Capillary Lymphatic Space Involvement Research Articles

Metastasis to deep obturator and para-aortic lymph nodes in 649 patients with cervical carcinoma

Objective The extent of retroperitoneal lymph node dissection for early stage cervical cancer remains debatable. Our study aimed to investigate the incidence of metastases in deep obturator lymph nodes (DOLNs) and para-aortic lymph nodes (PALNs) and its association with clinicopathological factors in cervical carcinoma. Method Six hundred and forty-nine patients with stage IB to IIB cervical cancer underwent radical hysterectomy, pelvic lymphadenectomy and/or para-aortic lymphadenectomy. The incidence and distribution of metastases in retroperitoneal lymph nodes and the associated factors were analyzed. Results Metastases in pelvic lymph nodes (PLNs) were found in 175 patients. Of the 175 cases with positive PLNs, 15 had DOLN metastases. Only two cases without PLN metastases had positive DOLNs. There was no significant correlation between DOLN metastasis and tumor histology, differentiation or capillary lymphatic space involvement. PALN metastasis occurred in 19 of 137 patients with cervical lesions larger than 2 cm in diameter. Eighteen of the 19 patients also had PLN involvement. Logistic regression analysis showed that PLN metastasis and larger tumors were independent risk factors for metastasis to PALNs. Conclusion DOLN metastasis is not common and may be secondary to metastasis to other PLNs. Routine removal of DOLNs might be unnecessary when PLNs are negative. Para-aortic sampling or lymphadenectomy should be considered when the PLNs are positive or/and the cervical lesion is larger than 2 cm.

The Usefulness of Photodynamic Eye for Sentinel Lymph Node Identification in Patients with Cervical Cancer

We studied the potential use of sentinel lymph node identification using a near-infrared fluorescence imaging technique in the treatment of cervical cancer. Directly before the start of the operation, 0.2 ml of 5 mg/ml indocyanine green was prepared and injected into 4 sites in the cervix using a 26-gauge standard needle, at 3, 6, 9 and 12 o'clock positions. When the operation was advanced to the pelvis, near-infrared fluorescence imaging was performed using photodynamic eye (Hamamatsu Photonics Co., Japan). The sentinel lymph nodes and other dissected lymph nodes were histologically examined to find any metastases. Twelve patients were examined. Their ages ranged from 36 to 68 years (median, 58). Sentinel lymph nodes were identified in 10 patients (83%), and all were bilaterally identified. The median maximum tumor diameter of dissected cervical tumors was 35 mm (22-65); histology was squamous cell carcinoma in 8 patients and adenocarcinoma in 2 patients. Capillary lymphatic space involvement was found in 8 of the 10 patients. The site of the sentinel lymph node was the right external iliac node in 8 patients, the right obturator node in 8, the left external iliac node in 9, and the left obturator node in 8. Lymph node metastasis was found in 2 of the 12 patients, and all were sentinel lymph nodes. No metastasis from lymph nodes other than sentinel lymph nodes was observed. Photodynamic eye achieved a detection rate similar to that obtained with the blue dye and radioisotope method. It is also easier to use than the other two methods.

Evaluation of Two Management Strategies for Preoperative Grade I Endometrial Cancer

OBJECTIVE To compare the practices, adjuvant treatment, and outcomes of patients with preoperatively assessed grade 1 endometrioid endometrial cancer between two academic gynecologic oncology centers that use different treatment strategies. METHODS A retrospective analysis was performed at Duke University Medical Center (Duke) and the Toronto Sunnybrook Regional Cancer Center (Sunnybrook) between 1991 and 2007. Patients at Duke generally underwent surgical staging unless intraoperative assessment identified a negligible risk of nodal disease. Patients at Sunnybrook generally did not undergo surgical staging. RESULTS A total of 494 patients (272 from Duke and 222 from Sunnybrook were identified with preoperative, central-review-confirming, grade 1, endometrioid, endometrial cancer. Groups were similar in grade, final histology, type of hysterectomy, and length of hospital stay. Patients from Sunnybrook were older (aged 62 years compared with 59 years, P=.001) and were more likely to have capillary lymphatic space involvement (18.2% compared with 8.3%, P=.003) and cervical involvement (12.2% compared with 3.7%, P<.001). Approximately 2% of cases were upgraded to high grade on final specimen. Lymphadenectomy was performed on 49.4% of patients at Duke compared with 11.7% of patients at Sunnybrook. Overall 3-year survival was 96% at Duke and 96% at Sunnybrook (P=.217). Three-year recurrence-free survival was 96% at Duke and 95% at Sunnybrook (P=.327). CONCLUSION Despite differences in practice and slight differences in patient populations, the recurrence-free and overall survival of women with preoperative centrally reviewed grade 1 endometrial cancer is excellent and without statistically significant difference between the two centers. LEVEL OF EVIDENCE III

Postoperative concurrent nedaplatin-based chemoradiotherapy improves survival in early-stage cervical cancer patients with adverse risk factors

Objectives The aim of this study was to evaluate the efficacy of postoperative nedaplatin-based concurrent chemoradiotherapy (CCRT) in patients with FIGO stage IA2–IIB cervical cancer with adverse risk factors. Methods We retrospectively reviewed the medical records of 183 patients with early-stage cervical cancer who had undergone radical surgery between April 1997 and March 2006. Of these, 68 patients displayed high-risk prognostic factors such as positive pelvic lymph nodes, parametrial involvement, or a positive surgical margin. Fifty-seven patients demonstrated intermediate-risk prognostic factors including deep stromal invasion, capillary lymphatic space involvement, or large tumor diameter. These patients were treated postoperatively with CCRT or radiotherapy alone (RT). Fifty-eight patients showed no risk factors and, therefore, received no adjuvant therapy after surgery. The 3-year recurrence rate, progression free survival (PFS), and overall survival (OS) were compared between the treatment groups. Results CCRT was significantly superior to RT alone with regard to recurrence rate, PFS, and OS in patients that displayed high-risk and intermediate-risk prognostic factors. The frequencies of acute grade 3–4 toxicities were significantly higher in patients treated with CCRT than in those treated with RT alone. However, no statistically significant difference was observed with regard to severe late toxicities. Conclusions Postoperative nedaplatin-based CCRT was safely performed and improved the prognosis of FIGO stage IA2–IIB cervical cancer patients displaying high-risk or intermediate-risk prognostic factors. This treatment can be considered as an alternative to cisplatin-based chemoradiotherapy in this patient population.

Evaluation of Two Management Strategies for Preoperative Grade 1 Endometrial Cancer

To compare the practices, adjuvant treatment, and outcomes of patients with preoperatively assessed grade 1 endometrioid endometrial cancer between two academic gynecologic oncology centers that use different treatment strategies. A retrospective analysis was performed at Duke University Medical Center (Duke) and the Toronto Sunnybrook Regional Cancer Center (Sunnybrook) between 1991 and 2007. Patients at Duke generally underwent surgical staging unless intraoperative assessment identified a negligible risk of nodal disease. Patients at Sunnybrook generally did not undergo surgical staging. A total of 494 patients (272 from Duke and 222 from Sunnybrook were identified with preoperative, central-review-confirming, grade 1, endometrioid, endometrial cancer. Groups were similar in grade, final histology, type of hysterectomy, and length of hospital stay. Patients from Sunnybrook were older (aged 62 years compared with 59 years, P=.001) and were more likely to have capillary lymphatic space involvement (18.2% compared with 8.3%, P=.003) and cervical involvement (12.2% compared with 3.7%, P<.001). Approximately 2% of cases were upgraded to high grade on final specimen. Lymphadenectomy was performed on 49.4% of patients at Duke compared with 11.7% of patients at Sunnybrook. Overall 3-year survival was 96% at Duke and 96% at Sunnybrook (P=.217). Three-year recurrence-free survival was 96% at Duke and 95% at Sunnybrook (P=.327). Despite differences in practice and slight differences in patient populations, the recurrence-free and overall survival of women with preoperative centrally reviewed grade 1 endometrial cancer is excellent and without statistically significant difference between the two centers. III

Postoperative radiation therapy improves prognosis in patients with adverse risk factors in localized, early-stage cervical cancer: a retrospective comparative study

The objective of this study was to assess the role of postoperative radiotherapy (RT) in early-stage cervical carcinoma with risk factors other than positive nodes, parametrial invasion, or positive margins and to compare outcomes using the Leiden University Medical Center (LUMC) modification of the Gynecologic Oncology Group (GOG) system with the GOG prognostic scoring system itself. Between January 1984 and April 2005, 402 patients with early-stage cervical cancer underwent radical hysterectomy. A total of 51 patients (13%) had two of the three risk factors and had pathologic tumor size (> or =40 mm), invasion (> or =15 mm), and capillary lymphatic space involvement, and were identified as the so-called high-risk (HR). We compared 34 patients who received RT based on the LUMC risk profile (67%) with 17 who did not (33%). The GOG score was calculated as well. We compared the GOG scores within the LUMC risk groups: HR+ (two out of three risk factors) and HR- (less than two out of three risk factors). Differences in 5-year cancer-specific survival (CSS) and 5-year disease-free survival (DFS) between the HR group treated with RT (86%, 85%) and without RT (57%; 43%) were statistically significant. The LUMC criteria did not significantly differ from the GOG risk profile, concerning recurrence, CSS, and DFS. HR patients benefit from adjuvant RT. The LUMC modification of the GOG system seems to be simpler and has a slightly higher threshold for the indication for RT but without a difference in outcome.

A phase III randomized trial of postoperative pelvic irradiation in stage IB cervical carcinoma with poor prognostic features: Follow-up of a gynecologic oncology group study

To investigate, in a phase III randomized trial, whether postoperative external-beam irradiation to the standard pelvic field improves the recurrence-free interval and overall survival (OS) in women with Stage IB cervical cancers with negative lymph nodes and certain poor prognostic features treated by radical hysterectomy and pelvic lymphadenectomy. Eligible patients had Stage IB cervical cancer with negative lymph nodes but with 2 or more of the following features: more than one third (deep) stromal invasion, capillary lymphatic space involvement, and tumor diameter of 4 cm or more. The study group included 277 patients: 137 randomized to pelvic irradiation (RT) and 140 randomized to observation (OBS). The planned pelvic dose was from 46 Gy in 23 fractions to 50.4 Gy in 28 fractions. Of the 67 recurrences, 24 were in the RT arm and 43 were in the OBS arm. The RT arm showed a statistically significant (46%) reduction in risk of recurrence (hazard ratio [HR] = 0.54, 90% confidence interval [CI] = 0.35 to 0.81, p = 0.007) and a statistically significant reduction in risk of progression or death (HR = 0.58, 90% CI = 0.40 to 0.85, p = 0.009). With RT, 8.8% of patients (3 of 34) with adenosquamous or adenocarcinoma tumors recurred vs. 44.0% (11 of 25) in OBS. Fewer recurrences were seen with RT in patients with adenocarcinoma or adenosquamous histologies relative to others (HR for RT by histology interaction = 0.23, 90% CI = 0.07 to 0.74, p = 0.019). After an extensive follow-up period, 67 deaths have occurred: 27 RT patients and 40 OBS patients. The improvement in overall survival (HR = 0.70, 90% CI = 0.45 to 1.05, p = 0.074) with RT did not reach statistical significance. Pelvic radiotherapy after radical surgery significantly reduces the risk of recurrence and prolongs progression-free survival in women with Stage IB cervical cancer. RT appears to be particularly beneficial for patients with adenocarcinoma or adenosquamous histologies. Circumstances that may have influenced the overall survival differences are considered.

Postoperative radiation therapy improves prognosis in patients with adverse risk factors in localized, early-stage cervical cancer: a retrospective comparative study

The objective of this study was to assess the role of postoperative radiotherapy (RT) in early-stage cervical carcinoma with risk factors other than positive nodes, parametrial invasion, or positive margins and to compare outcomes using the Leiden University Medical Center (LUMC) modification of the Gynecologic Oncology Group (GOG) system with the GOG prognostic scoring system itself. Between January 1984 and April 2005, 402 patients with early-stage cervical cancer underwent radical hysterectomy. A total of 51 patients (13%) had two of the three risk factors and had pathologic tumor size (≥40 mm), invasion (≥15 mm), and capillary lymphatic space involvement, and were identified as the so-called high-risk (HR). We compared 34 patients who received RT based on the LUMC risk profile (67%) with 17 who did not (33%). The GOG score was calculated as well. We compared the GOG scores within the LUMC risk groups: HR+ (two out of three risk factors) and HR− (less than two out of three risk factors). Differences in 5-year cancer-specific survival (CSS) and 5-year disease-free survival (DFS) between the HR group treated with RT (86%, 85%) and without RT (57%; 43%) were statistically significant. The LUMC criteria did not significantly differ from the GOG risk profile, concerning recurrence, CSS, and DFS. HR patients benefit from adjuvant RT. The LUMC modification of the GOG system seems to be simpler and has a slightly higher threshold for the indication for RT but without a difference in outcome.

TRATAMIENTO ADYUVANTE DEL CÁNCER CÉRVICO UTERINO: FACTORES DE RIESGO, INDICACIONES Y TRATAMIENTO

SUMMARY The identification of various pathologic risk factors and a better stratification of patients into risk groups, after primary surgical management of early stage cervical cancer, helps to define the best adjuvant treatment and improve outcomes. Two randomized clinical trials have greatly advanced our understanding of the role of adjuvant treatment in cervix cancer. In patients with clinical stage IA2, IB and IIA carcinoma of the cervix initially treated with radical hysterectomy and pelvic lymphadenectomy and who have positive pelvic lymph nodes, and/or positive surgical margins, and/or microscopic involvement of the parametrium the use of combined adjuvant radiation and chemotherapy significantly improves overall survival and progession-free survival compared with pelvic radiation therapy alone. For women with stage IB cervical cancer treated by radical hysterectomy and pelvic lymphadenectomy, with node-negative and at least two of the following risk factors: >1/3 stromal invasion, capillary lymphatic space involvement and large clinical tumor diameter adjuvant pelvic radiation therapy significantly improves relapse-free survival compared with no further therapy. Further improvement in outcomes for high risk, early stage cervical cancer patients will come from enhanced definition of prognostic factors and risk groups, better patient selection for primary treatment and better local and systemic therapies.

Blood transfusion and the risk of recurrence in squamous cell carcinoma of the cervix: a gynecologic oncology group study.

The objective of this study was to determine whether perioperative blood transfusion adversely affected risk of recurrence in 504 evaluable patients with stage I squamous cell carcinoma of the cervix accessioned prospectively in a Gynecologic Oncology Group study. After eliminating patients with advanced-stage disease, wrong cell type, and those without transfusion information available, 504 of 1,125 patients accrued to Gynecologic Oncology Group Protocol 49 were included in this study. Seventy-seven percent of the patients received blood products within 2 weeks of surgery. Either the Pearson chi-square or Fisher exact test assesses the association of categorical clinical-pathologic factors with respect to transfusion status. Cox's proportional hazards model was used to identify and simultaneously evaluate the independent prognostic factors associated with survival and recurrence-free interval (RFI). The number of units transfused was found to be significantly related to RFI and survival using univariate analysis. When adjusted for clinical tumor size, capillary-lymphatic space involvement, and depth of tumor invasion using multivariate analysis, the number of units transfused was no longer statistically significant with respect to either RFI or survival. Recurrence and survival in patients with squamous cell cancer of the cervix could not be shown to be independently related to transfusion status.

Significant decreased complications, based on individualized post-radical hysterectomy irradiation for carcinoma cervix - FIGO stage IB with unfavorable prognostic factors

Purpose: To evaluate long term cancer control and treatment complications of vaginal intracavitary brachytherapy in conjunction with reduced external beam RT tailored to individual unfavorable pathologic findings in patients with FIGO Stage IB cancer cervix. Materials and Methods: Between 1980 and 1995, 64 patients post-radical hysterectomy with positive pelvic nodal metastases or any of the following risk factors: > 1cm. stromal invasion, capillary lymphatic space involvement, and large clinical tumor diameter(>3 cm.) received postoperative adjuvant radiation therapy. The histological findings include: 46 squamous carcinoma, 16 adenocarcinoma, 1 adenosquamous and 1glassy cell carcinoma. 16 patients had pelvic nodal metastases. None of the patients received adjuvant chemotherapy. Fourteen patients were treated on GOG-92 protocol that delivers 5000 cGy external beam radiation, post radical hysterectomy for women with poor prognostic factors. The remaining 50 patients were treated with individualized adjuvant radiotherapy and are the basis for this paper. External beam radiotherapy consisted of whole pelvic treatment of 45Gy/25 fractions /5 weeks using a 4-field technique. Pelvic node positive patients received an additional 5.4 Gy pelvic boost using a 4 cm. midline block. Both groups, node positive and negative then received 25 Gy vaginal intacavitary LDR brachytherapy(mucosal dose); to increase the dose to the vaginal apex, an area considered to be at high-risk for local recurrence. Median follow-up was 82 months; all survivors were followed for a minimum 3 years - with periods ranging from 36 to 220 months. Two patients were lost to follow-up before completing the 3-year period. Results: The actuarial recurrence-free survival (local or distant) for the vaginal boost group (node negative and positive) was 88 % at 5 years. Of the 8 patients who failed; there was 1 vaginal cuff recurrence(2%), two pelvic recurrences(4%) and 5 with distant metastases (10%) . A subgroup of 27 patients that conformed to the risk criteria combination used in the GOG-92 study was analysed. The actuarial recurrence - free survival for this group was 87.5 % at 5 years, slightly better than 82.5% for the GOG study. There was an 11.1% rate of locoregional recurrences. (2 pelvic and 1 vaginal cuff), which corresponded to the GOG failure rate of 13.1%. Grade 3 and 4 side effects were non-existent. In contrast GOG-92 reported a 9 % incidence of grade 3-4 effects with one Grade 5 mortality. The 16 node positive patients showed a 75% 5 year Recurrence - free survival with a 0% local recurrence. Conclusion: The individualized use of adjuvant radiation therapy based on unfavorable pathological features used in this series was very effective in achieving loco-regional control, without Grade 3 and 4 complications. The application of adjuvant vaginal brachytherapy to increase vaginal apex dose, enabled a reduction in external beam pelvic dose .These results show the advantages for post-radical hysterectomy irradiation in patients with Stage IB carcinoma of the uterine cervix with poor prognostic features. The high incidence of grade 3 and 4 complications in GOG-92 questioned the use of adjuvant irradiation despite statistical benefits of control of disease. This paper shows such an argument is without merit with a small change in technique.

Changes in the Demographics and Perioperative Care of Stage IA2/IB1 Cervical Cancer over the Past 16 Years

Objectives. The aim of this study was to determine whether there have been any significant changes in the demographics and perioperative care of FIGO stage IA2/IB1 cervical cancer over the past 16 years and, if so, to quantify them.Methods. Since July 1984, all patients with FIGO stage IA2/IB1 cervical cancer undergoing radical surgery by members of our division have been entered into a prospective database. Selection for surgery has been unchanged over the past 16 years. Since March 1994 and November 1996, one surgeon has performed radical vaginal trachelectomy and laparoscopic assisted radical vaginal hysterectomy, respectively. Statistical analysis used Spearman's correlation analysis, the proportional hazards regression model of Cox, and the Mantel–Hanzel test was performed. Due to the number of statistical analyses, statistical significance was defined as P < 0.01.Results. Eight hundred sixty-four patients have undergone radical surgery (784 radical hysterectomy, 42 radical vaginal trachelectomy, 32 radical vaginal hysterectomy, 6 radical abdominal trachelectomy) for FIGO stage IA2/IB1 carcinoma of the cervix by members of our division since 1984. There have been no changes in the median age (40 years), tumor size (2.0 cm), incidence of capillary lymphatic space involvement (47%), or positive pelvic lymph nodes (6%) over the past 16 years. The median Quetelet index (24.6), depth of tumor invasion (squamous cell carcinomas only) (6.0 mm), and proportion of patients with comorbid conditions (17%) have increased over time (P = 0.001, P = 0.003, and P < 0.001, respectively). Pathologically, there has been an increase in the proportion of adenocarcinomas (28%) and a decrease in the proportion of grade 3 tumors (28%) (P < 0.001 and P < 0.001, respectively). The median operating time (2.8 h), hospital stay (7.0 days), blood loss (600 cc), allogeneic blood transfusion (23%), postoperative infections (13%), and noninfectious complications (6%) have all decreased (P < 0.001, P < 0.001, P < 0.001, P < 0.001, P < 0.001, and P = 0.002, respectively). There has been no change in the incidence of positive surgical margins (3%), adjuvant radiation (13%), or recurrence-free survival (2 and 5 years, 94 and 90%, respectively) after a median follow-up of 45 months.Conclusion. Despite no substantive changes in the selection criteria for surgery and the small time interval studied (16 years), almost all indices of operative and postoperative morbidity analyzed have decreased significantly. These changes have occurred without an increase in the use of adjuvant radiation or decrease in recurrence-free survival. Although little progress has been made in the cure rates associated with surgical management of FIGO stage IA2/IB1 cervical cancer during this time interval, it appears that the morbidity of surgery has decreased.

Is radical trachelectomy a safe alternative to radical hysterectomy for patients with stage IA-B carcinoma of the cervix?

The prognosis associated with lymph node negative, early stage carcinoma of the cervix is excellent, with 5-year survival rates greater than 90%. Radical trachelectomy in combination with pelvic lymph node dissection (RVT + LPL) has emerged as an alternative to radical hysterectomy (RH) for these patients who desire preservation of fertility. However, there are limited data to support its efficacy and safety. All patient information was collected prospectively and was subsequently extracted from the cervical cancer surgery database of the Division of Gynecologic Oncology at the University of Toronto. Patients treated by RVT + LPL for fertility preservation were compared with two groups of patients treated by RH. One control group was matched for age, tumor size, histology, depth of invasion, presence of capillary lymphatic space involvement, lymph node metastases, and use of adjuvant radiation. The other control group consisted of patients with tumor sizes </=2 cm, negative pelvic lymph nodes who had not received adjuvant radiation therapy. Thirty of 32 patients treated by RVT + LPL between March 1994 and November 1998 were matched. The only statistically significant difference in prognostic factors between the patients who underwent RVT + LPL and unmatched controls (556 patients) was the median depth of invasion in the adenocarcinomas (2. 0 mm vs. 4.0 mm, respectively; P < 0.02). The 2-year actuarial recurrence free survival was 95%, 100%, and 97% for the patients who underwent RVT + LPL, matched controls, and unmatched controls, respectively. The actuarial conception rate at 12 months was 37%. Acknowledging the small numbers and short follow-up, RVT + LPL appears to be similar in efficacy to RH. If longer follow-up with more patients confirms the above, this procedure will represent an acceptable alternative to RH for patients with early Stage I carcinoma of the cervix who desire preservation of fertility.

A Randomized Trial of Pelvic Radiation Therapy Versus No Further Therapy in Selected Patients With Stage IB Carcinoma of the Cervix After Radical Hysterectomy and Pelvic Lymphadenectomy

Sedlis, Alexander; Bundy, Brian N.; Rotman, Marvin Z.; Lentz, Samuel S.; Muderspach, Laila I.; Zaino, Richard J. Author Information

A Randomized Trial of Pelvic Radiation Therapy versus No Further Therapy in Selected Patients with Stage IB Carcinoma of the Cervix after Radical Hysterectomy and Pelvic Lymphadenectomy: A Gynecologic Oncology Group Study

Objective.The objective of this study was to evaluate the benefits and risk of adjuvant pelvic radiotherapy aimed at reducing recurrence in women with Stage IB cervical cancer treated by radical hysterectomy and pelvic lymphadenectomy.Methods.Two hundred seventy-seven eligible patients were entered with at least two of the following risk factors: >1/3 stromal invasion, capillary lymphatic space involvement, and large clinical tumor diameter. Of 277 patients, 137 were randomized to pelvic radiotherapy (RT) and 140 to no further treatment (NFT).Results.Twenty-one (15%) in the RT group and 39 (28%) in the NFT group had a cancer recurrence, 18 of whom were vaginal/pelvic in the RT and 27 in the NFT group. In the RT group, of 18 (13%) who died, 15 died of cancer. In the NFT group, of the 30 (21%) who died, 25 died from cancer. Life table analysis indicated a statistically significant (47%) reduction in risk of recurrence (relative risk = 0.53,P= 0.008, one-tail) among the RT group, with recurrence-free rates at 2 years of 88% versus 79% for the RT and NFT groups, respectively. Severe or life-threatening (Gynecologic Oncology Group grade 3 or 4) urologic adverse effects occurred in 4 (3.1%) in the RT group and 2 (1.4%) in the NFT group; 3 (2.3%) and 1 (0.7%) hematologic; 4 (3.1%) and 0 gastrointestinal (GI); and 1 (0.8%) and 0 neurologic, respectively. One patient's death was attributable to grade 4 GI adverse effects.Conclusions.Adjuvant pelvic radiotherapy following radical surgery reduces the number of recurrences in women with Stage IB cervical cancer at the cost of 6% grade 3/4 adverse events versus 2.1% in the NFT group.

Surgically-treated early cervical cancer: Prognostic factors and the significance of depth of tumor invasion.

The objectives of this study were to scrutinize surgical features and analyze local tumor parameters of early cervical cancer to identify patients at-risk for recurrent disease. Three hundred eight patients who underwent radical hysterectomy and pelvic lymphadenectomy between 1984 and 1997 were studied retrospectively. All radical hysterectomies were performed in a referral oncology center, and treatment policies and operating staff were the same during the study period. Operating time gradually decreased significantly during the study period from an average of 270 min to an average of 187 min (P < 0.0001), and blood loss during surgery also decreased continually from 1515 ml to 1071 ml (P < 0.0001). Postoperative radiation treatment was given to 119 patients (40%). The overall five-year survival rate was 83%, 91% for those with negative, and 53% for those with positive pelvic nodes. Univariate analysis showed that lymph node status, parametrial involvement, status of the surgical margins, capillary lymphatic space involvement, tumor size and depth of invasion were all significantly related to the occurrence of recurrent disease. Multivariate analysis revealed that lymph node involvement (hazard ratio 4.4), parametrial involvement, tumor size and depth of invasion were independent factors of prognostic significance for disease-free survival. It was concluded that the local control of cervical tumors infiltrating > 10 mm (hazard ratio 5.1) might be improved by adjuvant radiotherapy, even in the absence of lymph node metastasis, parametrial involvement or affected surgical margins.

Isolated local recurrence in carcinoma of the vulva: prognosis and implications for treatment

Faul C, Miramow D, Gerszten K, Huang C, Edwards R. Isolated local recurrence in carcinoma of the vulva: Prognosis and implications for treatment. Int J Gynecol Cancer 1998; 8: 409–414. An isolated local recurrence in squamous cell carcinoma (SCC) of the vulva is reported to have a high surgical salvage rate. This study evaluates the impact of an isolated local recurrence on survival and evaluates predictive factors for outcome. Forty-seven patients were found to have an isolated local recurrence following definitive therapy for SCC of the vulva between 1980 and 1996 at a single institution. The primary and recurrent tumor's surgicopathological characteristics were retrospectively reviewed. Actuarial survival rates were calculated by the Kaplan Meier method and prognostic factors analyzed by the Cox proportional hazards model. Thirty-one patients were treated with surgery alone, 14 with combined therapy or radiation alone and two were not treated at recurrence. Actuarial 5-year survival was 40 %. Treatment modality had no influence on outcome despite having bulkier recurrences in the combination or radiation group. On univariate analysis FIGO (International Federation of Gynecology and Obstetrics) stage at initial presentation, disease free interval of < one year, pathologically positive inguinal nodes at presentation, capillary lymphatic space involvement (CLS) at presentation and tumor size at recurrence were all significant predictors for survival. On multivariate analysis CLS in primary tumor, tumor size at recurrence, and pathologically positive nodes at initial presentation reached statistical significance. There was a high subsequent local and distant recurrence rate. An isolated first local recurrence does not have a uniformly good prognosis. Avoidance of local recurrence is important. With a high subsequent local and distant recurrence rate, more innovative treatment strategies are needed.

Blood Transfusion and the Risk of Recurrence in Stage IB Cervical Cancer

The objective of this study is to determine if perioperative blood transfusions increase the risk of recurrence in stage IB cervical cancer. Medical records from all patients with FIGO stage IB cervical cancer undergoing radical hysterectomy and pelvic lymphadenectomy (RH + PLND) at the University of Iowa and the University of Nebraska from 1978 to 1990 were retrospectively reviewed. Data collected included patient age, body mass index (BMI), tumor size, cell type, depth of cervical invasion (DOI), presence of capillary-lymphatic space involvement (CLSI), lymph node metastasis, operating time, estimated blood loss, transfusion, and follow-up data. Three hundred two patients underwent RH + PLND. Transfusions were given to 244 (81%), with a mean of 2.6 units (range 1-18 units). Median follow-up was 49.5 months (range 9-190 months). Twenty patients (6.6%) had pelvic nodal metastasis. There were no periaortic nodal metastases in the 101 patients who had periaortic nodes dissected. There were no significant differences between the transfused and nontransfused groups, with respect to age, BMI, DOI, or pelvic node metastasis. Transfused patients differed significantly from the nontransfused in that they had larger tumors (P = 0.047), more frequent CLSI (P = 0.013), longer procedures (P = 0.02), and greater estimated blood loss (P < 0.0001). Recurrences developed in 29 patients (19 pelvic, 7 lung, 3 bone). There is no difference in disease-free survival (DFS) or calculated projected survival between the transfused and nontransfused groups. Pelvic node metastasis and tumor size were independent poor prognosticators. After controlling for these factors, the number of blood transfusions was not predictive of recurrence or survival. Perioperative transfusions do not increase the risk of recurrence in patients with cervical cancer.

Malignant melanoma of the vulva treated by radical hemivulvectomy. A prospective study of the gynecologic oncology group

Beginning in 1983, the Gynecologic Oncology Group (GOG) conducted a prospective clinicopathologic study of primary malignant melanoma of the vulva. The objectives of this study were to determine the relationship of histopathologic parameters and microstaging to the International Federation of Gynaecology and Obstetrics (FIGO) staging and prognosis. All patients with primary untreated malignant melanoma of the vulva and no history of previous or subsequent other primary invasive malignancy were eligible for study entry. All patients were required to have modified radical hemivulvectomy as minimal therapy. Groin dissection was optional. Histopathologic specimens were reviewed for capillary space involvement, Clark's level, Breslow's depth of invasion, cell type, and melanin distribution. Patient characteristics were analyzed in their relationship to groin node status and recurrence-free interval. Between 1983 and 1990, 81 patients were entered in the study. Of these, 71 were evaluable. Thirty-four patients underwent radical hemivulvectomy, and 37 patients underwent radical vulvectomy. In addition, 56 patients underwent groin node dissection. The factors that were independently correlated with groin node status were: capillary lymphatic space involvement (p = 0.0001) and central primary tumor location (i.e., bilateral/clitoral/T3) (P = 0.003). The other factors that were significant--clinical tumor size, vulvar staging (FIGO), GOG performance status, and Breslow's depth of invasion--were not independent predictors of positive nodes. The factor with the highest significant correlation with recurrence-free interval was the 1992 staging system of the American Joint Committee on Cancer (AJCC) for malignant melanoma of the skin. Using multiple regression, AJCC stage was the only independent prognostic factor. In the absence of AJCC stage, Breslow's depth of invasion was the most prognostic. The biologic behavior of vulvar melanoma is similar to other nongenital cutaneous malignant melanoma.

A prospective surgical pathological study of stage I squamous carcinoma of the cervix: A Gynecologic Oncology Group study

Thirty-three institutions collaborating in the Gynecologic Oncology Group gathered surgical and pathological data on 1125 patients with primary, previously untreated, histologically confirmed stage I cervical carcinoma with more than 3 mm of invasion who were selected to undergo radical hysterectomy and paraaortic and pelvic lymphadenectomy. Of the 940 eligible, evaluable patients, 732 had squamous carcinoma. Of the study group, 87 (12%) did not undergo radical hysterectomy because of gross disease beyond the uterus or microscopic aortic node involvement documented at exploratory laparotomy. Among the 645 patients undergoing pelvic and paraaortic lymphadenectomy and radical hysterectomy, five risk factors were significantly associated with microscopic pelvic lymph node metastasis: depth of invasion ( P = 0.0001), parametrial involvement ( P = 0.0001), capillary-lymphatic space invasion ( P = 0.0001), tumor grade ( P = 0.01), and gross versus occult primary tumor ( P = 0.009). The factors identified as independent risk factors for pelvic lymph node metastasis by multivariate analysis were capillary-lymphatic space involvement ( P < 0.0001), depth of invasion ( P < 0.0001), parametrial involvement ( P = 0.0005), and age ( P = 0.02). The model was used to predict the chance of a patient having nodal metastasis for any combination of risk factors.