The peritoneal cancer index as a predictor of complete cytoreduction at primary and interval cytoreductive surgery in advanced ovarian cancer.

OBJECTIVE: The peritoneal cancer index quantitatively assesses cancer distribution and tumor burden in the peritoneal cavity. The aim of this study is to evaluate the association between the peritoneal cancer index and completeness of surgical cytoreduction for ovarian cancer and to identify a cut-off above which complete cytoreduction is unlikely. METHODS: This is a single-center prospective cohort observational study. A total of 100 consecutive patients who underwent ovarian cancer surgery were included. Peritoneal cancer index scores prior to and after surgery were calculated, and a cut-off value for incomplete cytoreduction was identified using a receiver operator characteristic (ROC) curve. Surgical complexity, blood loss, length of surgery, and complications were analyzed and associations with the peritoneal cancer index score were evaluated. RESULTS: The overall median peritoneal cancer index score was 9.5 (range 0-36). The median age of the patients was 61 years (range 24-85). The most common stage was III (13% stage II, 53% stage III, 34% stage IV) and the most common histologic sub-type was high-grade serous (76% high-grade serous, 8% low-grade serous, 5% clear cell, 4% serous borderline, 2% endometrioid, 2% adult granulosa cell, 2% adenocarcinoma, 1% carcinosarcoma). Complete cytoreduction was achieved in 82% of patients, with a median score of 9 (range 0-30). The remaining 18% had a median score of 28.5 (range 0-36). The best predictor of incomplete cytoreduction was the peritoneal cancer index score, with an area under the curve (AUC) of 0.928 (95% CI 0.85 to 1.00). ROC curve analysis determined a peritoneal cancer index cut-off score of 20. Major complications occurred in 15% of patients with peritoneal cancer index scores >20 and in 2.5% of patients with scores ≤20, which was statistically significant (p=0.014). CONCLUSIONS: In our study we found that a peritoneal cancer index score of ≤20 was associated with a high likelihood of complete cytoreduction. Incorporating the peritoneal cancer index into routine surgical practice and research may impact treatment plans.

The impact of nutritional risk factors and sarcopenia on survival in patients treated with pelvic exenteration for recurrent gynaecological malignancy: a retrospective cohort study.

PURPOSE: The aim of the present study is to investigate the prognostic significance of nutritional risk factors and sarcopenia on the outcome of patients with recurrent gynaecological malignancies treated by pelvic exenteration. METHODS: We retrospectively evaluated muscle body composite measurements based on pre-operative CT scans, nutritional risk factors as assessed by a validated pre-operative questionnaire, and clinical-pathological parameters in 65 consecutive patients with recurrent gynaecological malignancies, excluding ovarian cancer, treated by pelvic exenteration at the Royal Marsden Hospital London. Predictive value for postoperative morbidity was investigated by logistic regression analyses. Relevant parameters were included in uni- and multivariate survival analyses. RESULTS: We found only (1) low muscle attenuation (MA)-an established factor for muscle depletion-and (2) moderate risk for malnutrition to be independently associated with shorter overall survival (p = 0.006 and p = 0.008, respectively). MA was significantly lower in overweight and obese patients (p = 0.04). Muscle body composite measurements were not predictive for post-operative morbidity. CONCLUSION: The study suggests that pre-operative low MA and moderate risk for malnutrition are associated with shorter survival in patients with recurrent gynaecological malignancies treated with pelvic exenteration. Further studies are needed to validate these findings in larger cohorts.

Chemotherapy Induces Tumor-Associated Macrophages that Aid Adaptive Immune Responses in Ovarian Cancer.

Neoadjuvant chemotherapy (NACT) may stimulate anticancer adaptive immune responses in high-grade serous ovarian cancer (HGSOC), but little is known about effects on innate immunity. Using omental biopsies from HGSOC, and omental tumors from orthotopic mouse HGSOC models that replicate the human tumor microenvironment, we studied the impact of platinum-based NACT on tumor-associated macrophages (TAM). We found that chemotherapy reduces markers associated with alternative macrophage activation while increasing expression of proinflammatory pathways, with evidence of inflammasome activation. Further evidence of a shift in TAM functions came from macrophage depletion via CSF1R inhibitors (CSF1Ri) in the mouse models. Although macrophage depletion in established disease had no impact on tumor weight or survival, CSF1Ri treatment after chemotherapy significantly decreased disease-free and overall survival. This decrease in survival was accompanied by significant inhibition of adaptive immune response pathways in the tumors. We conclude that chemotherapy skews the TAM population in HSGOC toward an antitumor phenotype that may aid adaptive immune responses, and therapies that enhance or sustain this during remission may delay relapse.

Laparoscopic assessment improves case selection for exenterative surgery in recurrent cervical and endometrial cancer.

The objective of this study is to evaluate the role of laparoscopy in the case selection of patients for pelvic exenteration to treat recurrent cervical or endometrial cancer. Pelvic exenteration is a rare surgical procedure performed by specialised multidisciplinary surgical teams. We performed a review of 55 consecutive laparoscopies for patients being evaluated for possible exenterative surgery for recurrent cervical or endometrial cancer at a single centre in the UK with a significant exenterative surgical practice. All patients had no evidence of metastatic disease on imaging prior to the laparoscopy. Despite thorough radiological assessment laparoscopy detected peritoneal, nodal or extrapelvic metastases in 20.8% of cases. 5.6% of the patients who underwent exenterative surgery were found to have unresectable pelvic disease intraoperatively. In these cases, the extent of disease was not determined radiologically or during the initial exploratory laparotomy. In our view, laparoscopic assessment is an essential component of the pre-operative work up of patients with recurrent cervical or endometrial cancer being considered for exenterative surgery.Impact statementWhat is already known on this subject? Pelvic exenteration is potentially curative in cases of recurrent pelvic malignancy. Case selection is essential to determine those patients without metastases and with resectable pelvic disease - this will improve patient outcomes, avoid the unnecessary morbidity of major surgery, as well as the psychological consequences of abandoned procedures. The only two previous studies, published in 1998 (Plante and Roy 1998) and 2002 (Köhler et al. 2002) have shown laparoscopic assessment to be safe and improve case selection.What do the results of this study add? This study provides evidence that in the context of modern imaging modalities, including PET-CT scans, laparoscopic assessment continues to improve case selection for exenterative surgery.What are the implications of these findings for clinical practice and/or further research? This study provides further evidence of the benefit of laparoscopy in the assessment of patients being considered for exenterative surgery for recurrent pelvic cancer. Routine laparoscopy improves case selection and will enhance patient experiences and outcomes.

Clinical management and outcomes of primary ovarian leiomyosarcoma - Experience from a sarcoma specialist unit.

Ovarian sarcomas account for 1% of all ovarian malignancies and amongst these, primary ovarian leiomyosarcoma is the rarest subtype. Primary ovarian leiomyosarcoma has a very poor prognosis, with less than 20% of patients being alive at 5 years. Only a few cases have been published in the literature and there is very limited knowledge on the clinical behaviour and optimal management of these tumours. We have performed a retrospective analysis of a prospectively maintained database to identify all primary ovarian leiomyosarcoma diagnosed and treated at the Royal Marsden NHS Foundation Trust between 1998 and 2020. Sixteen patients were identified from our database and fifteen were eligible for the analysis. Twelve patients presented with localized disease and underwent initial surgery and three patients had metastatic disease at presentation. Recurrence-free survival post-surgery was 16 months. Eight patients received first-line chemotherapy and four patients received second-line chemotherapy. Two patients had indolent metastatic disease and benefited from local therapies only. The median overall survival in the metastatic setting in our cohort was 51 months, which is consistent with previously published cases. Primary ovarian leiomyosarcoma is an extremely rare malignancy with a poor prognosis. This study is the largest case series of primary ovarian leiomyosarcoma published to date, providing clinically important information regarding survival and metastatic rate as well as treatment outcomes in the metastatic setting.

Ovarian Extravascular Papillary Endothelial Hyperplasia (Masson Tumor) Mimicking a Primary Gynecologic Malignancy.

Papillary endothelial hyperplasia or Masson tumor most commonly occurs within the extremities and head and neck. It is usually of intravascular type, associated with thrombus formation and organization within a preexisting vessel or vascular malformation, but rarely can be extravascular. We describe the first 2 cases of this extravascular type to occur within the ovary, one of which mimicked malignancy radiologically. This condition is thought to represent a reactive phenomenon with reparative response secondary to thrombosis although with an unclear underlying pathogenesis. The prognosis is generally good, with complete surgical resection usually representing adequate treatment.

Visualizing the autonomic and somatic innervation of the female pelvis with 3D MR neurography: a feasibility study.

BACKGROUND: Treatment of female pelvic malignancies often causes pelvic nerve damage. Magnetic resonance (MR) neurography mapping the female pelvic innervation could aid in treatment planning. PURPOSE: To depict female autonomic and somatic pelvic innervation using a modified 3D NerveVIEW sequence. MATERIAL AND METHODS: Prospective study in 20 female volunteers (n = 6 normal, n = 14 cervical pathology) who underwent a modified 3D short TI inversion recovery (STIR) turbo spin-echo (TSE) scan with a motion-sensitive driven equilibrium (MSDE) preparation radiofrequency pulse and flow compensation. Modifications included offset independent trapezoid (OIT) pulses for inversion and MSDE refocusing. Maximum intensity projections (MIP) were evaluated by two observers (Observer 1, Observer 2); image quality was scored as 2 = high, 1 = medium, or 0 = low with the sciatic nerve serving as a reference. Conspicuity of autonomic superior (SHP) and bilateral inferior hypogastric plexuses (IHP), hypogastric nerves, and somatic pelvic nerves (sciatic, pudendal) was scored as 2 = well-defined, 1 = poorly defined, or 0 = not seen, and inter-observer agreement was determined. RESULTS: Images were of medium to high quality according to both observers agreeing in 15/20 (75%) of individuals. SHP and bilateral hypogastric nerves were seen in 30/60 (50%) of cases by both observers. Bilateral IHP was seen in 85% (34/40) by Observer 1 and in 75% (30/40) by Observer 2. Sciatic nerves were well identified in all cases, while pudendal nerves were seen bilaterally by Observer 1 in 65% (26/40) and by Observer 2 in 72.5% (29/40). Agreement between observers for scoring nerve conspicuity was in the range of 60%-100%. CONCLUSION: Modified 3D NerveVIEW renders high-quality images of the female autonomic and pudendal nerves.

An Unusual Case of YWHAE-NUTM2A/B Endometrial Stromal Sarcoma With Confinement to the Endometrium and Lack of High-Grade Morphology.

Endometrial stromal sarcoma (ESS) characterized by YWHAE-NUTM2A/B genetic fusion is a recently recognized entity that is classified as a high-grade (HG) ESS in the 2014 World Health Organization Classification. These are myoinvasive neoplasms and typically contain a monomorphous HG round-cell cyclinD1-positive component with or without an accompanying low-grade (LG) component that is only focally positive/negative for cyclinD1. We report a case of YWHAE-NUTM2A/B ESS in a 46-yr-old woman that showed a number of unusual histologic features, including being entirely confined to the endometrium with no myoinvasion or lymphovascular space invasion. The initial hysteroscopic biopsy showed a cyclinD1-positive classic LG ESS-like component which merged with a smaller cyclinD1 negative/focally positive fibroblastic component with no HG areas. YWHAE-NUTM2A/B genetic fusion was shown by real-time quantitative polymerase chain reaction and Sanger sequencing. In the subsequent hysterectomy specimen, the tumor was entirely confined to the endometrium and was largely composed of cellular and classic LG ESS-like areas (80%) which were strongly and diffusely positive for cyclinD1 and a focal fibroblastic component (20%) which was largely cyclinD1 negative. Despite the cellular areas showing mild nuclear enlargement, the entire tumor had a very low mitotic and proliferation index and showed strong and diffuse positivity for estrogen and progesterone receptors. The patient remains alive and well with no evidence of disease 14 mo following diagnosis. To our knowledge, this is the first reported case of YWHAE-NUTM2A/B ESS that is confined to the endometrium and which exhibits entirely LG morphology.

Selective marginal resections in the management of aggressive angiomyxomas.

AIM: Aggressive angiomyxomas (AA) are rare tumors, most commonly presenting in the pelvis of women of childbearing age. This study presents the results of selective marginal resection of this disease in patients managed at a single institution. METHODS: Patients diagnosed with AA from July 2001 to July 2015 were identified from a prospectively maintained histopathology database. RESULTS: Seventeen patients were diagnosed with AA in the study period. The median age at diagnosis was 48 years. Females were more commonly affected with a M:F of 1:8.5. The most common differential diagnoses were an ischiorectal abscess or Bartholin's cyst. Fifteen cases occurred in the pelvis, with two cases at other sites. Median maximum tumor diameter was 10 cm. Of the pelvic cases, 12 were managed operatively via perineal, abdominal, or abdominoperineal approaches. Excision was performed in a marginal fashion with minimal morbidity. Local recurrence developed in 58.3% with a median local recurrence free survival of 25 months. No patients developed metastatic disease or died from disease. CONCLUSION: AA are rare tumors with a propensity for local recurrence. Atypical presentations of other perineal pathologies should prompt further investigation. Surgery should be reserved for symptomatic patients and is associated with low rates of morbidity. J. Surg. Oncol. 2016;114:828-832. © 2016 2016 Wiley Periodicals, Inc.

Outcome of Appendicectomies at Surgery for Mucinous Ovarian Neoplasms: Report From A UK Center and Review of Literature.

OBJECTIVE: This study aimed to determine the frequency of malignant pathology in a macroscopically normal appendix during surgery for a borderline or malignant mucinous ovarian tumor (MOT). METHODS: Women with borderline and malignant MOT were identified from the pathology database from 2000 to 2014. Women who had a benign MOT and had an appendicectomy were excluded from the study. Data were collected from the electronic patient record and case notes. RESULTS: Of 310 women identified with MOT, 203 patients with benign MOT were excluded. Of the remaining 107 patients, 15 patients with previous appendicectomy were also excluded. The study population consisted of 92 patients. There were 57 (62%) patients with borderline MOT and 35 (38%) patients with malignant MOT. In the borderline subgroup, 40/57 (70%) patients had appendicectomy of whom 8 (20%) had macroscopically abnormal appendices. One patient had pseudomyxoma peritonei secondarily involving the appendix and 7 patients had a histologically normal appendix. Normal histology was found in all macroscopically normal appendices. In the malignant subgroup, 29/35 (83%) patients had an appendicectomy. There were 8 (27.5%) macroscopically abnormal appendices with a malignant pathology in 7 (87.5%) patients and 1 patient had a resolving appendicitis. There were 21 macroscopically normal appendices of which, serrated adenoma was found in 1 (4.8%) patient, whereas the remaining 20 (95.2%) patients had normal histology. CONCLUSIONS: In MOT, an abnormal appearing appendix should be excised. If the appendix is grossly normal, our data do not support performing an appendicectomy as part of a surgical staging procedure.

Human Peritoneal Mesothelial Cells Display Phagocytic and Antigen-Presenting Functions to Contribute to Intraperitoneal Immunity.

Mesothelial cells lining the peritoneal cavity are strategically positioned to respond to and counter intraperitoneal infections, cancer cells, and other challenges. We have investigated human peritoneal mesothelial cells (HPMCs) for phagocytic activity, expression of surface Major Histocompatibility Complex (MHC) class II and accessory molecules involved in antigen presentation, and the ability to present recall antigens to T cells. Phagocytosis of dextran, latex beads, and Escherichia coli was observed by flow cytometry, and internalization was visualized using confocal and electron microscopy. Flow cytometry and/or cellular enzyme-linked immunosorbent assay showed constitutive expression of ICAM-1, LFA-3, and B7-1, but not B7-2 or MHC class II. Interferon-gamma induced MHC II and ICAM-1 expression in a dose- and time-dependent manner. Importantly, HPMCs induced autologous CD3 T-lymphocyte proliferation (H incorporation) after pulse with recall antigen. Human peritoneal mesothelial cells equipped with phagocytic and antigen-presenting machinery are anticipated to have an integral role in intraperitoneal immune surveillance.

Venous thromboembolism at time of diagnosis of ovarian cancer: Survival differs in symptomatic and asymptomatic cases.

OBJECTIVES: To determine the impact on survival of symptomatic and asymptomatic venous thromboembolism (VTE) at time of diagnosis of primary ovarian malignancy. MATERIALS AND METHODS: The clinical records of 397 consecutive cases of primary ovarian malignancy were studied. Clinical, pathological and survival data were obtained. RESULTS AND CONCLUSIONS: Of 397 cases, 19 (4.8%) were found to have VTE at diagnosis, of which 63.2% (n=12) were asymptomatic. VTE was significantly associated with reduced overall median survival (28 vs. 45 months, p=0.004). Decreased survival was associated with symptomatic VTE compared to patients with asymptomatic VTE (21 vs. 36 months, p=0.02) whose survival was similar to that of patients without VTE. Decreased survival remained significant in symptomatic patients after controlling for stage of disease at diagnosis, cytoreductive status and adjuvant chemotherapy use. Overall these data suggest for the first time that symptomatic but not asymptomatic VTE prior to primary treatment of ovarian cancer is an independent adverse prognostic factor.

Exenterative surgery for recurrent gynaecological malignancies.

BACKGROUND: Cancer is a leading cause of death worldwide. Gynaecological cancers (i.e. cancers affecting the ovaries, uterus, cervix, vulva and vagina) are among the most common cancers in women. Unfortunately, given the nature of the disease, cancer can recur or progress in some patients. Although the management of early-stage cancers is relatively straightforward, with lower associated morbidity and mortality, the surgical management of advanced and recurrent cancers (including persistent or progressive cancers) is significantly more complicated, often requiring very extensive procedures. Pelvic exenterative surgery involves removal of some or all of the pelvic organs. Exenterative surgery for persistent or recurrent cancer after initial treatment is difficult and is usually associated with significant perioperative morbidity and mortality. However, it provides women with a chance of cure that otherwise may not be possible. In carefully selected patients, it may also have a place in palliation of symptoms. The biology of recurrent ovarian cancer differs from that of other gynaecological cancers; it is often responsive to chemotherapy and is not included in this review. OBJECTIVES: To evaluate the effectiveness and safety of exenterative surgery versus other treatment modalities for women with recurrent gynaecological cancer, excluding recurrent ovarian cancer (this is covered in a separate review). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to February 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of clinical guidelines and review articles and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) or non-randomised studies with concurrent comparison groups that included multivariate analyses of exenterative surgery versus medical management in women with recurrent gynaecological malignancies. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. No studies were found; therefore no data were analysed. MAIN RESULTS: The search strategy identified 1311 unique references, of which seven were retrieved in full, as they appeared to be potentially relevant on the basis of title and abstract. However, all were excluded, as they did not meet the inclusion criteria of the review. AUTHORS' CONCLUSIONS: We found no evidence to inform decisions about exenterative surgery for women with recurrent cervical, endometrial, vaginal or vulvar malignancies. Ideally, a large RCT or, at the very least, well-designed non-randomised studies that use multivariate analysis to adjust for baseline imbalances are needed to compare exenterative surgery versus medical management, including palliative care.

The use of laparostomy in patients with gynecologic cancer: first report from a UK cancer center.

OBJECTIVE: To report on the use of laparostomy after major gynecologic cancer surgery. METHODS: Operative records and surgical databases of patients who underwent major open abdominal surgery over a 6.5-year period at a tertiary referral center were searched. Patients who had diagnostic procedures, operative laparoscopy, and surgery for vulval cancer were excluded. All patients who had laparostomy were identified; and the diagnosis, indication for laparostomy, method of temporary cover, and complications were recorded. RESULTS: A total of 1592 laparotomies, including 37 emergencies, were performed. Of these, 14 patients (0.88%) had a laparostomy. Seven patients had primary cancer and 7 had recurrent cancer. As more patients had surgery for primary disease, laparostomy was more common in patients who underwent surgery for recurrent cancer. Seven patients had ovarian/fallopian tube/primary peritoneal cancer, 4 patients had uterine cancer, 2 patients had cervical cancer, and one patient had vaginal cancer. Ten laparostomies (71.4%) were performed after an emergency procedure; thus, laparostomy was approximately 100 times more common after emergency than elective major surgery. Massive bowel distension and bowel wall edema were the major indications for laparostomy. The method of temporary closure was variable, and a sterile saline bag was the most commonly used. The laparostomy was closed in all but 2 patients, most often on postoperative day 2 or 3. Two patients (14.3%) died within 30 days of the laparostomy, and 2 others died at postoperative days 40 and 62. Three of these 4 patients had recurrent cancer, and 2 patients had emergency procedures. CONCLUSIONS: The overall incidence of laparostomy associated with laparotomy for gynecological cancer surgery was less than 1:100 cases, was more common after surgery for recurrent cancer, and in particular, was approximately 100 times more common after emergency procedures. The 30-day operative mortality rate was 14.3%.

Relationship between imaging biomarkers of stage I cervical cancer and poor-prognosis histologic features: quantitative histogram analysis of diffusion-weighted MR images.

OBJECTIVE: The purpose of this study was to determine whether histogram analysis of apparent diffusion coefficient (ADC) values from diffusion-weighted MRI can be used to differentiate cervical tumors according to their histologic characteristics. SUBJECTS AND METHODS: Sixty patients with International Federation of Gynecology stage I cervical cancer underwent MRI at 1.5 T with a 37-mm-diameter endovaginal coil. T2-weighted images (TR/TE, 2000-2368/90) followed by diffusion-weighted images (TR/TE, 2500/69; b values, 0, 100, 300, 500, and 800 s/mm(2)) were acquired. An expert observer drew regions of interest around a histologically confirmed tumor on ADC maps by referring to the T2-weighted images. Pixel-by-pixel ADCs were calculated with a monoexponential fit of data from b values of 100-800 s/mm(2), and ADC histograms were obtained from the entire tumor volume. An independent samples Student t test was used to compare differences in ADC percentile values, skew, and kurtosis between squamous cell carcinoma and adenocarcinoma, well or moderately differentiated and poorly differentiated tumors, and absence and presence of lymphovascular space invasion. RESULTS: There was no statistically significant difference in ADC percentiles between squamous cell carcinoma and adenocarcinoma, but the median was significantly higher in well or moderately differentiated tumors (50th percentile, 1113 ± 177 × 10(-6) mm(2)/s) compared with poorly differentiated tumors (50th percentile, 996 ± 184 × 10(-6) mm(2)/s) (p = 0.049). Histogram skew was significantly less positive for adenocarcinoma compared with squamous cell carcinoma (p = 0.016) but did not differ between tumor grades. There was no significant difference between any parameter with regard to lymphovascular space invasion. CONCLUSION: Median ADC is lower in poorly compared with well or moderately differentiated tumors, while lower histogram-positive skew in adenocarcinoma compared with squamous cell carcinoma is likely to reflect the glandular content of adenocarcinoma.

Surgical management of bowel obstruction in gynaecological malignancies.

PURPOSE OF REVIEW: Bowel obstruction in gynaecological malignancies continues to present clinical challenges and a multidisciplinary approach to discuss management is crucial. Surgery, usually with palliative intent, is associated with significant morbidity and mortality. There is an absence of level 1 evidence and national guidelines, and only limited quality-of-life data. RECENT FINDINGS: Acute bowel obstruction in gynaecological cancer patients is rare and surgery is associated with a higher morbidity and mortality rate. Less commonly, emergency bowel obstruction cases will have had radiotherapy or recent chemotherapy, which also increases surgical morbidity and mortality. However, most often, bowel obstruction in irradiated gynaecological cancer patients is not due to cancer. Ovarian cancer is the most common malignancy. Caution is needed in those EOC patients with ascites, short treatment-free interval, acute abdomen and chemoresistance. Comorbidities are frequent. The decision for surgery should be made on an individual basis. Palliative care input is important early in patient management as for most patients the surgical goal is palliation and not cure. There is still a paucity of published data on quality-of-life assessments. SUMMARY: There is a need to identify those patients who may benefit from palliative surgical intervention and those who will not. Ideally, agreed national guidelines should be produced and regularly reviewed.

Doubling time of serum CA125 is an independent prognostic factor for survival in patients with ovarian cancer relapsing after first-line chemotherapy.

INTRODUCTION: Confirmed doubling of CA125 value is one definition of progression in ovarian cancer patients. If asymptomatic, the management of these patients is unclear. To provide information which may assist in therapeutic decision making, we set out to determine the independent prognostic significance for the rate of rise in CA125 during surveillance in ovarian cancer patients as measured by CA125 doubling time. PATIENT AND METHODS: Clinical information was obtained through a 2-staged chart review of ovarian cancer patients treated in our department from 1994 to 2003. We searched for patients who met criteria for CA125 progression and doubling during surveillance following first-line therapy. RESULTS: A total of 296 patients were initially identified. During surveillance, the median doubling time of CA125 was 40 d and the median survival for patients with a CA125 doubling time of 40 d was 10.6 months compared to 22.1 months for those with doubling time>40 d. In a univariate analysis, age, high-grade, suboptimal cytoreduction, short CA125 doubling time, short time to progression and high CA125 at progression were significantly associated with poor survival, but in a multivariate analysis, a short CA125 doubling time of