Long-term outcomes of R-CEOP show curative potential in patients with DLBCL and a contraindication to anthracyclines.

Doxorubicin plays an integral role in the treatment of patients with diffuse large B-cell lymphoma (DLBCL) but can be associated with significant toxicity. Treatment guidelines of British Columbia (BC) Cancer recommend the substitution of etoposide for doxorubicin in standard-dose R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) (R-CEOP) for patients who have a contraindication to anthracyclines; however, it is unknown if this compromises treatment outcome. We identified all patients with newly diagnosed DLBCL who were treated in BC with curative intent with R-CEOP (n = 70) within the study period. Outcome in this population was compared with a 2:1 case-matched control group (n = 140) treated with R-CHOP and matched for age, clinical stage, and International Prognostic Index score. The 10-year time to progression and disease-specific survival were not significantly different for patients treated with R-CEOP compared with patients in the R-CHOP control group (53% vs 62% [P = .089] and 58% vs 67% [P = .251], respectively). The 10-year overall survival was lower in the R-CEOP group (30% vs 49%, P = .002), reflecting the impact of underlying comorbidities and frailty of this population. R-CEOP represents a useful treatment alternative for patients with DLBCL and an absolute contraindication to the use of anthracyclines, with curative potential.

Adjuvant Treatment of Early Ovarian Clear Cell Carcinoma: A Population-Based Study of Whole Abdominal Versus Pelvic Nodal Radiotherapy.

BACKGROUND: Adjuvant treatment in early ovarian clear cell carcinoma (OCCC) is not yet standardized. The objective of this population-based study was to compare the outcome of patients with early OCCC treated with adjuvant chemotherapy versus chemoradiotherapy (chemoRT) and evaluate the association of adjuvant radiotherapy regimens (whole abdominal radiotherapy [WART] versus pelvic nodal radiotherapy [PRT]) with outcome. PATIENTS AND METHODS: Chart review was conducted to identify patients with stage I and II OCCC with complete information on staging. Patients with stage IA, IB, or IC OCCC purely resulting from capsular rupture were excluded because the provincial protocol does not recommend adjuvant treatment. RESULTS: Overall, 403 patients were identified and 343 received adjuvant treatment, of whom 255 had stage IC or II OCCC and 153 were eligible for final analysis. On Cox multivariable regression, receipt of chemoRT (n=90) was associated with an improvement in failure-free survival (FFS) (hazard ratio [HR], 0.57; 95% CI, 0.34-0.94) compared with chemotherapy alone (n=63). Use of chemoRT also resulted in 54% reduction in the cumulative incidence of cancer-specific mortality (subdistribution HR, 0.46; 95% CI, 0.24-0.89). However, there was no significant difference in the HR for overall survival (OS) between the chemoRT (HR, 0.70; 95% CI, 0.43-1.13) and chemotherapy group. Relative to chemotherapy + WART (chemo-WART), chemotherapy + PRT (chemo-PRT) was not associated with any significant difference in HR for FFS (HR, 1.34; 95% CI, 0.40-4.44) or OS (HR, 1.13; 95% CI, 0.37-3.46). CONCLUSIONS: Adjuvant chemoRT was associated with a lower risk of failure compared with chemotherapy alone. However, there was no difference in OS between the adjuvant chemotherapy and chemoRT regimens. Additionally, no significant difference in terms of FFS or OS was found between the chemo-WART and chemo-PRT groups.

Low junctional adhesion molecule-A expression is associated with an epithelial to mesenchymal transition and poorer outcomes in high-grade serous carcinoma of uterine adnexa.

High-grade serous carcinoma of uterine adnexa (HGSC) is the most frequent histotype of epithelial ovarian cancer and has a poor 5-year survival rate due to late-stage diagnosis and the poor efficacy of standard treatments. Novel biomarkers of cancer outcome are needed to identify new targetable pathways and improve personalized treatments. Cell-surface screening of 26 HGSC cell lines by high-throughput flow cytometry identified junctional adhesion molecule 1 (JAM-A, also known as F11R) as a potential biomarker. Using a multi-labeled immunofluorescent staining coupled with digital image analysis, protein levels of JAM-A were quantified in tissue microarrays from three HGSC patient cohorts: a discovery cohort (n = 101), the Canadian Ovarian Experimental Unified Resource cohort (COEUR, n = 1158), and the Canadian Cancer Trials Group OV16 cohort (n = 267). Low JAM-A level was associated with poorer outcome in the three cohorts by Kaplan-Meier (p = 0.023, p < 0.001, and p = 0.036, respectively) and was an independent marker of shorter survival in the COEUR cohort (HR = 0.517 (0.381-703), p < 0.001). When analyses were restricted to patients treated by taxane-platinum-based chemotherapy, low JAM-A protein expression was associated with poorer responses in the COEUR (p < 0.001) and OV16 cohorts (p = 0.006) by Kaplan-Meier. Decreased JAM-A gene expression was an indicator of poor outcome in gene expression datasets including The Cancer Genome Atlas (n = 606, p = 0.002) and Kaplan-Meier plotter (n = 1816, p = 0.024). Finally, we observed that tumors with decreased JAM-A expression exhibited an enhanced epithelial to mesenchymal transition (EMT) signature. Our results demonstrate that JAM-A expression is a robust prognostic biomarker of HGSC and may be used to discriminate tumors responsive to therapies targeting EMT.

Canadian cost-effectiveness model of BRCA-driven surgical prevention of breast/ovarian cancers compared to treatment if cancer develops.

OBJECTIVES: To assess the cost effectiveness from a Canadian perspective of index patient germline BRCA testing and then, if positive, family members with subsequent risk-reducing surgery (RRS) in as yet unaffected mutation carriers compared with no testing and treatment of cancer when it develops. METHODS: A patient level simulation was developed comparing outcomes between two groups using Canadian data. Group 1: no mutation testing with treatment if cancer developed. Group 2: cascade testing (index patient BRCA tested and first-/second-degree relatives tested if index patient/first-degree relative is positive) with RRS in carriers. End points were the incremental cost-effectiveness ratio (ICER) and budget impact. RESULTS: There were 29,102 index patients: 2,786 ovarian cancer and 26,316 breast cancer (BC). Using the base-case assumption of 44 percent and 21 percent of women with a BRCA mutation receiving risk-reducing bilateral salpingo-oophorectomy and risk-reducing mastectomy, respectively, testing was cost effective versus no testing and treatment on cancer development, with an ICER of CAD 14,942 (USD 10,555) per quality-adjusted life-year (QALY), 127 and 104 fewer cases of ovarian and BC, respectively, and twenty-one fewer all-cause deaths. Testing remained cost effective versus no testing at the commonly accepted North American threshold of approximately CAD 100,000 (or USD 100,000) per QALY gained in all scenario analyses, and cost effectiveness improved as RRS uptake rates increased. CONCLUSIONS: Prevention via testing and RRS is cost effective at current RRS uptake rates; however, optimization of uptake rates and RRS will increase cost effectiveness and can provide cost savings.

Single or two drug combination therapy as initial treatment for low risk, gestational trophoblastic neoplasia. A Canadian analysis.

INTRODUCTION: Low risk gestational trophoblastic neoplasia, WHO prognostic score of 0 to 6, is highly curable. There is no consensus on the optimal chemotherapy. Common regimens are q2wk actinomycin-D (ACT-D), weekly intramuscular methotrexate (MTX) or multi-day MTX. Combination MTX/ACT-D is rarely used. METHODS: A four centre, retrospective cohort study was carried out comparing commonly used regimens: weekly MTX, q2weekly ACT-D and q2 weekly MTX and ACT-D. RESULTS: 412 patients - 196 MTX/ACT-D, 107 MTX, 109 ACT-D - were treated between October 1994 and January 2019. Initial regimen failure (secondary to resistance or toxicity) occurred in 37% (MTX), 21% (ACT-D) and 5% (MTX/ACT-D). Relapse after completion of primary therapy (initial plus switch to another therapy if needed) was rare (0-5%). All eventually were cured. Mean number of cycles required to achieve remission were 10.1 (MTX), 7 (ACT-D) and 5.6 (MTX/ACT-D) with corresponding mean treatment durations of 3.12, 2.9 and 2.26 months. Dosage reductions occurred in 3% (MTX), 0% (ACT-D) and 29% (MTX/ACT-D). Higher failure rates occurred with WHO prognostic scores of 5 to 6 and HCG levels ≥10,000. SUMMARY: Initial regimen failure ie the need to switch to an alternative treatment was more common with MTX. ACT-D and MTX/ACT-D were similar within prognostic score 0-4 or HCG < 10,000. ACT-D then appears the better initial choice with its superior convenience. Above these levels primary failure rates are less with MTX/ACT-D, making it a better choice.

Low-grade serous carcinoma (LGSC): A Canadian multicenter review of practice patterns and patient outcomes.

OBJECTIVE: Patients with advanced low-grade serous carcinoma (LGSC) have poor long-term survival rates. As a rare histotype, there are uncertainties regarding the use of current therapies. Thus, we studied practice patterns and treatment outcomes as part of a national initiative to better understand and improve the care of women with advanced LGSC. METHODS: This retrospective cohort study was conducted in 5 Canadian referral institutions from 2000 to 2016. Data collection and pathology reporting were standardized. Outcome measures included overall survival (OS), progression-free survival (PFS), progression-free intervals (PFI), and time to next treatment (TTNT). Cox regression analysis was used to evaluate the effects of clinical and pathologic factors on outcomes and prognosis. RESULTS: There were 134 patients (stage II-IV) with a median follow-up of 32.4 months (range 1.6-228). Four primary treatments were compared across institutions: 1) surgery followed by chemotherapy (56%), 2) neoadjuvant chemotherapy (NACT) followed by surgery (27%), 3) surgery alone (9%), and 4) surgery followed by anti-hormone therapy (4%). Primary platinum/paclitaxel chemotherapy was used in 81%. Patients treated with NACT had worse PFS. Multivariable Cox regression analysis identified lesser residual disease, younger age, and primary peritoneal origin as variables significantly associated with better OS/PFS (p < 0.03). One institution had significantly better PFS than the others (p = 0.025), but this finding could be related to a higher frequency of primary peritoneal LGSC. PFI and TTNT intervals in patients with relapsed disease were not significantly different after the first relapse irrespective of treatment type. CONCLUSIONS: There are notable differences in practice patterns across Canada. This underscores the need for ongoing strategies to measure, evaluate and achieve optimal patient outcomes for women with advanced LGSC.

Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer.

BACKGROUND: Niraparib, an inhibitor of poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP), has been associated with significantly increased progression-free survival among patients with recurrent ovarian cancer after platinum-based chemotherapy, regardless of the presence or absence of BRCA mutations. The efficacy of niraparib in patients with newly diagnosed advanced ovarian cancer after a response to first-line platinum-based chemotherapy is unknown. METHODS: In this randomized, double-blind, phase 3 trial, we randomly assigned patients with newly diagnosed advanced ovarian cancer in a 2:1 ratio to receive niraparib or placebo once daily after a response to platinum-based chemotherapy. The primary end point was progression-free survival in patients who had tumors with homologous-recombination deficiency and in those in the overall population, as determined on hierarchical testing. A prespecified interim analysis for overall survival was conducted at the time of the primary analysis of progression-free survival. RESULTS: Of the 733 patients who underwent randomization, 373 (50.9%) had tumors with homologous-recombination deficiency. Among the patients in this category, the median progression-free survival was significantly longer in the niraparib group than in the placebo group (21.9 months vs. 10.4 months; hazard ratio for disease progression or death, 0.43; 95% confidence interval [CI], 0.31 to 0.59; P<0.001). In the overall population, the corresponding progression-free survival was 13.8 months and 8.2 months (hazard ratio, 0.62; 95% CI, 0.50 to 0.76; P<0.001). At the 24-month interim analysis, the rate of overall survival was 84% in the niraparib group and 77% in the placebo group (hazard ratio, 0.70; 95% CI, 0.44 to 1.11). The most common adverse events of grade 3 or higher were anemia (in 31.0% of the patients), thrombocytopenia (in 28.7%), and neutropenia (in 12.8%). No treatment-related deaths occurred. CONCLUSIONS: Among patients with newly diagnosed advanced ovarian cancer who had a response to platinum-based chemotherapy, those who received niraparib had significantly longer progression-free survival than those who received placebo, regardless of the presence or absence of homologous-recombination deficiency. (Funded by GlaxoSmithKline; PRIMA/ENGOT-OV26/GOG-3012 ClinicalTrials.gov number, NCT02655016.).

Targeted surgical prevention of epithelial ovarian cancer is cost effective and saves money in BRCA mutation carrying family members of women with epithelial ovarian cancer. A Canadian model.

OBJECTIVE: Survival but not cure rates have improved for epithelial ovarian cancer (EOC), demonstrating the need for effective prevention. Targeted prevention in BRCA carriers by risk reducing surgery (RRS) prevents 80% of cases but incurs additional up-front costs, compensated for by the potential for long term savings from treatment avoidance. Does prevention represent value for money? In the absence of long-term data from prospective trials, determining the cost effectiveness of a prevention strategy requires economic modelling. METHODS: A patient level simulation was developed comparing outcomes between two groups, using Canadian data. Group 1: no mutation testing with treatment if EOC developed. Group 2: cascade testing (index patient BRCA tested and the first and second-degree relatives tested if index patient or first-degree relative respectively were positive) with RRS in carriers. End points were Incremental Cost-Effectiveness Ratio (ICER) and budget impact. RESULTS: 2786 women with EOC (1 year incidence) had 766 first and 207 second-degree female relatives. BRCA mutations were present in 390 index cases, 366 first and 49 second-degree relatives. With 100% RRS uptake, 59 EOC were prevented and testing dominated no testing (more effective and less costly; ICER -$8919). The total cost saving over 50 years was $2,904,486 (cost saving of $9,660,381 in treatment costs versus increased cost from cascade testing/RRS of $6,755,895). At a threshold of $100,000 per QALY, prevention was cost effective in all modelled scenarios. CONCLUSIONS: Targeted prevention in BRCA mutation carriers not only prevents EOC but is cost-effective compared to treating EOC if it develops.

Evolution of genetic assessment for BRCA-associated gynaecologic malignancies: a Canadian multisociety roadmap.

The landscape of genetic testing in ovarian cancer patients has changed dramatically in recent years. The therapeutic benefits of poly ADP-ribose polymerase (PARP) inhibitors in treatment of BRCA1/2-related ovarian cancers has resulted in an increased demand and urgency for genetic testing results, while technological developments have led to widespread use of multi-gene cancer panels and development of tumour testing protocols. Traditional genetic counselling models are no longer sustainable and must evolve to match the rapid evolution of genetic testing technologies and developments in personalized medicine. Recently, representatives from oncology, clinical genetics, molecular genetics, pathology, and patient advocacy came together to create a national multi-disciplinary Canadian consortium. By aligning stakeholder interests, the BRCA Testing to Treatment (BRCA TtoT) Community of Practice aims to develop a national strategy for tumour and germline BRCA1/2 testing and genetic counselling in women with ovarian cancer. This article serves to provide an overview of the recent evolution of genetic assessment for BRCA1/2-associated gynecologic malignancies and outline a Canadian roadmap to facilitate change, improve genetic testing rates, and ultimately improve outcomes for hereditary ovarian cancer patients and their families.

Chemotherapy is of Value in Second Line and Beyond, Relapsed High-grade, Serous Epithelial Ovarian Cancer: An Analysis of Outcomes Obtained With Oral Etoposide.

BACKGROUND: Epithelial ovarian cancer is chemotherapy responsive, and multiple lines of chemotherapy are often given. However, there are few data with regard to its effectiveness in later lines. Our aim was to assess its benefit in the high-grade, serous subtype relative to the line of therapy, using etoposide as the example. METHODS: Women treated with oral etoposide at the British Columbia Cancer Agency upon recurrence/progression in the years 2000 to 2010 were reviewed. Kaplan-Meier and Cox regression methods were used to correlate line of therapy with overall survival, progression-free survival, and interval between etoposide initiation and next progression or death (EPFS). RESULTS: A total of 219 women, median age 61, received etoposide as second (17%), third (30%), fourth (26%), fifth (17%), and sixth to eighth (11%) lines of therapy. The median number of cycles was 2 to 4. Patients who received etoposide as fourth-line to eighth-line treatment had a significantly longer median overall survival and initial progression-free survival (from diagnosis to first relapse) when compared with those who received it as second-line to third-line treatment (47.8 vs. 25.8 mo, P<0.0001; and 16.1 vs. 12.1 mo, P<0.0001, respectively); that is, a selected population of survivors received it later in the course of their disease. On univariate analysis, there was no significant difference in median EPFS (range, 2 to 2.9 mo) on the basis of line of therapy. On multivariate analysis, the hazard ratios improved through the third, fourth, and fifth lines (hazard ratios: 0.82, 0.77, and 0.34, respectively), and was statistically significant in the fifth line. The a priori-defined endpoint of clinical benefit was the "percentage not progressing at 3 months," and this was achieved in 32% to 48%. CONCLUSIONS: In this retrospective study, a similar degree of benefit from etoposide, as defined by the percentage remaining progression free at 3 months, was seen in all lines of therapy.

Survival Benefit of Adjuvant Radiotherapy: An Analysis of Low-Stage Invasive Ovarian Mucinous Carcinomas.

OBJECTIVE: Our aim was to evaluate the population-based outcomes of stages I and II invasive ovarian mucinous carcinomas (MCs) treated with adjuvant platinum-based chemotherapy and abdominopelvic radiotherapy (XRT). METHODS: International Federation of Gynecology and Obstetrics stage I/II MC cases referred to the British Columbia Cancer Agency between 1984 and 2014 were reviewed. Chemotherapy (minimum of 3 cycles) and XRT were the institutional policy for stages IA/B (grade 2/3) and IC/II (any grade). Physician patterns of practice determined XRT use in eligible patients, allowing for the comparison of outcomes based on receipt of XRT treatment on disease-free survival (DFS) and overall survival (OS). RESULTS: We identified 129 patients. Univariate analyses on substages IA, IC no rupture, IC with intraoperative rupture, and IC with preoperative rupture demonstrated 10-year DFS rates of 67%, 67%, 67%, and 27% (P = 0.004), respectively, and OS rates of 72%, 72%, 67%, and 38% (P = 0.01), respectively. For all patients, adjuvant XRT demonstrated improved 10-year DFS (78% vs 36%, P = 0.05) and OS (83% vs 36%, P = 0.02). Subgroup analysis did not detect a benefit of adjuvant therapy for stage IA grade 1/2. Multivariate analysis confirmed the benefit of XRT on DFS (hazard ratio, 0.14; 95% confidence interval, 0.02-0.98; P = 0.047) and a trend to improved OS (hazard ratio, 0.12; 95% confidence interval, 0.009-1.64; P = 0.11), whereas decision tree analysis demonstrated a reduced rate of relapse (33% vs 77%) and death (20% vs 46%) with the use of XRT, exclusive of patients with preoperative rupture. CONCLUSIONS: This population-based retrospective study is the first to demonstrate that the use of adjuvant abdominopelvic XRT after chemotherapy can improve survival in patients diagnosed as having stage I/II MC. Patients with stage IA grade 1 and grade 2 MC can have adjuvant therapy omitted.

Missed therapeutic and prevention opportunities in women with BRCA-mutated epithelial ovarian cancer and their families due to low referral rates for genetic counseling and BRCA testing: A review of the literature.

Answer questions and earn CME/CNE Fifteen percent of women with epithelial ovarian cancer have inherited mutations in the BRCA breast cancer susceptibility genes. Knowledge of her BRCA status has value both for the woman and for her family. A therapeutic benefit exists for the woman with cancer, because a new family of oral drugs, the poly ADP-ribose polymerase (PARP) inhibitors, has recently been approved, and these drugs have the greatest efficacy in women who carry the mutation. For her family, there is the potential to prevent ovarian cancer in those carrying the mutation by using risk-reducing surgery. Such surgery significantly reduces the chance of developing this, for the most part, incurable cancer. Despite these potential benefits, referral rates for genetic counseling and subsequent BRCA testing are low, ranging from 10% to 30%, indicating that these therapeutic and prevention opportunities are being missed. The authors have reviewed the relevant available literature. Topics discussed are BRCA and its relation to ovarian cancer, the rates of referral for genetic counseling/BRCA testing, reasons for these low rates, potential strategies to improve on those rates, lack of effectiveness of current screening strategies, the pros and cons of risk-reducing surgery, other prevention options, and the role and value of PARP inhibitors. CA Cancer J Clin 2017;67:493-506. © 2017 American Cancer Society.

Gemcitabine, dexamethasone, and cisplatin (GDP) is an effective and well-tolerated salvage therapy for relapsed/refractory diffuse large B-cell lymphoma and Hodgkin lymphoma.

The optimal choice of salvage therapy for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma (HL) remains unknown. Based on promising results of phase II trials, the preferred salvage regimen in British Columbia since 2002 has been the out-patient regimen, gemcitabine, dexamethasone, and cisplatin (GDP). We conducted a retrospective analysis including all patients with relapsed/refractory DLBCL or HL who received GDP as salvage therapy between September 2002 and June 2010. We identified 235 patients: 152 DLBCL, 83 HL. Overall response rates were 49% and 71% for patients with DLBCL and HL, respectively. Within the transplant-eligible population, 52% of patients with DLBCL and 96% of patients with HL proceeded to stem cell transplantation. The 2-year progression-free survival and overall survival were 21% and 28% in the DLBCL cohort, and 58% and 85% in the HL group. GDP is an effective and well-tolerated out-patient salvage regimen for relapsed/refractory DLBCL and HL.

Randomized study of sequential cisplatin-topotecan/carboplatin-paclitaxel versus carboplatin-paclitaxel: effects on quality of life.

BACKGROUND: A recent phase III trial compared the efficacy of cisplatin-topotecan (a topoisomerase I inhibitor) followed by carboplatin-paclitaxel (Arm 1) versus paclitaxel-carboplatin (Arm 2) in women with newly diagnosed stage IIB or greater ovarian cancer. There was a significantly lower response rate in the experimental arm compared to standard treatment, and less likelihood of normalized CA125 within the first 3 months. At 43 months follow-up, there were no significant group differences in progression-free survival. There were also significantly more side effects in the experimental arm. METHODS: The current study examined quality of life (QoL) endpoints using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and the ovarian cancer module, QLQ-OV28, administered prior to randomization, at day 1 of treatment cycles 3, 5, and 7, at completion of the last cycle, and at 3 and 6 months following completion of chemotherapy. RESULTS: Global QoL, physical symptoms, fatigue, and role, emotional, cognitive and social function (all from the EORTC QLQ-C30) significantly improved in both treatment arms, with no significant between-arm differences. Between-group differences in pain, insomnia, and peripheral neuropathy reported while on treatment did not differ at follow-up. Nausea and vomiting improved more with standard treatment both during and after treatment. Body image significantly differed between the groups only at cycle 5 (more deterioration in Arm 2) but group differences disappeared at follow-up. A stratified analysis of global QoL by debulking surgery status found no greater effect indicating that overall improvements in QoL were unrelated to surgical recovery. CONCLUSIONS: There was no significant QoL advantage of cisplatin-topotecan. This finding, combined with no progression-free survival conferred by this combination, reaffirms carboplatin-paclitaxel as the standard of care for women with newly diagnosed ovarian cancer.

Early-stage endometrioid ovarian carcinoma: population-based outcomes in British Columbia.

OBJECTIVE: Specific outcomes for early-stage ovarian endometrioid carcinoma (OEC) have not been well characterized. In addition, the benefit of any type of postsurgical therapy remains unclear. Our aims were to delineate (1) potential prognostic factors and (2) the impact of adjuvant treatment on survival in such patients. METHODS: Women with FIGO stages I and II OEC referred to one of the centers of the British Columbia Cancer Agency from 1984 to 2008 were included in a retrospectively abstracted computerized database. Irradiation (abdominal-pelvic) in addition to chemotherapy (3 cycles of platinum combination) was to be given for stage IA/B, grade 2/3; stage IC, any grade; and stage II, any grade, except from 1989 to 1994 when irradiation was dropped from the paradigm for all patients. Univariate analysis and a multivariate analysis, using a decision tree analysis, were carried out of disease-free survival (DFS). RESULTS: One hundred seventy-two patients were identified. Twelve percent were grade 3; 55%, 85%, and 89% of stages IA/B, IC, and II received postoperative adjuvant treatment. Five-year DFS was 95%, 84%, and 74% for stages IA/B and IC based upon rupture alone, IC other (cytologic positivity and/or surface involvement), and II, respectively. No benefit in DFS was accrued in stage IA/B from adjuvant treatment. Decision tree analysis defined 2 poor prognostic groups: those 55 years or older with stage IC based upon positive washings or surface involvement and any patient with stage II disease; in these, an apparent DFS benefit from irradiation was seen (relative risk (RR), 1.77; 95% confidence interval (CI), 0.74-4.24). CONCLUSION: Omission of adjuvant treatment can be considered in most early-stage OECs.

Population-based treatment and outcomes of Stage I uterine serous carcinoma.

OBJECTIVE: Uterine serous carcinoma (USC) is a rare type of endometrial cancer that often recurs in patients with Stage I disease. Our objective was to evaluate treatment and outcomes in Stage I USC in the context of a population-based study. METHODS: This was a population-based retrospective cohort study of all patients with Stage I USC in British Columbia, Canada from 2004 to 2012. The British Columbia Cancer Agency (BCCA) recommends three cycles of paclitaxel and carboplatin chemotherapy followed by pelvic radiotherapy for all women with Stage I USC and any myometrial invasion (Stage IA MI-). If no myometrial invasion (Stage IA MI-), no postoperative treatment is given. Patient and disease characteristics, surgery, adjuvant therapy, recurrence rates and sites, and 5-year disease-free survival rates were evaluated. RESULTS: Of the 127 patients with Stage I USC, 41 were Stage IA MI-, 56 Stage IA MI+, and 30 Stage IB. Median follow-up was 25 months (2-98 months). Five year disease-free survival rates were 80.7%, 74.4%, and 48.5% for Stages IA MI-, IA MI+, and IB, respectively, and recurrence rates according to BCCA guidelines were 10%, 2.9% and 30%, respectively. Of the 18 with recurrences, 13 had a distant component (72.2%). There were no pelvic recurrences among those receiving adjuvant radiotherapy. CONCLUSION: Our current protocol of observation alone postoperatively for Stage IA MI- and chemoradiotherapy for Stage IA MI+ is associated with a low recurrence rate. In contrast, those with Stage IB USC have a higher recurrence rate despite chemoradiotherapy, and likely require alternate treatment strategies.

The importance of adjuvant chemotherapy and pelvic radiotherapy in high-risk early stage endometrial carcinoma.

OBJECTIVE: To determine the impact of a policy change in which women with high-risk early stage endometrioid endometrial cancer (EEC) received adjuvant chemoradiotherapy. METHODS: This is a population-based retrospective cohort study of British Columbia Cancer Registry patients diagnosed from 2008 to 2012 with high-risk early stage EEC, who received adjuvant chemoradiotherapy after primary surgery. High-risk early stage was defined as the presence of two or more high-risk uterine factors: grade 3 tumor, more than 50% myometrial invasion, and/or cervical stromal involvement. Adjuvant therapy consisted of 3 or 4 cycles of carboplatin and paclitaxel chemotherapy, followed by pelvic radiotherapy. Sites and rate of recurrence were compared to a historical cohort diagnosed from 2005 to 2008 in which none of the patients received adjuvant chemoradiotherapy. Five-year progression-free and overall survival rates were calculated. RESULTS: The study includes 55 patients. All patients except for 2 received at least 3 cycles of chemotherapy. All patients received pelvic radiotherapy except for 2 who received brachytherapy only. Median follow-up was 27 months (7-56 months). Four patients (7.3%) recurred, including three with distant recurrence only and one with both a pelvic and paraaortic nodal recurrence. The historical cohort had a 29.4% recurrence rate, and therefore the hazard ratio for recurrence was 0.27 (95% CI 0.02-4.11). Five-year progression-free and overall survival rates were 88.6% and 97.3%, respectively. CONCLUSION: Patients with high-risk early stage endometrial carcinoma treated with adjuvant chemoradiotherapy have a low rate of recurrence compared to those not receiving such therapy.