Radical vaginal trachelectomy: long-term oncologic and fertility outcomes in patients with early cervical cancer.

OBJECTIVE: Radical vaginal trachelectomy is a fertility-preserving treatment for patients with early cervical cancer. Despite encouraging oncologic and fertility outcomes, large studies on radical vaginal trachelectomy are lacking. METHOD: Demographic, histological, fertility, and follow-up data of consecutive patients who underwent radical vaginal trachelectomy between March 1995 and August 2021 were prospectively recorded and retrospectively analyzed. RESULTS: A total of 471 patients of median age 33 years (range 21-44) were included. 83% (n=390) were nulliparous women. Indications were International Federation of Gynecology and Oncology (FIGO, 2009) stages IA1 with lymphvascular space involvement (LVSI) in 43 (9%) patients, IA1 multifocal in 8 (2%), IA2 in 92 (20%), IB1 in 321 (68%), and IB2/IIA in 7 (1%) patients, respectively. LVSI was detected in 31% (n=146). Lymph node staging was performed in 151 patients (32%) by the sentinel node technique with a median of 7 (range 2-14) lymph nodes and in 320 (68%) by systematic lymphadenectomy with a median of 19 (range 10-59) lymph nodes harvested. Residual tumor was histologically confirmed in 29% (n=136). In total, 270 patients (62%) were seeking pregnancy of which 196 (73%) succeeded. There were 205 live births with a median fetal weight of 2345 g (range 680-4010 g). Pre-term delivery occurred in 94 pregnancies (46%). After a median follow-up of 159 months (range 2-312), recurrences were detected in 16 patients (3.4%) of which 43% occurred later than 5 years after radical vaginal trachelectomy. Ten patients (2.1%) died of disease (five more than 5 years after radical vaginal trachelectomy). Overall survival, disease-free survival, and cancer-specific survival were 97.5%, 96.2%, and 97.9%, respectively. CONCLUSION: Our study confirms oncologic safety of radical vaginal trachelectomy associated with a high chance for childbearing. High rate of pre-term delivery may be due to cervical volume loss. Our long-term oncologic data can serve as a benchmark for future modifications of fertility-sparing surgery.

Oncologic and Fertility Outcomes After Simple Trachelectomy in Women With Early Cervical Cancer.

STUDY OBJECTIVE: This study aimed to present our case series of patients with early-stage cervical cancer undergoing simple trachelectomy (ST). Currently, radical trachelectomy is considered the most appropriate fertility-preserving procedure for the treatment of early-stage cervical cancer. However, there is increasing debate on the appropriate radicality of the surgery to preserve oncologic safety. DESIGN: Descriptive retrospective analysis of patient records and evaluation of questionnaires. SETTING: 2 gynecologic oncologic centers, surgeries performed by one surgical team. PATIENTS: 36 women with early-stage cervical cancer undergoing ST. INTERVENTIONS: Laparoscopic assisted simple vaginal trachelectomy. MEASUREMENTS: Demographic, histologic, fertility, and follow-up data of all patients who underwent ST between April 2007 and July 2021 were prospectively recorded and retrospectively analyzed. MAIN RESULTS: A total of 36 women (mean age: 28 years) underwent ST of whom 81% were nulliparous. Indications for ST were multifocal International Federation of Gynecology and Obstetrics stage IA1 (n = 30), stage IA1 L1 (n = 1), stage IA2 (n = 2), and stage IB1 (n = 3). Mandatory staging procedure was laparoscopic pelvic lymphadenectomy, including bilateral sentinel biopsy in 92% of the cases and systematic in 8%. Residual tumor was histologically confirmed in 8 specimens (22%); 18 women (50%) were seeking parenthood, and 13 succeeded (72%). There were 16 live births, all on term, with a median fetal weight of 3110 grams (2330-4420). One patient had a medical abortion owing to fetal congenital malformation. One pregnancy is ongoing. After a median follow-up of 91.5 months (9-174), all women are alive with no evidence of disease. CONCLUSION: ST represents a de-escalation compared with radical trachelectomy and provides excellent oncologic results with an outstanding fertility rate and obstetric outcome for patients with early cervical cancer. However, clear indications for this tailored fertility-preserving surgery have to be defined in well-designed trials.

HE4 as a serum biomarker for the diagnosis of pelvic masses: a prospective, multicenter study in 965 patients.

BACKGROUND: To evaluate the diagnostic value of adding human epididymis protein 4 (HE4), cancer antigen 125 (CA125) and risk of malignancy algorithm (ROMA) to ultrasound for detecting ovarian cancer in patients with a pelvic mass. METHODS: This was a prospective, observational, multicenter study. Patients aged > 18 years who were scheduled to undergo surgery for a suspicious pelvic mass had CA125 and HE4 levels measured prior to surgery, in addition to a routine transvaginal ultrasound scan. The diagnostic performance of CA125, HE4 and ROMA for distinguishing between benign and malignant adnexal masses was assessed using receiver operating characteristic (ROC) analysis and the corresponding area under the curve (AUC). RESULTS: Of 965 evaluable patients, 804 were diagnosed with benign tumors and 161 were diagnosed with ovarian cancer. In late-stage ovarian cancer, CA125, HE4 and ROMA all had an excellent diagnostic performance (AUC > 0.92), whereas in stage I and II, diagnostic performance of all three biomarkers was less adequate (AUC < 0.77). In the differential diagnosis of ovarian cancer and endometriosis, ROMA and HE4 performed better than CA125 with 99 and 98.1% versus 75.0% sensitivity, respectively, at 75.4% specificity. CONCLUSIONS: ROMA and HE4 could be valuable biomarkers to help with the diagnosis of ovarian cancer in premenopausal patients in order to differentiate from endometriosis, whereas CA125 may be more adequate for postmenopausal patients.

Patients' subjective assessment as a decisive predictor of malignancy in pelvic masses: results of a multicentric, prospective pelvic mass study.

OBJECTIVE: The prognosis for ovarian cancer patients remains poor. A key to maximizing survival rates is early detection and treatment. This requires an accurate prediction of malignancy. Our study seeks to improve the accuracy of prediction by focusing on early subjective assessment of malignancy. We therefore investigated the assessment of patients themselves in comparison to the assessment of physicians. METHODS: One thousand three hundred and thirty patients participated in a prospective and multicenter study in six hospitals in Berlin. Using univariate analysis and multivariate logistic regression models, we measured the accuracy of the early subjective assessment in comparison to the final histological outcome. Moreover, we investigated factors related to the assessment of patients and physicians. RESULTS: The patients' assessment of malignancy is remarkably accurate. With a positive predictive value of 58%, the majority of patients correctly assessed a pelvic mass as malignant. With more information available, physicians achieved only a slightly more accurate prediction of 63%. CONCLUSIONS: For the first time, our study considered subjective factors in the diagnostic process of pelvic masses. This paper demonstrates that the patients' personal assessment should be taken seriously as it can provide a significant contribution to earlier diagnosis and thus improved therapy and overall prognosis.

Laparoscopic temporary clipping of uterine artery during laparoscopic myomectomy.

PURPOSE: Our aim is to study the feasibility and effect of bilateral laparoscopic temporary occlusion of uterine arteries by special vascular clamps on blood loss during laparoscopic myomectomy. METHODS: Of 166 women with symptomatic uterine myomas necessitating surgical intervention who wished to retain their uteri, 80 underwent laparoscopic uterine artery clipping and myomectomy (experimental group) and 86 received laparoscopic myomectomy only (control group). Main outcome measures were operating time, number and weight of leiomyomas, blood loss, Doppler examination of the uterine arteries and complications of procedure. RESULTS: In the experimental group the median hemoglobin drop measured on day 3 postoperatively was 1.2 g/dl. In the control group the mean hemoglobin drop measured on day 3 postoperatively was 1.45 g/dl. The time needed to put the clips in place (the time from the opening of the retroperitoneum and the positioning of the clips) varied between 6 and 40 min. No patient required blood transfusion. There were no conspicuous complications. CONCLUSION: The use of the clips has proved to be statistically effective in reducing hemoglobin loss during laparoscopic myomectomy.

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.

Addressing concerns about cisplatin application during pregnancy.

INTRODUCTION: Cervical cancer in second trimester of pregnancy is an oncologic challenge. Cisplatin is recommended to prevent cancer progression. This is a series correlating in vivo cisplatin concentration in the fetomaternal compartment and in breast milk with child development. METHODS: Eight consecutive patients with cervical cancer diagnosed during the second trimester underwent conization/biopsy and/or pelvic laparoscopic lymphadenectomy (LAE). Delay of pregnancy in combination with neoadjuvant monochemotherapy was performed. After 2-4 cycles of cisplatin monochemotherapy cesarean section followed by radical hysterectomy was performed above 31 weeks of gestation. Synchronous samples from maternal blood, umbilical cord blood, and amniotic fluid were taken and analyzed. A probe of breast milk was taken from three patients. Pediatric aftercare was done every three months postpartum. RESULTS: Laparoscopic LAE was uncomplicated in all patients. In seven out of eight patients lymph nodes were tumor free. Nine healthy babies were delivered. Pediatric follow-up showed normal development. Cisplatin concentrations in the umbilical cord and amniotic fluid were 31-65% and 13-42% of the amount in maternal blood, respectively. In breast milk, cisplatin was detectable in 1-10% of maternal blood concentration. CONCLUSION: Knowledge of significant lower cisplatin concentrations in fetal compartment and normal child growth provides additional security to apply cisplatin in pregnancy. Breastfeeding cannot be recommended.

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.

Vaginal-assisted laparoscopic radical hysterectomy: rationale, technique, results.

OBJECTIVE: Total laparoscopic radical hysterectomy (TLRH) makes it difficult to resect adequate vaginal cuff according to tumor size and to avoid tumor spread after opening the vagina. Laparoscopic-assisted radical vaginal hysterectomy (LARVH) is associated with higher risk for urologic complications. METHODS: The vaginal-assisted laparoscopic radical hysterectomy (VALRH) technique comprises 3 steps: (1) comprehensive laparoscopic staging, (2) creation of a tumoradapted vaginal cuff, and (3) laparoscopic transsection of parametria. We retrospectively analyzed data of 122 patients who underwent VALRH for early stage cervical cancer (n=110) or stage II endometrial cancer (n=12) between January 2007 and December 2009 at Charité University Berlin. RESULTS: All patients underwent VALRH without conversion. Mean operating time was 300 minutes, and mean blood loss was 123cc. On average, 36 lymph nodes were harvested. Intra- and postoperative complication rates were 0% and 13.1%, respectively. Resection was in sound margins in all patients. After median follow-up of 19 months, disease-free survival and overall survival for all 110 cervical cancer patients was 94% and 98%, and for the subgroup of patients (n=90) with tumors ≤pT1b1 N0 V0 L0/1 R0, 97% and 98%, respectively. CONCLUSION: VALRH is a valid alternative to abdominal radical hysterectomy and LARVH in patients with earlystage cervical cancer and endometrial cancer stage II with minimal intraoperative complications and identical oncologic outcomes.

Cisplatin application in pregnancy: first in vivo analysis of 7 patients.

Cervical cancer in pregnancy is an oncologic challenge. Empirical cisplatin is recommended to prevent cancer progression until fetal maturity. Seven patients with cervical cancer in the second trimester decided to delay delivery together with neoadjuvant chemotherapy. After 2-4 cycles, caesarean section and radical hysterectomy were performed above 32 weeks of gestation. Synchronous samples from maternal blood, umbilical cord blood and amniotic fluid were taken. All patients delivered healthy babies. Cisplatin concentrations in umbilical cord and amniotic fluid were 31-65 and 13-42% of the maternal blood, respectively. This is the first series on in vivo cisplatin concentration in the fetomaternal compartment.

Indications for primary and secondary exenterations in patients with cervical cancer.

OBJECTIVE: Fifty years after the introduction of exenterative surgery in gynecologic oncology, the indication for primary and secondary exenteration is controversially discussed in cervical cancer patients. In addition, the term "palliative exenteration" is not precisely defined. We evaluate the role of primary exenteration in patients with stage IVA cervical cancer and the role of secondary palliative exenteration. METHODS: The study retrospectively analyzed surgical and oncologic data of 55 patients who underwent exenterative surgery in the Department of Gynecology at the University of Jena between February 1998 and January 2004. Primary surgery was performed in 20 patients with laparoscopically confirmed stage IVA cervical cancer, while 35 patients with recurrent cervical cancer underwent secondary exenteration. Fifty-one had total, 3 posterior and 1 anterior exenteration. Survival was analyzed in relation to the patient's age, indication (primary versus secondary, curative versus palliative), previous therapy (operation, radiation, chemotherapy, radiochemotherapy), histology, resection margins, pelvic nodal involvement, time interval from primary therapy to recurrence, type of exenteration and adjuvant therapy. Early and late postoperative complications as well as perioperative mortality were reviewed. RESULTS: The overall cumulative survival of all patients after exenteration was 36.8% at 5 years with 52.5% in the primary group and 26.7% in the recurrent one (p=0.0472). Complications were noted in 56.9% of patients, most commonly fistulas or gastrointestinal complications. Operative mortality was 5.5%. Survival correlated significantly with the time interval between primary treatment and recurrence (within 1-2 years 16.8% five-year survival, 2-5 years 28%, >5 years 83.2%, p=0.0105) as well as with curative or palliative intention (2-year survival rate of 60% in patients with curative intent, 10.5% in those with palliative intent, p=0.0001) and with tumor-free resection margins (2-year survival of 10.2% for positive margins, 5-year survival of 55.2% for negatives ones, p=0.0057). The age, the type of exenteration, the histologic type and the metastatic spread to pelvic lymph nodes had no significant influence on long-term survival. CONCLUSION: In patients with histopathologically confirmed stage IVA cervical cancer primary, exenteration is a valid alternative to primary chemoradiation. In patients with persistent or recurrent tumor limited to the pelvis, secondary exenteration should be offered in the absence of other therapeutic options. Palliative and curative attempts can best be differentiated by the resection margin status.