Prognostic impact of lymph node ratio outperforms positive lymph nodes and lymph nodes harvested: a time-dependent analysis in mismatch repair-proficient and –deficient colrectal cancers

Objective: We compare the prognostic strength of the lymph node ratio (LNR), positive lymph nodes (+LNs) and collected lymph nodes (LNcoll) using a time-dependent analysis in colorectal cancer patients stratified by mismatch repair (MMR) status. Method: 580 stage III-IV patients were included. Multivariable Cox regression analysis and time-dependent receiver operating characteristic (tROC) curve analysis were performed. The Area under the Curve (AUC) over time was compared for the three features. Results were validated on a second cohort of 105 stage III-IV patients. Results: The AUC for the LNR was 0.71 and outperformed + LNs and LNcoll by 10–15 % in both MMR-proficient and deficient cancers. LNR and + LNs were both significant (p<0.0001) in multivariable analysis but the effect was considerably stronger for the LNR [LNR: HR=5.18 (95 % CI: 3.5–7.6); +LNs=1.06 (95 % CI: 1.04–1.08)]. Similar results were obtained for patients with >12 LNcoll. An optimal cut off score for LNR=0.231 was validated on the second cohort (p<0.001). Conclusion: The LNR outperforms the + LNs and LNcoll even in patients with >12 LNcoll. Its clinical value is not confounded by MMR status. A cut-of score of 0.231 may best stratify patients into prognostic subgroups and could be a basis for the future prospective analysis of the LNR.

Tamoxifen after adjuvant chemotherapy for premenopausal women with lymph node-positive breast cancer: International Breast Cancer Study Group Trial 13-93

PURPOSE: The value of adjuvant tamoxifen after chemotherapy for premenopausal women with breast cancer has not been adequately assessed. PATIENTS AND METHODS: Between 1993 and 1999, International Breast Cancer Study Group Trial 13-93 enrolled 1,246 assessable premenopausal women with axillary node-positive, operable breast cancer. All patients received chemotherapy (cyclophosphamide plus either doxorubicin or epirubicin for four courses followed by immediate or delayed classical cyclophosphamide, methotrexate, and fluorouracil for three courses), which was followed by either tamoxifen (20 mg daily) for 5 years or no further treatment. The primary end point was disease-free survival (DFS). Tumors were classified as estrogen receptor (ER) -positive (n = 735, 59%) if immunohistochemical (IHC) or ligand-binding assays (LBA) were clearly positive. The ER-negative group included all other tumors (n = 511, 41%). A subset of the ER-negative group was defined as ER absent (n = 108, 9%) if IHC staining was none or if the LBA result was 0 fmol/mg cytosol protein. The median follow-up time was 7 years. RESULTS: Tamoxifen improved DFS in the ER-positive cohort (hazard ratio [HR] for tamoxifen v no tamoxifen = 0.59; 95% CI, 0.46 to 0.75; P < .0001) but not in the ER-negative cohort (HR = 1.02; 95% CI, 0.77 to 1.35; P = .89). Tamoxifen had a detrimental effect on patients with ER-absent tumors compared with no tamoxifen in an unplanned exploratory analysis (HR = 2.10; 95% CI, 1.03 to 4.29; P = .04). Patients with ER-positive tumors who achieved chemotherapy-induced amenorrhea had a significantly improved outcome (HR for amenorrhea v no amenorrhea = 0.61; 95% CI, 0.44 to 0.86; P = .004), whether or not they received tamoxifen. CONCLUSION: Tamoxifen after adjuvant chemotherapy significantly improved treatment outcome in premenopausal patients with endocrine-responsive disease, but its use as adjuvant therapy for patients with ER-negative tumors is not recommended.

Is Pelvic Lymph Node Dissection Necessary in Patients with a Serum PSA<10ng/ml Undergoing Radical Prostatectomy for Prostate Cancer?

OBJECTIVE: Controversy persists concerning the role of pelvic lymph node dissection (PLND) in patients with preoperative PSA values <10ng/ml undergoing treatment for prostate cancer with a curative intent. The aim of this study was to determine the incidence of lymph node metastasis in this subgroup of patients. METHODS: Patients with clinically localized prostate cancer and a serum PSA<10ng/ml, without neoadjuvant hormonal or radiotherapy, with negative staging examinations who underwent radical retropubic prostatectomy with bilateral extended PLND and with >/=10 lymph nodes detected by the pathologist in the surgical specimen, were included in the study. RESULTS: A total of 231 patients with a median serum PSA of 6.7ng/ml (range 0.4-9.98) and a median age of 62 years (range 44-76) were evaluated. A median of 20 (range 10-72) nodes were removed per patient. Positive nodes were found in 26 of 231 patients (11%), the majority of which (81%) had a Gleason score >/=7 in the surgical specimen. Of the patients with a Gleason score >/=7 in the prostatectomy specimen 25% had positive nodes, whereas only 3% with a Gleason score node positive. CONCLUSIONS: The incidence of positive nodes in patients with clinically localized prostate cancer, a serum PSA<10ng/ml and a Gleason score >/=7 in the prostatectomy specimen was 25% after extended PLND. It seems that in this patient group extended PLND, including removal of nodes along the internal iliac vessels, is warranted.

Prognostic factors in lymph node metastases of prostatic cancer patients: the size of the metastases but not extranodal extension independently predicts survival

AIMS: To analyse tumour characteristics and the prognostic significance of prostatic cancers with extranodal extension of lymph node metastases (ENE) in 102 node-positive, hormone treatment-naive patients undergoing radical prostatectomy and extended lymphadenectomy. METHODS AND RESULTS: The median number of nodes examined per patient was 21 (range 9-68), and the median follow-up time was 92 months (range 12-191). ENE was observed in 71 patients (70%). They had significantly more, larger and less differentiated nodal metastases, paralleled by significantly larger primary tumours at more advanced stages and with higher Gleason scores than patients without ENE. ENE defined a subgroup with significantly decreased biochemical recurrence-free (P = 0.038) and overall survival (P = 0.037). In multivariate analyses the diameter of the largest metastasis and Gleason score of the primary tumour were independent predictors of survival. CONCLUSIONS: ENE in prostatic cancer is an indicator lesion for advanced/aggressive tumours with poor outcome. However, the strong correlation with larger metastases suggests that ENE may result from their size, which was the only independent risk factor in the metastasizing component. Consequently, histopathological reports should specify the true indicator of poor survival in the lymphadenectomy specimens, which is the size of the largest metastasis in each patient.

Extracapsular tumor spread and the risk of local, axillary and supraclavicular recurrence in node-positive, premenopausal patients with breast cancer

BACKGROUND: Extracapsular tumor spread (ECS) has been identified as a possible risk factor for breast cancer recurrence, but controversy exists regarding its role in decision making for regional radiotherapy. This study evaluates ECS as a predictor of local, axillary, and supraclavicular recurrence. PATIENTS AND METHODS: International Breast Cancer Study Group Trial VI accrued 1475 eligible pre- and perimenopausal women with node-positive breast cancer who were randomly assigned to receive three to nine courses of classical combination chemotherapy with cyclophosphamide, methotrexate, and fluorouracil. ECS status was determined retrospectively in 933 patients based on review of pathology reports. Cumulative incidence and hazard ratios (HRs) were estimated using methods for competing risks analysis. Adjustment factors included treatment group and baseline patient and tumor characteristics. The median follow-up was 14 years. RESULTS: In univariable analysis, ECS was significantly associated with supraclavicular recurrence (HR = 1.96; 95% confidence interval 1.23-3.13; P = 0.005). HRs for local and axillary recurrence were 1.38 (P = 0.06) and 1.81 (P = 0.11), respectively. Following adjustment for number of lymph node metastases and other baseline prognostic factors, ECS was not significantly associated with any of the three recurrence types studied. CONCLUSIONS: Our results indicate that the decision for additional regional radiotherapy should not be based solely on the presence of ECS.

Is adjuvant chemotherapy of benefit for postmenopausal women who receive endocrine treatment for highly endocrine-responsive, node-positive breast cancer? International Breast Cancer Study Group Trials VII and 12-93

To compare the efficacy of chemoendocrine treatment with that of endocrine treatment (ET) alone for postmenopausal women with highly endocrine responsive breast cancer. In the International Breast Cancer Study Group (IBCSG) Trials VII and 12-93, postmenopausal women with node-positive, estrogen receptor (ER)-positive or ER-negative, operable breast cancer were randomized to receive either chemotherapy or endocrine therapy or combined chemoendocrine treatment. Results were analyzed overall in the cohort of 893 patients with endocrine-responsive disease, and according to prospectively defined categories of ER, age and nodal status. STEPP analyses assessed chemotherapy effect. The median follow-up was 13 years. Adding chemotherapy reduced the relative risk of a disease-free survival event by 19% (P = 0.02) compared with ET alone. STEPP analyses showed little effect of chemotherapy for tumors with high levels of ER expression (P = 0.07), or for the cohort with one positive node (P = 0.03). Chemotherapy significantly improves disease-free survival for postmenopausal women with endocrine-responsive breast cancer, but the magnitude of the effect is substantially attenuated if ER levels are high.

Good outcome for patients with few lymph node metastases after radical retropubic prostatectomy

BACKGROUND: Conflicting results exist regarding the value of an extended pelvic lymph node dissection (PLND) in node-positive patients undergoing radical retropubic prostatectomy (RRP) for clinically localized prostate cancer. OBJECTIVE: To assess the long-term outcome in node-positive patients who underwent extended PLND followed by RRP. DESIGN, SETTING, AND PARTICIPANTS: A consecutive series of 122 node positive patients with negative preoperative staging examinations, no neoadjuvant hormonal or radiotherapy, and who underwent extended PLND (>/=10 lymph nodes in the surgical specimen) followed by RRP were analyzed. None of the patients received immediate androgen deprivation therapy (ADT). INTERVENTION: All patients underwent extended PLND followed by RRP. MEASUREMENTS: Biochemical recurrence-free survival, cancer-specific, and overall survival were assessed using the Kaplan-Meier technique. RESULTS AND LIMITATIONS: Median prostate-specific antigen (PSA) was 16ng/ml. At pathological examination 76% of the 122 patients had pT3-pT4 tumours, 50% seminal vesicle infiltration. A median of 22 nodes were removed per patient. Median cancer-specific survival at 5 and 10 yr was 84.5% and 60.1%, respectively. In patients with /=3 positive nodes removed, median cancer-specific survival at 10 yr was 78.6% and 33.4%, respectively (p<0.001). After a median period of 33 mo, 61 of the 122 patients (50%) received ADT, particularly those (69%) with >/=3 positive nodes removed. This retrospective study includes a significant percentage of patients with high tumour burden, and therefore may not reflect current patient series. CONCLUSIONS: Patients with nodes detected after extended PLND followed by RRP had good long-term results and should not be denied treatment with curative intent. In contrast, prognosis was poor in patients with >/=3 positive nodes, despite extended PLND and despite ADT in 69% of patients.

Comparison of outcome and recurrence-free survival after sentinel lymph node biopsy and lymphadenectomy in vulvar cancer

OBJECTIVES: Lymph node status is an important prognostic factor in patients with squamous cell carcinoma (SCC) of the vulva. Complete inguinofemoral lymph node dissection (ILND) is accompanied by a high morbidity. Sentinel lymph node biopsy (SLNB) was established for less invasive lymph node (LN) staging. The aim of this study was to evaluate safety of SLNB in terms of accuracy and outcome in a clinical routine setting. METHODS: We retrospectively reviewed the data of patients who underwent SLNB and/or ILND for vulvar SCC in the years 1990-2007. Clinical follow-up was evaluated for histological nodal-negative patients with tumor stage T1 or T2. The false negative rate of SLNB was determined in patients who underwent both SLNB and ILND. RESULTS: Preoperative sentinel lymph node (SLN) visualization by scintigraphy was successful in 95% of all patients. SLNB was false negative in 1/45 inguinae (2.2%). All SLN were detected intraoperatively. During the follow-up period (median 24 months for SLNB and 111 months for ILND), no groin recurrences in initially nodal negative patients occurred (n=34, 59 inguinae). Transient lymph edema occurred in 7/18 patients after ILND (39%) and 2/16 patients (13%) after SLNB. No persistent edemas were found after SLNB and ILND. CONCLUSION: According to our experience SLNB is feasible and accurately predicts LN status of vulvar SCC under clinical routine conditions. SLNB in vulvar cancer seems to be a safe alternative to ILND in order to reduce morbidity of surgical treatment.