Possible candidate population for neoadjuvant chemotherapy in women with advanced ovarian cancer

ObjectiveTo examine trends and outcomes related to neoadjuvant chemotherapy (NACT) use for advanced ovarian cancer based on patient and tumor factors.MethodsThis retrospective cohort study queried the National Cancer Institute's Surveillance, Epidemiology, and End Results Program to examine women with stage III-IV high-grade serous ovarian carcinoma from 2010 to 2016. Propensity score inverse probability of treatment weighting was used to assess the age-, cancer stage-, and tumor extent-specific survival estimates related to NACT use.ResultsUtilization of NACT has significantly increased in older women (≥65 years; 48.4% relative increase), followed by stage IV disease (35.2% relative increase), and stage III disease (25.0% relative increase) (all, P-trend < 0.05). Women who received NACT had overall survival (OS) similar to those who had primary cytoreductive surgery (PCS) in older women (hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.95–1.20, P = 0.284), stage IV disease (HR 0.96, 95%CI 0.84–1.10, P = 0.564), and more disease extent cases (T3/N1/M1, HR 1.06, 95%CI 0.84–1.32, P = 0.640). Moreover, NACT use was associated with decreased other cause mortality risk compared to PCS in the older women (sub-distribution HR 0.61, 95%CI 0.40–0.94, P = 0.025) and stage IV disease (sub-distribution HR 0.49, 95%CI 0.27–0.90, P = 0.021). In contrast, women who received NACT had decreased OS compared to those who had PCS in the younger group (HR 1.22, 95%CI 1.07–1.38, P = 0.004), stage III disease (HR 1.26, 95%CI 1.13–1.41, P < 0.001), and lesser disease extent cases (T3/N0/M0, HR 1.38, 95%CI 1.20–1.58, P < 0.001).ConclusionOur study suggests that survival effect of NACT for advanced ovarian cancer may differ based on patient and tumor factors. In older women, stage IV disease, and greater disease extent, NACT was associated with similar OS compared to PCS.     

The survival detriment of venous thromboembolism with epithelial ovarian cancer

Objective

The aim of this study is to evaluate the effect of venous thromboembolism (VTE) chronology with respect to surgery on survival with epithelial ovarian cancer (EOC).

Methods

An IRB approved, retrospective review was performed of patients treated for Stage I–IV EOC from 1996 to 2011. Cox proportional hazards model was used to assess associations between VTE and the primary outcomes of progression free survival (PFS) and overall survival (OS). SAS 9.3 was used for statistical analyses.

Results

586 patients met study criteria. Median age was 63 years (range, 17–94); median BMI was 27.1 kg/m² (range, 13.7–67.0). Most tumors were high grade serous (68.3%) and advanced stage (III/IV, 75.4%). 3.7% had a preoperative VTE; 13.2% had a postoperative VTE. Upon multivariate analysis adjusting for age, stage, histology, performance status, and residual disease, preoperative VTE was predictive of OS (HR 3.1, 95% CI: 1.6–6.1, p = 0.001) but not PFS (p = 0.55). Postoperative VTE was associated with shorter PFS (HR 1.45, 95% CI: 1.04–2.02, p = 0.03) and OS (HR 1.8, 95% CI: 1.3–2.6, p = 0.001). When VTE timing was modeled, preoperative VTE (HR 3.5, 95% CI: 1.8–6.9, p < 0.001) and postoperative VTE after primary therapy (HR 2.3, 95% CI: 1.4–3.6, p = 0.001) were predictive of OS.

Conclusion

Preoperative and postoperative VTE appear to have a detrimental effect on OS with EOC. When modeled as a binary variable, postoperative VTE attenuated PFS; however, when VTE timing was modeled, postoperative VTE was not associated with PFS. It is unclear whether VTE is an inherent poor prognostic marker or if improved VTE prophylaxis and treatment may enable similar survival to patients without these events.     

Prognosis for advanced-stage primary peritoneal serous papillary carcinoma and serous ovarian cancer in Taiwan

ObjectiveTo compare the prognosis of patients with advanced-stage primary peritoneal serous papillary carcinoma (PSPC) or papillary serous ovarian cancer (PSOC).Materials and MethodsThis was a retrospective case–control study and included two study groups: one with stage III/IV PSPC (n = 38) patients and the other with PSOC (n = 53) patients. Patients were matched for histologic subtype (serous tumor), tumor stage, tumor grade, residual disease at the end of debulking surgery (primary or interval), and age (±5 years).ResultsMean age was significantly greater for patients with PSPC (63.03 ± 11.88 years) than for patients with PSOC (55.92 ± 12.56 years, p = 0.008). Optimal debulking surgery was performed initially in 71.9% of PSPC patients and 66.0% of PSOC patients. In addition, 93.9% of PSPC patients and 92.3% of PSOC patients were treated with platinum–paclitaxel chemotherapy. The frequency of high-grade tumors was significantly higher in the PSPC (100%) than in the PSOC group (68.3%; p < 0.001). Progression-free survival (PFS) was similar in the PSPC [median 12 months, 95% confidence interval (CI) 7.3–16.7] and PSOC groups (median 16.7 months, 95% CI 12.9–20.4; p = 0.470). Overall survival was shorter in the PSPC (median 62 months, 95% CI 19.6–104.4) than in the PSOC group (median 77.5 months, 95% CI 69.7–85.2; p = 0.006, log-rank statistic).ConclusionPFS was similar for advanced-stage PSPC and PSOC patients. Since the PSPC patients tended to be older and have more high-grade tumors, OS was shorter for PSPC than for POSC patients. Thus, management of the two types of cancer should not differ.     

Old versus new FIGO staging systems in predicting overall survival in patients with uterine leiomyosarcoma: A study of 86 cases

ObjectivesUterine leiomyosarcoma (uLMS) was staged using the FIGO system for endometrial cancers. The new FIGO system takes into consideration tumor size disregarding myometrial and cervical involvement. We aimed to compare the two systems and see which more accurately predicts overall survival (OS).Methods86 patients with uLMS (1984–2010) were retrospectively staged using both FIGO systems. Mean OS rates were estimated using the Kaplan–Meier method.ResultsMore patients had stage-I disease by the new FIGO system (42 versus 33). Five versus 18 and 27 versus 5 had old and new stage-II and III diseases respectively. Five and 4 patients with old stage II and III uLMS respectively were downstaged to stage I while 18 with old stage III were downstaged to stage II. Median follow-up was 23.5 months with a median OS of 114 (95% CI, 61–166) months. Although patients with stage I tumors had a higher mean OS rate compared to those with higher stage disease by either system, patients with old stage II–IV disease showed similar mean OS rates, with stage III–IV patients having a slightly better mean OS and a similar trend was observed with the new system. Patients with new FIGO stage III had a higher mean OS rate than those with stage II or IV disease (37.6 versus 28.1 and 34.3 months). Nonetheless, no statistical significant differences were seen in OS according to stage using either system (p = 0.786 and p = 0.400 respectively).ConclusionNeither FIGO staging system is ideal in classifying patients into four clinically significant stages.     

Does neoadjuvant chemotherapy impair long-term survival for ovarian cancer patients? A nationwide Danish study

Objective

In Denmark, the proportion of women with ovarian cancer treated with neoadjuvant chemotherapy (NACT) has increased, and the use of NACT varies among center hospitals. We aimed to evaluate the impact of first-line treatment on surgical outcome and median overall survival (MOS).

Methods

All patients treated in Danish referral centers with stage IIIC or IV epithelial ovarian cancer from January 2005 to October 2011 were included. Data were obtained from the Danish Gynecological Cancer Database, the Danish National Patient Register and medical records.

Results

Of the 1677 eligible patients, 990 (59%) were treated with primary debulking surgery (PDS), 515 (31%) with NACT, and 172 (10%) received palliative treatment. Of the patients referred to NACT, 335 (65%) received interval debulking surgery (IDS). Patients treated with NACT–IDS had shorter operation times, less blood loss, less extensive surgery, fewer intraoperative complications and a lower frequency of residual tumor (p < 0.05 for all). No difference in MOS was found between patients treated with PDS (31.9 months) and patients treated with NACT–IDS (29.4 months), p = 0.099. Patients without residual tumor after surgery had better MOS when treated with PDS compared with NACT–IDS (55.5 and 36.7 months, respectively, p = 0.002). In a multivariate analysis, NACT–IDS was associated with increased risk of death after two years of follow-up (HR: 1.81; CI: 1.39–2.35).

Conclusions

No difference in MOS was observed between PDS and NACT–IDS. However, patients without residual tumor had superior MOS when treated with PDS, and NACT–IDS could be associated with increased risk of death after two years of follow-up.     

A multicenter evaluation of adjuvant therapy in women with optimally resected stage IIIC endometrial cancer

ObjectiveTo determine if there is an advantage to combination chemotherapy and radiation for optimally resected stage IIIC endometrial cancer (EC).MethodsA multicenter retrospective analysis of patients with EC from 1991 to 2008 was conducted. Inclusion criteria were lymph node assessment and optimally resected disease. Recurrence-free (RFS) and overall survival (OS) were analyzed using Kaplan–Meier method and Cox proportional hazards model.Results265 patients with optimally resected stage IIIC EC were identified. Postoperative therapies included radiotherapy in 17% (n = 45), chemotherapy in 17% (n = 46), and both chemotherapy and radiation in 61% (n = 161). Three-year RFS was 56% for chemotherapy alone, compared to 73% for radiation alone, and 73% for combination therapy (p = 0.12). Those receiving chemotherapy alone had the worst 3-year OS (78%) compared to either radiotherapy alone (95%) or combination therapy (90%) (p = 0.005). After adjustment for stage and grade those treated with chemotherapy alone were at a 2.2 fold increased risk of recurrence (95% CI, 1.2 to 4.2; p = 0.02) and 4.0 fold increased risk of death (95% CI, 1.6 to 10.0; p = 0.004) compared to those treated with chemotherapy and radiation. In contrast there was no significant difference in RFS [HR = 1.0 (95% CI, 0.5 to 2.0; p = 0.92)] or OS [HR = 1.1 (95% CI, 0.3 to 3.6; p = 0.91)] for those treated with radiation alone compared to those treated with chemotherapy and radiation.ConclusionAdjuvant therapy with either radiation alone or chemotherapy and radiation was associated with improved outcomes for patients with optimally resected stage IIIC EC compared to those treated with chemotherapy only.     

Surgical outcome prediction in patients with advanced ovarian cancer using computed tomography scans and intraoperative findings

ObjectiveThis study aimed to identify features on preoperative computed tomography (CT) scans that are predictive of suboptimal primary cytoreduction and to evaluate the correlation between CT findings and intraoperative findings in advanced ovarian cancer.Materials and methodsWe retrospectively reviewed preoperative CT scans and operative findings from patients with stage III/IV epithelial ovarian cancer who underwent primary cytoreduction between 2003 and 2006. Fourteen criteria were assessed. Clinical data were extracted from medical records. Residual tumors measuring ≥1 cm were considered suboptimal.ResultsWe retrospectively identified 118 patients who met the study inclusion criteria. The rate of optimal cytoreduction (≤1 cm residual disease) was 40%. On preoperative CT scans, omental extension to the stomach or spleen and inguinal or pelvic lymph nodes >2 cm were predictors of suboptimal cytoreduction on univariate (p = 0.016 and p = 0.028, respectively) and multivariate analysis (p = 0.042 and p = 0.029, respectively). Involvement of both omental extension and inguinal or pelvic lymph nodes had a positive predictive value (PPV) of 100%, a specificity of 100%, and an accuracy of 45.8% in predicting suboptimal cytoreduction. We correlated the preoperative CT findings with the intraoperative findings. There were significant correlations between CT and intraoperative findings of omental extension (p = 0.007), inguinal or pelvic lymph nodes >2 cm (p < 0.001), and large bowel mesentery implants >2 cm (p = 0.001).ConclusionThe combination of omental extension to the stomach or spleen and involvement of inguinal or pelvic lymph nodes in preoperative CT scans is considered predictive of suboptimal cytoreduction. These patients may be more appropriately treated with neoadjuvant chemotherapy followed by surgical cytoreduction.     

Long-term outcomes of concomitant cisplatin plus radiotherapy versus radiotherapy alone in patients with stage IIIB squamous cervical cancer: A randomized controlled trial

ObjectiveThe present analysis determined the disease free survival (DFS) and overall survival (OS) at up to 14 years of follow-up in women who participated in our previous phase 3 randomized controlled clinical trial, in which women with stage IIIB squamous cervical cancer received either cisplatin plus RT or RT alone for treatment. The first study showed that the addition of cisplatin to RT offered a significant benefit in DFS, but not in OS.MethodsThe present analysis examined DFS and OS in 146 women from the original cohort (72 patients in the CRT arm and 74 patients in the RT-only arm) with follow-up of up to 14 years.ResultsLonger term follow-up showed that treatment with CRT offers a significant benefit in DFS and OS compared with treatment with RT only. Patients who received RT alone had significantly worse OS (HR, 1.88; 95% CI, 1.09–3.24) and DFS (HR, 1.82; 95% CI, 1.07–3.08) compared with patients who received CRT. The multivariate analyses also showed that the patients with baseline Karnofsky performance status (KPS) <90% showed significantly worse OS (HR, 3.11; 95% CI, 1.78–5.43), as did those with hemoglobin <10 mg/dL (HR, 4.32; 95% CI, 2.23–8.36). Patients with baseline KPS < 90% showed significantly worse DFS (HR, 2.83; 95% CI, 1.60–5.01), as did those with hemoglobin <10 mg/dL (HR, 4.16; 95% CI, 2.17–7.95).ConclusionsFor stage IIIB cervical cancer, treatment with CRT offers a significant benefit in DFS and OS compared with treatment with RT only.     

Neoadjuvant chemotherapy increases the 5-year overall survival of patients with resectable cervical cancer: A systematic review and meta-analysis

Cervical cancer is a global health challenge in women. Neoadjuvant chemotherapy (NACT) is a recent prospect for alternative cervical cancer treatments. This study investigated the efficacy of NACT against resectable cervical cancer based on the medium and long-term survival of patients with the disease. We searched through PubMed, Web of Science, EBSCO and Cochrane Library for relevant reports published by June 2020. The primary outcomes were 3-year and 5-year progression-free survival (PFS) and overall survival (OS) of patients with resectable cervical cancer. Overall, 22 publications encompassing 5627 patients fulfilled the inclusion criteria. We found NACT not to affect both 3-year PFS and OS as well as 5-year PFS of patients with resectable cervical cancer. However, NACT significantly improves the 5-year OS of patients with resectable cervical cancer (HR = 0.83, 95% CI: 0.73–0.94, p = 0.013). Subgroup analysis (RCTs, non-RCTs, NACT + surgery + AT vs. surgery + AT, NACT + surgery + AT vs. CCRT/RT/CRT) further revealed NACT had no significant effect on 5-year PFS of patients with resectable cervical cancer, converse to the 5-year OS subgroup analysis, which validated the beneficial effect of NACT in patients with resectable cervical cancer. In addition, the effect of NACT was most significant in the non-RCTs subgroup (p = 0.012). NACT may improve the long-term prognosis of patients with resectable cervical cancer. However, further large-scale multicenter studies are needed to validate this finding.     

Adjuvant therapy in patients with clear cell endometrial carcinoma: An analysis of the National Cancer Database

Objective

To assess the impact of adjuvant treatment, sociodemographic and tumor factors on the survival of patients with non-metastatic clear cell endometrial carcinoma (CCC).

The Importance of Surgical Staging in Women With Uterine Serous Carcinoma: Experience in a Single Institution Reveals a Survival Benefit

ObjectiveTo assess the appropriate extent of surgical staging in women with clinically early stage uterine serous carcinoma (USC).MethodsWe conducted a single-institution retrospective cohort study of all women with USC between 2007 and 2012. Treatment practices, outcomes, and factors affecting survival were analyzed using univariate and multivariate analysis.ResultsEighty-four patients were identified, 76 of whom were included in the analysis. Preoperative pathology correctly identified USC in 73.3% of cases. Surgical stage distribution was 44.7% stage I, 7.9% stage II, 31.6% stage III, and 15.8% stage IV. Women thought to have early stage disease preoperatively encompassed 84.2% (64) of the cohort. Fifty-two (81.3%) of these women with clinically early stage disease had complete surgical staging. Thirty-four (53.1%) were determined to have surgical stage I, and the remaining 30 (46.9%) had occult advanced stage disease. Median follow-up was 43.2 months. Univariate analysis found a significant increase in progression-free survival and overall survival for women with clinically early stage disease with positive lymphovascular space invasion (P < 0.001 and P = 0.002, respectively), positive peritoneal cytology (P = 0.022 and P = 0.04, respectively), early stage (P < 0.001 and P = 0.004, respectively), and elevated serum CA125 at diagnosis (P = 0.003 and P = 0.001, respectively). On multivariate analysis, early stage (hazard ratio [HR] 9.87; 95% CI 2.79 to 34.92, P < 0.001) and complete surgical staging (HR 2.96; 95% CI 1.05 to 8.37, P = 0.040) were associated with prolonged progression-free survival, while overall survival was not affected by complete surgical staging (HR 1.92; 95% CI 0.64 to 5.76, P = 0.79).ConclusionComplete surgical staging prolongs the progression-free survival of women with clinical early-stage uterine serous cancer. Although this does not extend to overall survival, this enables patients to have an improved quality of life with a longer interval without the burden of disease.     

Is Diagnostic Hysteroscopy Safe for the Investigation of Type II Endometrial Cancer? A Retrospective Cohort Analysis

Study ObjectiveAlthough hysteroscopy (HSC) can be used for assessing the uterine cavity in women with suspected endometrial cancer (EC), it remains controversial as a procedure because it can potentially enhance the metastatic spread of cancer cells. Moreover, it is important to assess this hypothesis for type II EC, a more aggressive phenotype that usually presents with endometrial atrophy and has worse prognosis. Thus, we aimed to assess the prevalence of positive peritoneal cytology result in women with type II EC who underwent HSC as a diagnostic tool and to determine the factors associated with patient relapse/survival.DesignRetrospective cohort analysis (2002–2017).SettingTertiary, academic hospital.PatientsOne hundred twenty-seven women with type II EC.InterventionsDiagnostic HSC (HSC) (n = 43) or dilation/curettage (D&C) (n = 84).Measurements and Main ResultsPrimary end point was the frequency of positive peritoneal cytology result. Survival curves were projected using the Kaplan-Meier method and compared using the log-rank test. Cox regression analysis with hazard ratio (HR) and 95% confidence intervals (CIs) were calculated to assess the factors related with the disease-free survival (DFS) and the disease-specific survival (DSS). Advanced cancer stage and greater vascular invasion appeared more frequently in the D&C group (p = .008 and p = .04, respectively). Positive peritoneal cytology result was present in 2 of 43 (4.6%) women following HSC and in 9 of 84 (10.7%) following D&C (p = .22). DFS and DSS curves did not statistically differ between the groups. Multivariate analysis for DFS revealed that advanced cancer stage (III and IV) (HR = 4.67; 95% CI, 2.34–9.34; p <.001) and advanced age (HR = 1.08; 95% CI, 1.04–1.13]; p <.001) were the factors associated with relapse. For DSS, advanced age (HR = 1.08; 95% CI, 1.05–1.12; p <.001), cancer stage III/IV (HR = 3.95; 95% CI, 2.18–7.15; p <.001), and vascular invasion (HR = 2.47; 95% CI, 1.34–4.54; p = .004) increased the risk of mortality.ConclusionDiagnostic HSC did not increase the rate of positive peritoneal cytology result at the time of surgical staging in this cohort of women with type II EC and is probably as safe as D&C.     

Maintained survival outcome after reducing lymphadenectomy rates and optimizing adjuvant treatment in endometrial cancer

ObjectiveMain controversies in endometrial cancer treatment include the role of lymphadenectomy and optimal adjuvant treatment. We assessed clinical outcome in a population-based endometrial cancer cohort in relation to changes in treatment management over two decades.MethodsAll consenting endometrial cancer patients receiving primary treatment at Haukeland University Hospital from 2001 to 2019 were included (n = 1308). Clinicopathological variables were evaluated for year-to-year changes. Clinical outcome before and after discontinuing adjuvant radiotherapy and individualizing extent of lymphadenectomy was analyzed.ResultsThe rate of lymphadenectomy was reduced from 78% in 2001–2012 to 53% in 2013–2019. The rate of patients with verified lymph node metastases was maintained (9% vs 8%, p = 0.58) and FIGO stage I patients who did not undergo lymphadenectomy had stable 3-year recurrence-free survival (88% vs 90%, p = 0.67). Adjuvant chemotherapy for completely resected FIGO stage III patients increased from 27% to 97% from 2001 to 2009 to 2010–2019, while adjuvant radiotherapy declined from 57% to 0% (p < 0.001). These patients had improved 5-year overall- and recurrence-free survival; 0.49 [95% CI: 0.37–0.65] in 2001–2009 compared to 0.61 [0.45–0.83] in 2010–2019, p = 0.04 and 0.51 [0.39–0.68] to 0.71 [0.60–0.85], p = 0.03, respectively. For stage I, II and IV, survival rates were unchanged.ConclusionsOur study demonstrates that preoperative stratification by imaging and histological assessments permits a reduction in lymphadenectomy to around 50%, and is achievable without an increase in recurrences at 3 years. In addition, our findings support that adjuvant chemotherapy alone performs equally to adjuvant radiotherapy with regard to survival, and is likely superior in advanced stage patients.     

Survival outcomes of acute normovolemic hemodilution in patients undergoing primary debulking surgery for advanced ovarian cancer: A Memorial Sloan Kettering Cancer Center Team Ovary study

ObjectiveTo describe oncologic outcomes after using acute normovolemic hemodilution (ANH) to reduce requirement for allogenic red blood cell transfusions (ABT) in patients undergoing primary debulking surgery (PDS) for advanced ovarian cancer.MethodsWe performed a post-hoc analysis of a recent prospective trial investigating the safety and feasibility of ANH during PDS for advanced ovarian cancer. We report long-term survival outcomes. We compared demographics, clinicopathological characteristics, survival outcomes in this cohort of Stage IIIB-IVB high-grade serous ovarian cancer patients undergoing ANH (ANH group), with a retrospective cohort of all other patients (standard group) undergoing PDS during the same time period (01/2012–04/2017). Standard statistical tests were used.ResultsThere were no demographic or clinicopathological differences between ANH (n = 33) and standard groups (n = 360), except for higher median age at diagnosis (57 vs. 62 years, respectively; p = 0.044) and shorter operative time (357 vs. 446 min, respectively; p < 0.001) in the standard group. Cytoreductive outcomes (ANH vs. standard): 0 mm, 69.7 vs. 63.9%; gross residual disease (RD) ≤1 cm, 21.2 vs. 26.9%; >1 cm, 9.1 vs. 9.2% (p = 0.78). RD after PDS was the only independent factor associated with worse progression-free survival (PFS) on multivariable analysis (p < 0.001). Patients with BRCA mutations trended towards improved PFS (p = 0.057). Significant factors for overall survival (OS) on multivariable analysis: preoperative CA125 (p = 0.004), ascites (p = 0.018), RD after PDS (p = 0.04), BRCA mutation status (p < 0.001). After adjustment for potential confounders, ANH was not independently associated with PFS or OS [PFS: HR 0.928 (0.618–1.395); p = 0.721; OS: HR 0.588 (95%CI: 0.317–1.092); p = 0.093].ConclusionsANH is an innovative approach in intraoperative management. It was previously proven to decrease need for ABT while maintaining the ability to achieve complete gross resection and associated benefits.     

Impact of tubal ligation on routes of dissemination and overall survival in uterine serous carcinoma

ObjectiveAbdominal peritoneal implants are characteristic of uterine serous carcinoma (USC). The presumed mechanism of dissemination is retrograde transit via the fallopian tube. We assessed the impact of tubal ligation (TL) on the metastatic profile and survival of USC patients.MethodsPatient risk factors, process-of-care variables, and disease-specific parameters were annotated. Categorical variables were compared using the χ² test. Overall survival (OS) was estimated via the Kaplan–Meier method.ResultsAmong 211 USC patients, fallopian tube status was documented in 142 patients; 35 had a history of TL and 107 did not. When comparing patients with and without TL, positive peritoneal cytology was present, respectively, in 18.8% vs 45.0% (P = .01) and stage IV disease in 14.3% vs 34.6% (P = .02). Using Cox models, age was the sole significant determinant of OS in stage I/II USC. By contrast, age, lymphovascular space involvement, positive cytology, and TL independently and adversely affected survival in stage III/IV USC. Adjusting for these factors in a multivariable model, the association between TL and OS among patients with advanced disease yielded a hazard ratio of 8.61 (95% CI, 3.08–24.03; P < .001). The prevalence of lymphatic metastasis and nodal tumor burden was significantly greater in patients who underwent ligation.ConclusionPatients with TL had significantly lower rates of positive cytology and stage IV disease than patients without TL. The lymphatic system appeared to be the dominant mode of spread after TL and was associated with a paradoxic worsening of OS, perhaps reflecting a delay in diagnosis.     

Uterine adenosarcoma: An analysis on management,outcomes, and risk factors for recurrence

ObjectivesUterine adenosarcoma is a rare malignancy with little data on optimal management. We aimed to clarify the impact of adjuvant therapy in patients with uterine adenosarcoma and identify risk factors for recurrence and death.MethodsWe performed a retrospective review of patients undergoing primary evaluation and treatment for uterine adenosarcoma at a single institution from July 1982 through December 2011. Univariate and multivariate analyses were used to identify prognostic factors for progression-free survival (PFS) and overall survival (OS).ResultsWe identified 100 patients with uterine adenosarcoma, and 74 patients met the inclusion criteria. On multivariate analysis, sarcomatous overgrowth (SO) and lymphovascular space invasion (LVSI) were predictors of worse PFS and OS. Median PFS and OS were 29.4 and 55.4 months for patients with SO, compared to 105.9 and 112.4 months for patients without SO (PFS HR 2.58, 95% CI 1.37–4.84, p = 0.003; OS HR 2.45, 95% CI 1.26–4.76, p = 0.008). Among patients with stage I disease, 17 of 22 patients (77%) with SO and 8 of 37 patients (22%) without SO had a recurrence (p < 0.001). Among patients with stage I disease with SO, adjuvant therapy appeared to be associated with longer PFS and OS, but these differences were not statistically significant (PFS, 46.7 vs. 29.4 months, p = 0.28; OS, 97.3 vs. 55.4 months, p = 0.18).ConclusionIn patients with uterine adenosarcoma, the presence of SO or LVSI confers a higher risk of recurrence. We did not identify an optimal treatment strategy for patients with SO, but adjuvant therapy may be associated with prolonged PFS.     

Prognostic value of responsiveness of neoadjuvant chemotherapy before surgery for patients with stage IB2/IIA2 cervical cancer

ObjectiveTo evaluate the factors that might affect the putative survival benefit from pre-operative neoadjuvant chemotherapy (NAC) in patients with early stage bulky cervical cancer.MethodsA retrospective review for 304 patients with stage IB₂/IIA₂ cervical cancer was performed. Two groups were made according to pre-operative NAC or not: NAC group (n = 154) and primary surgery group (PST, n = 150). Recurrence risks and survival were analyzed.ResultsThe total response rate was 72.1%. For those NAC-responders, NAC decreased the ratio of lymphovascular space invasion (0 vs. 4.7%, p = 0.022; 0 vs. 3.3%, p = 0.052), deep stromal invasion (19.8% vs. 53.5%, p = 0.000; 19.8% vs. 29.3%, p = 0.08), lymph node metastasis (8.1% vs. 25.6%, p = 0.004; 8.1% vs. 17.3%, p = 0.031), and the need of adjuvant radiotherapy (5.5% vs. 30.2%, p = 0.000; 5.4% vs. 15.3%, p = 0.012), whereas improve 5-year PFS rate (94% vs. 86%, p = 0.041; 94% vs. 80%, p = 0.089) and 5-year OS rate (96% vs. 86%, p = 0.015; 96% vs. 82%, p = 0.05), as compared with non-responders and PST. Multivariate analysis suggested that the response to NAC is an independent prognostic factor of PFS (HR 0.221, 95% CI 0.048–1.022, p = 0.053) and OS (HR 0.126, 95% CI 0.016–1.000, p = 0.05); as compared, stage IIA disease demonstrates negative impact upon PFS (HR 4.778, 95% CI 1.490–15.317, p = 0.009) and OS (HR 4.142, 95% CI 1.258–13.639, p = 0.019).ConclusionResponsiveness of NAC before surgery might be an independent prognostic factor for the patients with early stage bulky cervical cancer.     

Labour duration and timing of interventions in women planning vaginal birth after caesarean section

Objectiveunderstanding the labour characteristics of women attempting vaginal birth after caesarean (VBAC) may suggest how to improve intrapartum management and may enhance success rates. Promoting VBAC is a relevant factor in decreasing overall caesarean section (c-section) rates. However, the labour processes of women attempting VBAC are not well investigated. The aim of this paper is to compare multiparae planning a first VBAC (pVBAC) with primiparae and with multiparae planning a second vaginal birth, all starting to give birth vaginally, with regard to (a) perinatal characteristics, (b) the timing of intrapartal spontaneous rupture of membranes (SROM) and of interventions, and (c) labour duration, with respect to the first and second stages.Settingcohort study of women planning vaginal birth in 47 obstetric units in Lower Saxony, Germany.Participants1897 primiparae, 211 multiparae with one previous c-section and 1149 multiparae with one previous vaginal birth.Measurementssecondary analysis of data from an existing cohort study. Kaplan–Meier estimates, log rank test, Wilcoxon test and shared frailty Cox regression models including time-varying covariates were used to compare the timing of interventions and labour duration between the subsamples. Analyses were done with the statistics programme Stata 13.Findingsperinatal and labour characteristics of multiparae with pVBAC mainly resembled those of primiparae and differed from those of multiparae planning a second vaginal birth. However, compared to primiparae, multiparae with pVBAC received oxytocin less often (48.82 versus 56.95%, p=0.024) and gave birth vaginally significantly less often (69.19 versus 83.40%, p<0.001). The timing of intrapartal SROM (2.67 versus 3.42 hours, p=0.112) and of interventions (amniotomy: 5.50 versus 5.83 hours, p=0.198; oxytocin: 5.75 versus 6.00 hours, p=0.596; epidural: 4.00 versus 4.67 hours, p=0.416; opioids: 3.83 versus 3.78, p=0.851) was similar to that in primiparae although timings of all interventions but not of SROM differed significantly from that in multiparae with second vaginal birth (SROM: 2.67 versus 2.67 hours, p=0.481; amniotomy: 5.50 versus 3.93 hours, p<0.001; oxytocin: 5.75 versus 4.25 hours, p<0.001; epidural: 4.00 versus 3.50 hours, p=0.009; 3.83 versus. 2.75 hours, p=0.026). Overall and first-stage labour duration were comparable to primiparae (overall labour duration: 8.83 versus 8.57 hours, HR=0.998, 95% CI=0.830−1.201, p=0.987; first stage: 7.42 versus 7.00 hours, HR=0.916, 95% CI=0.774-1.083, p=0.303) but significantly longer than in other multiparae (overall labour duration: 8.83 versus 4.63 hours, HR=0.319, 95% CI=0.265−0.385, p<0.001; first stage: 7.42 versus 4.25 hours, HR=0.402, 95% CI=0.339-0.478, p<0.001). However, the second stage of labour was significantly shorter in multiparae with pVBAC than in primiparae (0.55 versus 0.77 hours, HR=1.341, 95% CI=1.049−1.714, p=0.019), but longer than in multiparae with second vaginal birth (0.55 versus 0.22 hours, HR=0.334, 95% CI=0.262–0.426, p<0.001).Key conclusionlabour patterns of multiparous women planning a VBAC differ from those of primiparae and other multiparous women. Multiparae with pVBAC should be considered as a distinct group of parturients.Implication for practiceexpectations regarding labour progression for multiparae with first pVBAC should be similar to those for primiparae. However, the chance that the second stage of labour might be shorter than in primiparae is relevant and motivating information for pregnant women with a previous c-section in deciding the planned mode of birth.     

Is there any therapeutic role of pelvic and para-aortic lymphadenectomy in apparent early stage epithelial ovarian cancer?

ObjectiveThe therapeutic role of pelvic and para-aortic lymphadenectomy in surgical staging of apparent early-stage epithelial ovarian cancer (eEOC) is still under debate. The aim of this study was to evaluate the potential therapeutic role of systematic lymphadenectomy in patients with eEOC.MethodsMulti-center retrospective cohort study, comparing women with apparent eEOC who underwent comprehensive bilateral pelvic and para-aortic lymphadenectomy (defined as ≥20 lymph nodes) versus patients receiving no lymphadenectomy or lymph node sampling, from 05/1985 to 12/2016. Patients with bulky nodes at CT-scan and those without complete intra-peritoneal surgical staging were excluded. Only patients who received at least 3 cycles of platinum-based adjuvant chemotherapy were included.ResultsOut of 2559 patients with FIGO stage IA-IIIA1 ovarian cancer, 639 (25.0%) met inclusion criteria. 360 (56.3%) underwent comprehensive lymphadenectomy, 150 (23.5%) lymph node sampling and 129 (20.2%) no lymphadenectomy. Patients who underwent comprehensive lymphadenectomy were younger (p < 0.001), experienced a higher number of severe post-operative complications (p = 0.008) and had a longer time to start chemotherapy (p = 0.034). There was no difference in intra-operative complications. Median follow-up was 63 months (range, 5–342). The 5-year disease-free survival (DFS) was 79.7% vs. 76.5% vs. 68.3% (p = 0.006), and 5-year overall survival (OS) was 92.3% vs. 94.5% vs. 89.8% (p = 0.165) in women who received comprehensive lymphadenectomy vs. lymph node sampling vs. no lymphadenectomy, respectively. Lymphadenectomy represented an independent factor for DFS improvement, HR 0.52 (95%CI 0.37–0.73) (p < 0.001).ConclusionPelvic and para-aortic lymphadenectomy in surgical staging of eEOC improves DFS for the price of increasing post-operative complications and time to chemotherapy but does not affect OS. Better understanding of tumor biology may help to identify those patients in whom lymphadenectomy should still play a role.