with early-stage cervical cancer over 2 cm: oncologic, fertility, and neonatal outcome in a series of 20 patients.

Objectives The aim of the study was to assess oncologic and fertility outcome of treatment in patients with cervical cancer of more than 2 cm seeking parenthood. Methods The regimen consisted of laparoscopic lymphadenectomy as a staging procedure to confirm no lymph node metastases before neoadjuvant chemotherapy (NACT) consisting of 2 or 3 cycles of paclitaxel/ifosfamide/cisplatin followed by radical vaginal trachelectomy (RVT). Oncologic and fertility outcome was evaluated prospectively. Results Twenty women were enrolled up to now. The mean age was 32 years (range, 26–41 years), and mean tumor size was 3 cm (range, 2.1–5.0 cm). Lymphadenectomy was performed before NACT without complications. During NACT, hematologic toxicity grade 3 was observed in 2 of 20 patients, and renal toxicity grade 3 in 1 of 20 patients. Radical vaginal trachelectomy was performed in 18 women until now with 2 intraoperative complications (ureter injury and injury of internal iliac vein). There were no severe postoperative or long-term complications. Complete pathologic remission was found in 9 of 18 patients. In 2 of 18 patients, chemoradiation was recommended because of insufficient pathologic response in the RVT specimen. After a mean follow-up of 23 months (range, 1–88 months), 1 relapse was observed. After RVT, 7 women tried to conceive until now. Seven pregnancies occurred in 5 women. Four children were born, 2 of whom were premature (31 weeks 2 days and 33 weeks 4 days of gestation); 1 pregnancy is ongoing. Conclusions Laparoscopic lymphadenectomy followed by NACT and RVT in pN0 patients with cervical cancer of more than 2 cm seems to be an oncologically safe procedure with promising fertility outcomes.

Pattern of cancer recurrence in 320 patients after radical vaginal trachelectomy.

Objective The oncological outcome regarding disease-free survival and overall survival after radical vaginal trachelectomy (RVT) is the same as the rates after radical hysterectomy. We aim to analyze predictive and risk factors and death in patients with cervical cancer undergoing fertility preservation by laparoscopic lymphadenectomy and RVT. Methods Three hundred twenty patients with cervical cancer underwent RVT between March 1995 and February 2013. In our study, we examined recurrence rates analyzed by risk factors. We classified the presence of lymphovascular space invasion, depth of tumor infiltration, tumor size, and tumor grading as risk factors. The mean follow-up time was 48 months. Results Ten of the 320 patients had cancer recurrence. Recurrence appeared at a mean time of 26.1 months (3–108 months) after RVT. Five patients died within 8.8 months (4–15 months) after recurrence was diagnosed. Two of these 5 patients had distant metastasis at the time of recurrence. Five patients were treated successfully by surgery, and 4 patients were treated successfully by chemotherapy. The mean follow-up after the recurrence of these 5 patients is 76 months (6–120 months). None of the 10 patients with recurrences in our series showed significant high-risk factors. Conclusion There seems to be no pattern in the recurrence of cancer after RVT. It is strictly mandatory to follow up the patients closely every 3 months after RVT to diagnose recurrence at an early stage so therapeutic options such as chemoradiation are still available. Once distant metastasis occurs, prognosis is not good.

Validation of the Manchester scoring system for predicting BRCA1/2 mutations in 9,390 families suspected of having hereditary breast and ovarian cancer

The Manchester scoring system (MSS) allows the calculation of the probability for the presence of mutations in BRCA1 or BRCA2 genes in families suspected of having hereditary breast and ovarian cancer. In 9,390 families, we determined the predictive performance of the MSS without (MSS‐2004) and with (MSS‐2009) consideration of pathology parameters. Moreover, we validated a recalibrated version of the MSS‐2009 (MSS‐recal). Families were included in the registry of the German Consortium for Hereditary Breast and Ovarian Cancer, using defined clinical criteria. Receiver operating characteristics (ROC) analysis was used to determine the predictive performance. The recalibrated model was developed using logistic regression analysis and tested using an independent random validation sample. The area under the ROC curves regarding a mutation in any of the two BRCA genes was 0.77 (95%CI 0.75–0.79) for MSS‐2004, 0.80 (95%CI 0.78–0.82) for MSS‐2009, and 0.82 (95%CI 0.80–0.83) for MSS‐recal. Sensitivity at the 10% mutation probability cutoff was similar for all three models (MSS‐2004 92.2%, MSS‐2009 92.2%, and MSS‐recal 90.3%), but specificity of MSS‐recal (46.0%) was considerably higher than that of MSS‐2004 (25.4%) and MSS‐2009 (32.3%). In the MSS‐recal model, almost all predictors of the original MSS were significantly predictive. However, the score values of some predictors, for example, high grade triple negative breast cancers, differed considerably from the originally proposed score values. The original MSS performed well in our sample of high risk families. The use of pathological parameters increased the predictive performance significantly. Recalibration improved the specificity considerably without losing much sensitivity.

Radical vaginal trachelectomy: a fertility-preserving procedure in early cervical cancer in young women.

BACKGROUND Radical vaginal trachelectomy (RVT) is a fertility-preserving operation for young women who have cervical cancer in an early stage and want to have children. The demand for RVT is increasing, because more than 40% of all cases of cervical carcinoma affect women under the age of 44. Women are increasingly having their first child at later ages. METHODS We present the results of RVT in more than 300 patients whom we operated on, review pertinent literature retrieved by a selective PubMed search, and evaluate treatment recommendations. RESULTS The literature contains data on more than 1000 women treated with RVT and nearly 300 pregnancies after RVT. The 5-year recurrence and mortality rates are 2%-5% and 3%-6%, respectively. RVT is an oncologically safe treatment for women who want to have children. The main criteria for treatment with RVT are that the tumor should be no greater than 2 cm in diameter and that the lymph nodes should be histopathologically free of tumor tissue. The laparoscopic-vaginal technique is the best operative approach to assure a high rate of healing. Only one-third of all patients want to have children a short time after RVT. Their pregnancy rates resemble those of women in the general population. 50% of the children are born prematurely, mainly because of premature rupture of the membranes. Thus, pregnancies after RVT are considered high-risk pregnancies. CONCLUSION As many as 48% of women with early-stage cervical carcinoma meet the criteria for RVT. RVT is an oncologically safe method that enables women with early-stage cervical carcinoma to become pregnant and have children. Pregnancy after RVT is associated with an elevated risk of preterm birth and should be managed according to standardized procedures.

Prevalence of lymph nodes in the parametrium of radical vaginal trachelectomy (RVT) specimen.

OBJECTIVE In order to evaluate radicality in fertility preserving surgery in women with early invasive cervical cancer we analyzed the parametrium of specimens of patients treated by radical vaginal trachelectomy for the presence of lymph nodes. We tried to identify morphologic factors associated with the presence of parametrial lymph nodes. METHODS We analyzed surgical specimens of 112 patients who underwent radical trachelectomy between June 2004 and April 2009 at the Department of Gynecologic Oncology at Charité Campus Benjamin Franklin and Campus Mitte. All parametrial tissue was step sectioned and a total of 1878H&E stained histological sections were analyzed. RESULTS In 8 patients (7.1%) a total of 13 lymph nodes were detected. Five lymph nodes in four patients had been primarily detected by routine histological examination. In one of these patients (0.9%) a 2mm lymph node metastasis was found. Serial sectioning revealed additional seven lymph nodes in four patients. The thickness of parametrium correlated significantly with the presence of lymph nodes in the parametrium. CONCLUSION The presence of small lymph nodes in the parametrium of specimens of radical trachelectomy is low. In patients with early-stage cervical cancer, the incidence of metastasis is less than 1%. Preoperative assessment of the volume of the parametrium may indicate which patients need parametrial resection.

Neonatal outcome in infants of patients with radical vaginal trachelectomy

Abstract Objective: Radical vaginal trachelectomy (RVT) as a fertility-preserving surgery in patients with early-stage cervical cancer is proven to be oncologically safe. After RVT, pregnancy rates vary between 40% and 80%. Outcome of infants is complicated by a preterm delivery rate of 30–50%. We investigated pregnancy and neonatal outcome after RVT. Methods: A total of 154 patients with cervical cancer underwent RVT between March 1995 and February 2008. Desire to conceive, pregnancy data, and neonatal outcome were prospectively recorded. Infants’ data were pair-matched to data of a control group according to weeks of gestation. Bayley scales of infant development scores were recorded in the group of preterm-delivered infants. Results: Fifty-five women who underwent RVT gave birth to 58 children. Twenty-five (43%) pregnancies were complicated by preterm rupture of membranes. Thirty infants (52%) were born preterm, of with 17 (29%) were <32 gestational weeks (GW) and seven (12%) were <28 GW. There were significantly more premature rupture of membranes in pregnancies after RVT. Despite a higher occurrence of postnatal infections in newborns of mothers who underwent RVT, long-term outcomes are not affected negatively. Regarding overall morbidity, a trend to fewer postnatal complications, compared with the control group, was found. Conclusion: Postnatal morbidity in infants of women who underwent RVT, based on trend, is decreased compared with controls. Intense medical observation and treatment during pregnancy, birth, and neonatal period may explain this finding. Neonates in the RVT group have a non-significantly elevated risk for postnatal infections. They do not show an additional risk due to the maternal operation. Their long-term postnatal outcome is not affected negatively.