Malakoplakia of the Endometrium: A Rare Unexpected Disease Raising Clinical Concern for Malignancy.

Malakoplakia is a rare disease that manifests as a histiocytic inflammatory process and most often occurs in the urinary bladder. It is caused by an impaired capacity of histiocytes to kill and digest bacteria. The typical histopathologic findings are sheets of histiocytes with granular eosinophilic cytoplasm and characteristic Michaelis-Gutmann bodies, spherical bodies with a targetoid appearance. Malakoplakia is even rarer in the gynecologic tract, and our literature search found only 21 published patients of malakoplakia involving the endometrium. Here we report a 60-year-old female patient who presented with recurrent pelvic infections and postmenopausal bleeding, which raised concern for an endometrial malignancy. Hysterectomy with salpingo-oophorectomy revealed malakoplakia involving the endometrium and also the right ovary. Michaelis-Gutmann bodies were visible on the intraoperative frozen section that was performed to rule out an endometrial malignancy. We summarize the clinicopathologic findings of the published patients of endometrial malakoplakia.

Improving Sexual and Gender Minority Cancer Care: Patient and Caregiver Perspectives From a Multi-Methods Pilot Study.

Purpose: Up to 1 million lesbian, gay, bisexual, and transgender (i.e., sexual and gender minority, SGM) individuals in the United States have histories of cancer. This medically underserved population is diverse, with complex sexualities and gender identities, and distinct health concerns. SGM persons experience disproportionate risks for, and rates of, anal, breast, cervical, colorectal, endometrial, lung, and prostate cancers, in addition to cancers affecting transgender persons who have undergone sex-reassignment. SGM individuals are linked by shared experiences of stigmatization as a minority population for which little cancer research has been conducted. SGM cancer patients frequently report reluctance to seek healthcare, have poorer outcomes following diagnosis, engage in elevated risk behaviors (i.e. smoking and alcohol use) even after cancer diagnosis, have difficulty making emotional adjustment to illness, and experience higher rates of psychological distress. They report less satisfaction with cancer care, deficiencies in patient-centeredness and shared decision-making, gaps in care, and social isolation. Minority stress resulting from experiences of anti-SGM sentiment and discrimination affects cancer patients and their informal cancer caregivers. Our paper presents findings from a pilot study to identify gaps and opportunities to improve cancer care for SGM patients and caregivers at the University of New Mexico Comprehensive Cancer Center. Methods: Between June 2020 and July 2021, we used a multi-methods research design informed by ecological theory to collect qualitative and quantitative data regarding cancer patient and caregiver quality of life (QoL) and experiences of cancer and survivorship care. We used PROMIS measures distributed via REDCap to assess QoL (i.e., fatigue, pain interference, pain intensity, anxiety, depression, emotional support, social isolation, and companionship), and conducted in-depth semi-structured interviews. We recruited 10 SGM cancer patients and 8 heterosexual, cisgender (H/C) patient matches, and their self-identified informal cancer caregivers (n=36, dyad total n=18). Interviews ranged from 1 to 2 hours, were audio-recorded and transcribed for analysis. The study was approved by the University of New Mexico Human Research Protections Office Institutional Review Board. Results: Results of the PROMIS QoL assessments indicated that SGM patients reported greater anxiety [mean (SD) = 54.5 (8.8)] and depression [mean (SD) = 49.3 (4.8)] than H/C patients [mean (SD)=51.6 (7.5) and 45.4 (6.8) respectively], while heterosexual, cisgender (H/C) patients reported higher fatigue [mean (SD) =52.04 (8.18)] and stronger pain intensity than SGM patients [mean (SD)=48.3 (9.1) and 37.8 (9.1) respectively]. SGM patients reported higher levels of social isolation [mean (SD) = 48.3 (7.3) vs. 42.1 (7.4) for H/C patients, whereas H/C patients reported more emotional support (mean (SD) =57.5 (9.3) vs. 53.0 (6.9)] and companionship [mean (SD) = 55.2 (8.6) vs. 51.5 (11.0)]. SGM and H/C differences in caregiver QoL were most notable with regards to higher levels of fatigue [mean (SD) = 47.1 (6.0) for SGM, and 42.4 (11.5) for H/C] and companionship [mean (SD) = 55.3 (6.0) for SGM, and 50.9 (5.5) for H/C]. Qualitative interviews supported our quantitative results. SGM patients and caregivers articulated experiences of anti-SGM stigma and discrimination contributing to minority stress that influenced their initial cancer care encounters. SGM dyads had more trepidation and/or medical mistrust during initial cancer care encounters when compared to H/C patients and caregivers. SGM patients questioned care that was not culturally responsive to SGM preferences, while H/C patients were more apt to identify gaps in communication and perceived lack of clarity regarding cancer care delivery. Although SGM patients experienced high satisfaction with their cancer care once they developed trust with their providers, they discussed desires to have more direct conversations with their oncologists about their sexual orientation and gender identities and sexual health. All patients and providers in the study (SGM and H/C) appreciated their oncology care teams. All patients and caregivers relied on social networks comprised of friends and family, although SGM patients and caregivers had smaller social networks and relied less on biological family, and single SGM individuals experienced challenges accessing cancer care and struggled with social isolation. We discovered too, that all caregivers, regardless of Sexual Orientation and Gender Identity (SOGI), perceived a lack of support and information pertaining to their loved one's treatment, side effects and best way to provide care. Conclusions: This study demonstrates that prior stigmatizing experiences contribute to minority stress and medical mistrust for SGM cancer patients and their informal caregivers across the cancer care experience. Findings point to specific gaps in SGM cancer patient care, including lack of conversation about patient SOGI, inadequate staff and oncology provider SGM specific knowledge and cultural competence/cultural humility training, and insufficient patient supports for those who lack social support during cancer care treatment. Further, this study reveals inadequacies in SGM specific support, and overall support services for informal cancer caregivers. Additional research is required to develop targeted interventions to address minority stress and clinic environment concerns to improve cancer care for SGM patients. Importantly, while there were differences between SGM and H/C experiences of cancer treatment, significant similarities also emerged. Caregiver expressed consensus about the current lack of support and guidance for informal caregivers of cancer patients. Future work should focus on providing caregiver-specific resources in the clinic setting and facilitating support groups for caregivers to network with one another, as well as for tailoring SGM specific caregiver support services. Our findings highlight areas for improving cancer care for the SGM community, as well as a broader population of patients and caregivers.

Characterizing Low-Risk Breast and Gynecological Cancer Patients for Transition into an Oncology/Primary Care Coordinated Care Model: Findings from a Survey of Diverse Survivors in a Rural U.S. State.

We conducted a survey to characterize the key attributes of racial/ethnic and geographically diverse low-risk breast and gynecologic cancer patients. We collected data regarding patients' access to primary care (PC); compliance with screening recommendations; treatment for comorbidities; logistical barriers to clinic visits; and receipt of survivorship care documentation (SCD). Survey findings informed the development of an oncology/Primary Care Provider (PCP) care coordination intervention to improve care. We distributed a cross-sectional survey among a convenience sample of 150 cancer survivors. Responses were calculated using descriptive statistics and compared based on the distance participants traveled to their appointments at the cancer center (≤30 vs. >30 miles). Of the 150 respondents, 35% traveled >30 miles for follow-up care and 78% reported having one or more comorbid condition(s). PC utilization was high: 88% reported having a PCP, and 91% indicated ≤1 yearly follow-up visit. Participants traveling >30 miles reported higher rates of logistical challenges associated with cancer center visits compared to those traveling ≤30 miles. Nearly half of respondents (46%) had not received SCD. In conclusion, survey studies such as these allow for the systematic assessment of survivor behaviors and care utilization patterns to inform the development of care coordination interventions for diverse, low-risk cancer patients.

Randomized phase IIB evaluation of weekly paclitaxel versus weekly paclitaxel with oncolytic reovirus (Reolysin®) in recurrent ovarian, tubal, or peritoneal cancer: An NRG Oncology/Gynecologic Oncology Group study.

OBJECTIVE: To assess whether the addition of oncolytic reovirus (Reolysin®) to weekly paclitaxel prolonged progression-free survival (PFS) in the treatment of women with recurrent or persistent ovarian, tubal or primary peritoneal cancer. PATIENTS AND METHODS: Patients with recurrent or persistent epithelial ovarian, tubal, or peritoneal carcinoma, measurable or detectable disease, and three or fewer prior regimens were randomly assigned to paclitaxel (80mg/m2 intravenously days 1, 8, and 15 every 4weeks) or the combination of paclitaxel (80mg/m2 intravenously days 1, 8, and 15) plus reovirus 3×1010TCID50/day intravenously on days 1-5, both every 4weeks until disease progression or toxicity. The primary end point was PFS. The study was designed with 80% power for a one-sided alternative at a 10% level of significance to detect a reduction in the hazard by 37.5%. RESULTS: The study accrued 108 patients, 100 of whom were evaluable for toxicity. Median PFS was 4.3months for paclitaxel and 4.4months for paclitaxel plus reovirus (hazard ratio, 1.11; 90% two-sided CI, 0.78 to 1.59; one-sided P=0.687). The proportion responding (overall response rate) to paclitaxel was 20% among 45 patients with measurable disease receiving paclitaxel alone, and 17.4% among the 46 patients treated with the combination. The asymptotic relative probability of responding was 0.87 (90% CI, 0.42 to 1.79). Severe adverse events were more common in the combination regimen than in paclitaxel arm for severe neutropenia (grade≥4, 12% versus 0%), and severe respiratory adverse events (grade≥3, 25% versus 2%). No deaths were considered treatment related. CONCLUSION: The addition of reovirus to weekly paclitaxel in the treatment of women with recurrent or persistent ovarian, tubal or peritoneal cancer did not sufficiently reduce the hazard of progression or death to warrant further investigation.

Optimizing endometrial cancer follow-up and survivorship care for rural and other underserved women: Patient and provider perspectives.

OBJECTIVES: This study describes patient and provider attitudes on transitioning cancer surveillance visits and treatment of comorbid conditions to the primary care setting in a rural patient population as a strategy for minimizing financial and travel related barriers for patients while simultaneously enhancing quality and availability of health care options. METHODS: Focus group discussions and telephone interviews were conducted with endometrial cancer (EC) survivors and primary care providers (PCPs) to provide insights into post-treatment follow-up practices and the acceptability of transitioning follow-up to primary care setting utilizing a cancer survivorship care plan model. RESULTS: EC survivors expressed high levels of satisfaction with their oncology care and suggested that transitioning to PCPs for follow-up care would be convenient yet challenging. Challenges cited include: 1) patient perceptions of deficits in PCP's understandings of cancer surveillance; 2) inability to identify a personal PCP; and 3) lack of communication between oncologists and PCPs. PCP participants similarly identified the need for extensive EC training and effective communication strategies with oncologists as necessary factors for accepting responsibility for EC follow-up care. Both groups offered strategies to create a more team based approach to EC survivorship care. CONCLUSIONS: Increasing the role of the PCP in the ongoing care of EC survivors was generally considered acceptable by both patients and providers in both rural and urban women. Successful coordination of care between cancer survivors, oncologists and PCPs will be a critical step in improving the cancer care delivery of our rural patient and provider population.

A pilot randomized control trial to evaluate pelvic floor muscle training for urinary incontinence among gynecologic cancer survivors.

OBJECTIVES: We previously reported high rates of urinary incontinence among gynecologic cancer survivors and aimed to evaluate the effectiveness of a simple intervention for treatment of urinary incontinence in this population. METHODS: We recruited 40 gynecologic cancer survivors who reported urinary incontinence on a validated questionnaire. Women were randomized to either pelvic floor muscle training/behavioral therapy (treatment group) or usual care (control group). The primary outcome measure, assessed at 12 weeks post intervention, was a 40% difference in the validated Patient Global Impression of Improvement (PGI-I) score. Fisher's exact test was used to identify differences between groups for frequency data; two-sample t-test was conducted for continuous measurements. RESULTS: Mean age of this cohort was 57 (range: 37-79). The majority of the survivors had uterine cancer (60%), 18% had received radiation therapy, 95% had received surgical therapy, and 35% had received chemotherapy. At three months, 80% of the treatment and 40% of the control group reported that their urinary incontinence was "much better" or "very much better" as evaluated by the Patient Global Impression of Improvement scale (p=0.02). Brink's scores were significantly improved in the treatment group as compared to those of the controls (p<0.0001). Treatment group adherence was high; the treatment group performed exercises with an average of 22 days/month. CONCLUSIONS: Urinary incontinence negatively affects quality of life, and despite a high prevalence among gynecologic cancer survivors, it is often under-assessed and undertreated. We found a simple intervention that included pelvic floor muscle training and behavioral therapy, which significantly improved cancer survivor's urinary incontinence.

Advances in surgical care.

The numerous advances in the surgical care of gynecologic oncology patients are allowing clinicians to offer improved quality of life while maintaining excellent cancer outcomes. Advances in technology and disease understanding will only enhance our surgical abilities beyond what can be imagined today. Surgeons have a responsibility to evaluate new technology critically and incorporate the technology into patient care safely and efficiently.

Promotion rates for assistant and associate professors in obstetrics and gynecology.

OBJECTIVE: To estimate promotion rates of physician faculty members in obstetrics and gynecology during the past 30 years METHODS: Data were collected annually by the Association of American Medical Colleges from every school between 1980 and 2009 for first-time assistant and associate professors to determine whether and when they were promoted. Data for full-time physician faculty were aggregated by decade (1980-1989, 1990-1999, 2000-2009). Faculty were included if they remained in academia for 10 years after beginning in rank. Data were analyzed by constructing estimated promotion curves and extracting 6-year and 10-year promotion rates. RESULTS: The 10-year promotion rates (adjusted for attrition) declined significantly for assistant professors from 35% in 1980-1989 to 32% in 1990-1999 to 26% in 2000-2009 (P<.001), and for associate professors from 37% to 32% to 26%, respectively (P<.005). These declines most likely resulted from changes in faculty composition. The most recent 15 years saw a steady increase in the proportion of entry-level faculty who were women (now 2:1) and primarily on the nontenure track. The increasing number of faculty in general obstetrics and gynecology had lower promotion probabilities than those in the subspecialties (odds ratio 0.16; P<.001). Female faculty on the nontenure track had lower promotion rates than males on the nontenure track, males on the tenure track, and females on the tenure track (odds ratio 0.8 or less; P<.01). CONCLUSION: A decline in promotion rates during the past 30 years may be attributable to changes in faculty composition. LEVEL OF EVIDENCE: II.

Pelvic floor disorders and sexual function in gynecologic cancer survivors: a cohort study.

OBJECTIVE: The purpose of this study was to assess the prevalence of pelvic floor disorders and sexual function in survivors of gynecologic cancer. STUDY DESIGN: We surveyed survivors of gynecologic cancer (survivors) and women seeking gynecologic care (control patients) who were >30 years old. All survivors were disease- and treatment-free for ≥1 year. Validated questionnaires were used to evaluate pelvic floor disorders. RESULTS: One hundred eight control patient and 260 survivor questionnaires were completed. A high prevalence of pelvic floor disorders was observed in both groups; 56% of control subjects and 70% of survivors reported moderate to severe urinary incontinence (P > .05). Survivors were more likely to experience fecal incontinence (42% vs 32%; P = .02). Survivors reported less sexual desire (P = .04) and less ability to climax (P = .04), despite no difference in dyspareunia. CONCLUSION: Fecal incontinence and sexual dysfunction are significant problems in survivors of gynecologic cancer.

Uterine leiomyoma with associated pseudo-Meigs syndrome mimicking ovarian carcinoma.

BACKGROUND: Uterine leiomyoma are commonly diagnosed in women of reproductive age. However, these benign tumors may present with clinical signs and symptoms that are consistent with ovarian carcinoma. CASE: A 47-year-old gravida 0 presented with a large pelvic mass, ascites, bilateral pleural effusions, and an elevated CA 125 worrisome for ovarian carcinoma. Exploratory laparotomy revealed a 20,120 g pelvic mass, with 2 L ascites, and pelvic and periaortic lymphadenopathy. Final pathology was consistent with a benign giant leiomyoma. Postoperative course was complicated by reaccumulation of pleural effusion requiring therapeutic thoracentesis and diuretics. Patient had return to full activity with 50 pound weight loss at 8 weeks after surgery. CONCLUSION: Elevated CA 125 levels and ascites are often associated with ovarian carcinoma, but it is also important to keep benign processes in the differential diagnosis when considering malignancy.

The role of multi-modality adjuvant chemotherapy and radiation in women with advanced stage endometrial cancer.

OBJECTIVE: : The optimal adjuvant therapy for women with stages III and IV endometrial cancer following surgical staging and cytoreductive surgery is controversial. We sought to determine the outcome of patients with advanced stage endometrial cancer treated with postoperative chemotherapy+/-radiation to determine whether there was an advantage to combining treatment modalities. METHODS: : A retrospective analysis of patients with surgical stages III and IV endometrial cancer from 1975 to 2006 was conducted at Duke University and the University of North Carolina. Inclusion criteria were comprehensive staging procedure including hysterectomy, bilateral salpingo-oophorectomy, +/-selective pelvic/aortic lymphadenectomy, surgical debulking, and treatment with adjuvant chemotherapy and/or radiotherapy. Progression-free (PFS) and overall survival (OS) were analyzed using Kaplan-Meier method and Cox proportional hazards model. RESULTS: : 356 Patients with advanced stage endometrial cancer were identified who received postoperative adjuvant therapies; 48% (n=171) radiotherapy alone, 29% (n=102) chemotherapy alone, 23% (n=83) chemotherapy and radiation. The median age was 66 years; 38% had endometrioid tumors; and 83% were optimally debulked. There was a significant difference between the adjuvant treatment groups for both OS and PFS (p<0.001), with those receiving chemotherapy alone having poorer 3-year OS (33%) and PFS (19%) compared to either radiotherapy alone (70% and 59%) or combination therapy (79% and 62%). After adjusting for stage, age, grade, and debulking status the hazard ratio (HR) for OS was 1.60 (95% CI, 0.88 to 2.89; p=0.122) for chemotherapy alone and 2.01 (95% CI, 1.17 to 3.48; p=0.012) for radiotherapy alone, compared to combination therapy. When the analysis was restricted to optimally debulked patients the adjusted HR for patients who were treated with either chemotherapy or radiation alone indicated a significantly higher risk for disease progression [HR=1.84 (95% CI, 1.03 to 3.27; p=0.038); HR=1.80 (95% CI, 1.10 to 2.95; p=0.020)] and death [HR=2.33 (95% CI, 1.12 to 4.86; p=0.024); HR=2.64 (95% CI, 1.38 to 5.07; p=0.004)], respectively, compared to patients who received combination therapy. CONCLUSION: : Combined adjuvant chemotherapy and radiation was associated with improved survival in patients with advanced stage disease compared to either modality alone. Future clinical trials are needed to prospectively evaluate multi-modality adjuvant therapy in women with advanced staged endometrial cancer to determine the appropriate sequencing and types of chemotherapy and radiation.

Carcinosarcoma of the ovary-a case series.

OBJECTIVE: To evaluate our experience with ovarian carcinosarcoma and identify prognostic factors. METHODS: Thirty-one cases of ovarian carcinosarcoma were identified over a 6-year time period through tumor registry and pathology records. Fisher exact test and log rank using Kaplan-Meier method (P < 0.05) were used to compare variables with outcome. RESULTS: All 31 patients underwent initial surgical treatment with an appropriate staging procedure. Stage distribution: 1 stage I, 6 stage II, 23 stage III, and 1 stage IV. The median follow-up was 28 months. The median survival for the entire group was 21 months. Early vs. advanced stage significantly influenced progression-free interval, P = 0.05. Nineteen patients were found to have stage IIIC disease and required debulking procedures. In patients with stage IIIC disease, presence of residual disease was associated with decreased overall survival, P = 0.03. 29 patients received adjuvant chemotherapy with 11 patients receiving ifosfamide/cisplatin and 16 patients receiving carboplatin/taxol. Progression-free interval was improved with the use of ifosfamide/cisplatin vs. carboplatin/taxol. The median PFI was 12 months in the carbo/taxol group and has not been reached in the ifos/cisplatin group (P = 0.005). The overall survival was also significantly improved with the use of ifosfamide/cisplatin, P = 0.03. In advanced stage patients, overall survival was not significantly influenced by type of adjuvant chemotherapy administered, P = 0.13. CONCLUSIONS: Ovarian carcinosarcoma has a poor overall prognosis with median survival rates reported in the literature ranging from 7-10 months. Our series, although limited by a small number of patients, exhibits a more encouraging median survival of 21 months for the overall group. Aggressive debulking to eliminate residual disease and the use of ifosfamide/cisplatin chemotherapy seem to be factors in this improved outcome.

Flexible heteroarotinoids (Flex-Hets) exhibit improved therapeutic ratios as anti-cancer agents over retinoic acid receptor agonists.

The anti-cancer activities and toxicities of retinoic acid (RA) and synthetic retinoids are mediated through nuclear RA receptors (RARs) and retinoid X receptors (RXRs) that act as transcription factors. Heteroarotinoids (Hets), which contain a heteroatom in the cyclic ring of an arotinoid structure, exhibit similar anti-cancer activities, but reduced toxicity in vivo, in comparison to parent retinoids and RA. A new class of Flexible Hets (Flex-Hets), which contain 3-atom urea or thiourea linkers, regulate growth and differentiation similar to RA, but do not activate RARs or RXRs. In addition, Flex-Hets induce potent apoptosis in ovarian cancer and in head and neck cancer cell lines through the intrinsic mitochondrial pathway. In this study, 4 cervical cancer cell lines were growth inhibited by micromolar concentrations of Flex-Hets to greater extents than RAR/RXR active retinoids. The most potent Flex-Het (SHetA2) inhibited each cell line of the National Cancer Institute's human tumor cell line panel at micromolar concentrations. Oral administration of Flex-Hets (SHetA2 and SHetA4) inhibited growth of OVCAR-3 ovarian cancer xenografts to similar extents as administration of a RAR/RXR-panagonist (SHet50) and Fenretinide (4-HPR) in vivo. None of these compounds induced evidence of skin, bone or liver toxicity, or increased levels of serum alanine aminotransferase (ALT) in the treated mice. Topical application of Flex-Hets did not induce skin irritation in vivo, whereas a RAR/RXR-panagonist (NHet17) and a RARgamma-selective agonist (SHet65) induced similar irritancy as RA. In conclusion, Flex-Hets exhibit improved therapeutic ratios for multiple cancer types over RAR and/or RXR agonists.

Sensitization of cervical cancer cell lines to low-dose radiation by retinoic acid does not require functional p53.

OBJECTIVE: Current therapy for cervical cancer includes radiation therapy. Retinoic acid (RA) can increase the sensitivity of cervical cancer cell lines to radiation. The mechanism of this sensitization may not involve the p53 protein because the human papillomavirus (HPV) E6 protein, which is present in the majority of cervical cancers, promotes p53 degradation. The objective of this study was to determine if p53 is involved in the mechanism of RA radiosensitization. METHOD: The effects of radiation on cervical (SiHa, CC-1, and C33a) and vulvar (SW962) cancer cell lines under various experimental conditions were evaluated using clonogenic, Coulter Counter, electrophoretic mobility shift (EMSA) and a multi-probe RNase protection assay of p53-inducible genes. RESULTS: RA (5 microM 9-cis-RA) radiosensitized the SiHa and CC-1 cell lines that contain HPV-degraded p53, but did not radiosensitize the SW962 cell line, which is HPV negative and contains wild-type p53, nor the C33a cell line, which contains mutant p53 (R273C). Expression of mutant p53 (R273H) in SiHa cells increased the growth rate, but did not prevent RA-induced differentiation or radiosensitization at clinically relevant doses. Inhibition of p53 transactivation with pifithirin alpha did not prevent RA radiosensitization of SiHa at 5 Gy. RA repressed c-fos mRNA expression in control and irradiated SiHa cultures, but did not repress bcl-x(L), p53, GADD45, p21, bax, bcl-2, or mcl-1 mRNA expression. CONCLUSIONS: The mechanism of RA radiosensitization does not require functional p53 and may involve c-fos in cervical cancer cell lines.

A comparison of stages IB1 and IB2 cervical cancers treated with radical hysterectomy. Is size the real difference?

OBJECTIVE: To compare stages IB1 and IB2 cervical cancers treated with radical hysterectomy (RH) and to define predictors of nodal status and recurrence. METHODS: Patients with stage IB cervical cancers undergoing RH between 1990 and 2000 were evaluated and clinicopathological variables were abstracted. The perioperative complication rate, estimated blood loss (EBL), and OR time were also tabulated. Variables were analyzed using X(2) and t tests. Disease-free survival (DFS) was calculated by Kaplan-Meier method. Multivariate analysis was performed via stepwise logistic regression. Cox-proportional hazards were used to identify independent predictors of recurrence. RESULTS: RH was performed on 109 stage IB1 and 86 stage IB2 patients. Mean age, EBL, and perioperative complication rates were similar. Overall, 38 patients (14 IB1 vs. 24 IB2) had positive nodes (P = 0.01) including 9 patients with positive para-aortic nodes (2 IB1 and 7 IB2). Parametrial involvement (PI) and outer 2/3 depth of invasion (DOI) were significantly more common in the IB2 tumors as well. Patients with IB2 disease received adjuvant radiation more frequently than IB1 patients (52% vs. 37%, P = 0.04). Univariate predictors of nodal status included lymphovascular space involvement (LVSI) (P = 0.001), DOI (P = 0.011), PI (P = 0.001), and stage (P = 0.011). Multivariate analysis identified only LVSI (OR 6.4, CI 2.4-17, P = 0. 0002) and PI (OR 8, CI 3.1-20, P = 0. 0001) as independent predictors of positive nodes. With a median follow-up of 35 months, estimates of DFS revealed tumor size (P = 0.008), nodal status (P = 0.0004), LVSI (P = 0.002), PI (P = 0.004), and DOI (P = 0.0004) as significant univariate predictors. Neoadjuvant chemotherapy, age, grade, histology, and adjuvant radiation were not associated with recurrence. The significant independent predictors of DFS were LVSI (ROR 5.7, CI 2-16, P = 0.0064) and outer 2/3 DOI (OR 5.8, CI 2-20, P = 0.0029). Neither tumor size nor nodal status was a significant predictor of DFS. CONCLUSIONS: The prognosis in stage IB cervical cancer seems to be most influenced by presence of LVSI and DOI and not by tumor size as the staging criteria would suggest. These factors are best determined pathologically after radical hysterectomy. This report contains the largest comparison of IB1 and IB2 patients managed by RH. Tumor size failed to predict recurrence or nodal status when stratified by LVSI, DOI, and PI. Treatment decisions based on tumor size alone should be reconsidered.

Surgical-pathological predictors of disease-free survival and risk groupings for IB2 cervical cancer: do the traditional models still apply?

OBJECTIVE: To evaluate how the independent predictors of recurrence for stage IB2 cervical cancers treated with up-front radical hysterectomy apply to established risk models. METHODS: Patients with IB2 cervical cancers diagnosed from 1990 to 2000 were identified from tumor registries of two institutions. Patients were classified into risk groups: high-risk (HR) (positive nodes, parametria, or margins), intermediate-risk (IR) (positive lymph vascular space involvement (LVSI) with any cervical stromal invasion (CSI), or (-) LVSI and > middle- CSI), or low-risk (LR) (absence of HR or IR characteristics). Disease-free survival (DFS) was estimated by Kaplan-Meier method and comparisons between subgroups were studied by log rank. A Cox proportional hazards model was used to determine independent predictors of recurrence. RESULTS: We identified 86 patients with stage IB2 tumors treated by RH. We found 34% of patients to be HR, 60% IR, and 6% LR. Of the 52 IR patients, 28 had (+) LVSI with superficial, middle, and outer 1/3 CSI, and 24 had (-) LVSI with middle or outer 1/3 invasion. Overall, postoperative adjuvant radiation (PRT) was used in 52% of the 86 patients, including 0/5 LR, 16/52 IR, and 29/29 HR patients. Univariate predictors of recurrence were pelvic nodal disease, (+) LVSI, (+) parametria, outer 1/3 CSI, and tumor size > 6 cm. Age, grade, histology, and the use of postoperative radiation were not associated with recurrence. Multivariate analysis identified LVSI as the only independent predictor of recurrence (RR 5.2, P = 0.03). Two-year DFS for LR, IR, and HR patients was 100%, 83%, and 60%, respectively. Only 4/24 (17%) IR patients with (-) LVSI got PRT compared with 12/28 (43%) of IR patients with (+) LVSI. The 2-year DFS for IR patients with (-) LVSI was 96%. IR (+) patients recurred more frequently with a 2-year DFS of 71%. CONCLUSIONS: Overall, 66% of patients with IB2 disease were classified as having low or intermediate-risk disease. IR patients with (-) LVSI and all LR patients did well with surgery alone. This study defines the independent importance of LVSI and questions the utility of published IR models when applied to stage IB2 cervical cancer.