Reproductive outcomes after fertility-sparing surgery for cervical cancer - results of the multicenter FERTISS study.

INTRODUCTION: Fertility-sparing treatment (FST) for patients with cervical cancer intends to achieve oncologic outcomes comparable to those after radical treatment while maximizing reproductive outcomes, including the ability to conceive and minimizing the risk of prematurity. METHODOLOGY: International multicentre retrospective FERTISS study focused on patients treated with FST analysed timing of FST relative to pregnancy, conception attempts and methods, abortion rates, prophylactic procedures reducing the risk of severe prematurity, pregnancy duration, and delivery mode. RESULTS: Of the 733 patients treated at 44 centres in 13 countries, 49.7% attempted to conceive during median follow-up of 72 months and 22.6% (166/733) patients achieved a successful pregnancy. Success rate was significantly higher after non-radical surgery (63.2%; 122/193) compared to radical trachelectomy (25.7%; 44/171, p < 0.001). Available perinatological data shows that 89.5% (111/124) of the patients became pregnant naturally. There was no significant difference in the abortion rate in the first pregnancy nor delivery success rates between non-radical and radical procedures patients. Preterm delivery (<38 weeks gestation) occurred more frequently after radical than non-radical procedures (76.5% vs. 57.7%, p = 0.15). Almost all patients (97.3%; 73/75) who underwent regular ultrasound cervicometry in pregnancy with subsequent prophylactic procedures delivered a live fetus, compared to 30.6% (15/49) women without such management, p < 0.001. CONCLUSION: Patients who underwent non-radical surgery had significantly higher pregnancy rates. Most pregnancies resulted in a viable fetus, but radical trachelectomy led to a higher rate of preterm births in the severe prematurity range. Half of the patients did not attempt pregnancy after FST.

Patterns of recurrence in FIGO stage IB1-IB2 cervical cancer: Comparison between minimally invasive and abdominal radical hysterectomy.

OBJECTIVE: Aim of our study was to evaluate whether the different laparotomic (ARH) or minimally invasive (laparoscopic and robotic) approaches (MIS) in FIGO stage IB1-IB2 cervical cancer, present different patterns of recurrence of the disease. The secondary endpoint of the study was the evaluation of the variables most involved with the risk of relapse and therefore lower DFS and OS. MATERIAL AND METHODS: The study enrolled patients with definitive histological diagnosis of squamous or adenocarcinoma stage IB1-IB2 cervical cancer who underwent minimally invasive or abdominal radical hysterectomy from 2001 to 2018. RESULTS: The study enrolled 360 patients and 59 patients (16.4 %) reported a disease relapse. The data showed that ARH group was not associated with different recurrence patterns than MIS group (p = 0.14). Moreover, there was no statistically significant difference regarding DFS (p = 0.52) and OS (p = 0.29) between the ARH group and the MIS group. CONCLUSIONS: MIS, in FIGO stage IB1-IB2 cervical cancer, is not associated with different relapse patterns compared to ARH, nor with a higher risk of distance metastasis and finally, without significant difference in term of DFS and OS. More studies are needed to determine the factors that modify the site of relapse.

Special Issue: "Management of Early Stage Cervical Cancer".

Cervical carcinoma is a common gynecological malignancy that remains a challenge for oncologic gynecologists around the world [...].

Clinical Impact of Pathologic Residual Tumor in Locally Advanced Cervical Cancer Patients Managed by Chemoradiotherapy Followed by Radical Surgery: A Large, Multicenter, Retrospective Study.

BACKGROUND: Exclusive chemoradiation (E-CT/RT) represents the standard of treatment for locally advanced cervical cancer (LACC). Chemoradiation (CT/RT) followed by radical surgery (RS) may play a role for patients with a suboptimal response to CT/RT or in low-income countries with limited access to radiotherapy. Histologic assessment of residual tumor after CT/RT and RS allows accurate definition of prognostic categories. METHODS: Data on patients with FIGO stages 1B2 to 4A cervical cancer managed by CT/RT and RS from June 1996 to March 2020 were retrospectively analyzed. Pathologic response on the cervix was defined as complete (pCR), microscopic (persistent tumor foci ≤ 3 mm) (pmicroR), or macroscopic (persistent tumor foci > 3 mm) (pmacroR). Lymph node (LN) residual tumor was classified as absent or present. RESULTS: The 701 patients in this study underwent CT/RT and RS. Of the 701 patients, 293 (41.8%) had pCR, 188 (26.8%) had pmicroR, and 220 (31.4%) had pMacroR. Residual tumor was found in the pelvic lymph nodes of 66 (9.4%) patients and the aortic lymph nodes of 29 (4.1%) patients. The 5-year DFS and OS were respectively 86.6% and 92.5% in the pCR cases, 80.3% and 89.1% in the pmicroR cases, and 56.2% and 68.8% in the pmacroR cases. Among the patients with lymph node residual tumor, the 5-year DFS and OS were respectively 16.7% and 40% in the pCR cases, 35.4% and 53.3% in the pmicroR cases, and 31.7% and 31.1% in the pmacroR cases. Cervical residual tumor,, positive pelvic LNs, and positive aortic LNs were associated with worse DFS and OS in both the uni- and multivariate analyses. CONCLUSIONS: Persistence of pathologic residual tumor on the cervix and LNs after CT/RT are reliable predictors of survival for LACC patients undergoing CT/RT and adjuvant surgery.

"Clock mapping" prior to excisional surgery in vulvar Paget's disease: tailoring the surgical plan.

INTRODUCTION: Paget disease is a rare neoplasm of the skin that mainly involves the vulvar region. Vulvar Paget's disease (VPD) can spread beyond the apparent edges of the lesion resulting in a high risk of involved surgical margins. Our aim is to verify the efficacy of a preoperative vulvo-vaginal intensive clock mapping in the prediction of the invasiveness and the extension of VPD. MATERIALS AND METHODS: All consecutive patients with primary VPD referred to our institution from July 2005 to December 2018 were subjected to a preoperative intensive biopsy mapping (clock mapping) of the vulvo-vaginal area: inside and outside the vulvar skin visible lesion, according to o'clock positions, and in the vagina. Patients with positive biopsies "only inside" or "also beyond" the visible lesion were included, respectively, in Group A and B. Surgical excision was drawn passing by the points with negative histology. Pathological findings of mapping biopsies were compared with those from radical surgery. RESULTS: A total of 28 women were enrolled. After clock mapping definitive histology: 17 (60.7%) and 11 (39.3%) patients were included in Group A and B. Definitive histology showed non-invasive, micro-invasive and invasive VPD, respectively, in 13 (46.4%), 11 (39.3%) and 4 (14.3%) patients, with 4 patients further upstaged. Overall, negative margins were found in 14 (50%) patients: 9 (32.1%) from Group A and 5 (17.9%) from Group B. In 23 cases (82.1%), clock mapping identified free surgical margins along the vulvo-perineal skin excision front. CONCLUSIONS: Preoperative clock mapping emerged as potentially useful workup tool to predict invasiveness and extension of VPD, to tailor surgical excision.

The role of semiquantitative evaluation of lympho-vascular space invasion in early stage cervical cancer patients.

OBJECTIVE: Lymph vascular space involvement (LVSI) is one of the most important prognostic factors in early stage cervical cancer. Its qualitative evaluation represents a milestone for patient risk stratification and treatment choice, but a semi-quantitative analysis of LVSI may offer a more truthful risk model, as already demonstrated for endometrial cancer. The present study aims to investigate the performances of a semi-quantitative evaluation of LVSI in terms of patient risk assessment. METHODS: In this retrospective study were enrolled patients underwent surgical treatment for early cervical cancer from January 2009 to October 2018. A semi-quantitative evaluation such as the "three-tiered approach" was used to classify the LVSI pathway: negative vs. focal vs. diffuse. RESULTS: Diffuse LVSI was found to be a risk factor for lymph node metastasis (OR: 9.844, p < 0.001), and parametrial involvement (OR: 5.566, p < 0.001). Lymph nodal recurrences were more frequent in diffuse LVSI group (LVSI negative vs. focal LVSI p = 0.369; LVSI negative vs. diffuse LVSI p = 0.002; Focal LVSI vs. diffuse LVSI p = 0.214); and so distant recurrences (LVSI negative vs. focal LVSI p = 0.623; LVSI negative vs. diffuse LVSI p = 0.002; Focal LVSI vs. diffuse LVSI p = 0.026). Patients with diffuse LVSI showed a worse disease-free survival (DFS) than patients with focal or absent involvement (DFS LVSI negative vs. focal LVSI p = 0.938; LVSI negative vs. diffuse LVSI p < 0.001; focal LVSI vs. diffuse LVSI p = 0.036). CONCLUSION: Semi-quantitative evaluation of LVSI may be useful to identify risk patients for shorter disease-free survival and lymphatic and distant recurrences in patients with early stage.

Laparoscopic supracervical hysterectomy and sacral colpopexy for pelvic organ prolapse with percutaneous surgical system: Results from a pilot study.

OBJECTIVE: The aim of the study was to report our preliminary experience of supracervical 2 hysterectomy followed by sacral colpopexy performed with the Percuvance ™ PSS in terms of feasibility, effectiveness and safety. STUDY DESIGN: Between Jan 2017 and Feb 2017 10 patients affected by POP were enrolled in the present study. All patients undergoing supracervical hysterectomy followed by sacral colpo-cervicopexy with the Percuvance ™ PSS. RESULTS: The reported series consisted of 10 patients undergoing supracervical hysterectomy followed by sacral colpopexy with a median age of 63 years (range 55-71 years) and a median BMI (body mass index) of 24 (range 21-26). A median operative time of 123 min (range 103-134 min) and a median estimated blood loss (EBL) of 40 ml (range 20-60 ml) were registered. No conversions to standard laparoscopy or laparotomy were required and no intraoperative complications occurred. At the discharge all patients were completely satisfied with the cosmetic result and postoperative pain control. During 3 months urogynecological follow-up no patient showed surgical anatomic failure (>2 POP-Q stage)and the degree of overall satisfaction of the cosmetic results was confirmed by the surgeon and the patient equally. CONCLUSIONS: The PSS supracervical hysterectomy plus sacral colpopexy is a feasible and effective approach with good results in terms of operative time, cosmesis, postoperative pain and length of hospitalization.

Laparoscopic Radical Hysterectomy After Concomitant Chemoradiation in Locally Advanced Cervical Cancer: A Prospective Phase II Study.

OBJECTIVE: To assess the feasibility of laparoscopic radical surgery in patients with locally advanced cervical cancer (LACC) who receive chemoradiation therapy (CT/RT). DESIGN: Prospective phase II study (Canadian Task Force classification II-1). INTERVENTION: Patients with LACC (FIGO stage IB2-III) were evaluated for accrual at the Gynecologic Oncology Unit of Catholic University, Rome/Campobasso. Neoadjuvant CT/RT included whole-pelvic irradiation (total dose, 45.0-50.4 Gy) combined with cisplatin and 5-fluorouracil. Objective response to treatment was evaluated according to Response Evaluation Criteria in Solid Tumors criteria. Laparoscopic radical hysterectomy (RH) plus pelvic and/or aortic lymphadenectomy was attempted within 6 to 8 weeks after CT/RT. The feasibility of laparoscopic RH, as well as the rate, pattern, and severity of early and late postoperative complications, were analyzed. RESULTS: Between January 2010 and October 2013, a total of 58 patients were enrolled into the study. After CT/RT, 23 patients (39.6%) underwent type B2 RH, 31 (53.4%) underwent type C1 RH, and 4 (6.9%) underwent type C2 RH. Pelvic lymphadenectomy was performed in all cases. Laparoscopic RH was feasible in 55 of 58 cases (feasibility rate, 94.8%). No intraoperative complications were recorded. During the observation period (median, 22 months; range, 5-50 months), there were 28 complications, of which only 21.4% were grade 2 complications and 14.3% were grade 3 complications. As of January 2015, disease recurrence was documented in 4 cases (6.9%). CONCLUSION: Total laparoscopic radical surgery is feasible in patients with LACC receiving preoperative CT/RT, providing perioperative outcomes comparable to those registered in early-stage disease.

Long-term prospective longitudinal evaluation of emotional distress and quality of life in cervical cancer patients who remained disease-free 2-years from diagnosis.

BACKGROUND: A long-term prospective assessment of QoL in cervical cancer patients is still lacking. Here, we provide the first 2-years prospective, longitudinal study evaluating emotional distress and QoL in early stage (ECC) and locally advanced (LACC) cervical cancer patients who remained disease-free 2-years from diagnosis. METHODS: The questionnaires: Hospital Anxiety and Depression Scale (HADS), Global Health Status items of EORTC QLQ-C30 (GHS), and EORTC QLQ-CX24 (CX24) have been administered by a dedicated team of psycho-oncologists, administered at baseline, and after 3, 6, 12 and 24 months from surgery The Generalized Linear Model for repeated measure was used to analyze modifications of QoL measures over time. RESULTS: In both groups, an early reduction of the percentage of patients with anxiety levels ≥11 was observed at the 3-month evaluation (ECC: 25.7% at baseline Vs 14.7% after 3 months, p value=0.001; LACC: 22.2% at baseline Vs 15.4% after 3 months, p value=0.001). Despite this favorable trend, after 2 years from diagnosis, 11.9% of ECC and 15.6% of LACC patients still showed an anxiety score ≥11. No significant changes over time were observed in term of Depression levels. Focusing on QoL issues, mean GHS and Sexual Activity scores showed an improvement over time in both groups compared to baseline (GHS: 5.7% difference for ECC, p value=0.001, and 11.0% in LACC, p value=0.001; SXA: 13.9% difference for ECC, p value=0.001; and 6.1% in LACC, p value=0.008). On the other hand, Body Image mean scores were significantly impaired by chemoradiation administration in LACC patients, without long-term recovery (7.5% difference, p value=0.001). Finally, in both groups, lymphedema (LY) and menopausal symptoms (MS) showed an early worsening which persisted 2-year after surgery (LY: 19.5% difference for ECC, p value=0.014, and 27.3% in LACC, p value=0.001; MS: 14.4% difference for ECC, p value=0.004, and 16.0% in LACC, p value=0.002). CONCLUSIONS: Despite a significant improvement over time, elevated anxiety levels are still detectable at 24 months after surgery in approximately 10% of cervical cancer patients. Much more attention should be focused on surgical/medical approaches able to minimize the negative impact of lymphedema and menopausal symptoms on QoL.