Risk Of Local Disease Recurrence Research Articles

Narrative review of the application of radiotherapy in nipple-areola-complex–sparing mastectomy

: In the treatment of breast cancer, the effective removal of the tumor was once the sole aim of surgery. However, the goals of breast cancer surgery have shifted, with considerable emphasis now placed on improving the appearance and function of the breast while leaving the curative effect unaffected or even improved. Nipple-areola-complex-sparing mastectomy (NSM) facilitates breast reconstruction by preserving the skin and nipple-areola complex (NAC) of the breast. In recent years, this approach has become increasingly popular; however, it still carries a high risk of local recurrence in the NAC. Therefore, for patients who NSM, adjuvant radiotherapy (RT) is recommended. Although adjuvant radiation therapy is the standard of care for breast cancer treatment following lumpectomy, the application of RT after NSM is controversial. Previous studies on the roles of pre-, intra-, and/or postoperative RT combined with NSM have produced inconsistent results. Conventional preoperative or postoperative RT for breast cancer can cause contracture deformation of the implanted prosthesis. The emergence of intraoperative RT technology has further optimized radiotherapy-assisted NSM combined with breast reconstruction as a therapeutic strategy for breast cancer. The main complications of this treatment include fat necrosis, radiation fibrosis, and prosthesis contracture. Based on the selection of suitable patients, adjuvant RT is applied in combination with NSM according to the risk of local disease recurrence. In this article, we review the application of RT in NSM and compare studies on NSM combined with pre-, intra-, and/or postoperative RT.

Imaging assessment of local recurrence of prostate cancer after radical prostatectomy.

Definitive therapy for prostate cancer includes radical prostatectomy and radiation therapy. Treatment is elected based on patient preference, biological tumor factors, and underlying health. Post prostatectomy, men are surveyed for disease recurrence with serial PSA measurements, digital rectal exam, and imaging studies depending on nomogram predicted risk of local disease recurrence and distant metastasis. In men with rising PSA levels, pathologically incomplete surgical margins or, if symptoms of metastasis develop, imaging may be obtained to localize disease. In cases of known biochemical recurrence, imaging is used to target biopsy, to contour in salvage radiation therapy and to assess disease response. For local disease recurrence, the most commonly performed exams are pelvic MRI and transrectal US. CT can evaluate for lymph node metastasis, but is suboptimal in the evaluation of the prostatectomy bed. PET/CT and PET/MRI have been used successfully to evaluate for local disease recurrence. The PI-RADSv2.1 manual provides a risk level and lexicon for use in description of prostate carcinoma prior to prostatectomy, but does not address imaging features post-surgery. A detailed description of nodal, bony, and visceral metastasis is given elsewhere. This manuscript outlines the context in which appropriate imaging exams may be obtained and focuses on imaging findings concerning for local disease recurrence after prostatectomy on various imaging modalities including CT, US, MRI, and PET.

Targeted sequencing and intracranial outcomes of patients with lung adenocarcinoma brain metastases treated with radiotherapy.

Treatment for advanced lung adenocarcinoma (AC) has become increasingly personalized based on molecular results. However, for patients with AC brain metastases (BMs), intracranial outcomes based on molecular subtype and the frequency of molecular aberrations are less well defined. This study sought to report targeted next-generation sequencing results and investigate molecularly based outcomes for patients with AC-BMs treated with radiotherapy. The records of 132 patients with AC-BMs treated at Emory University from September 2008 to August 2016 with successful next-generation sequencing were reviewed. Rates of local disease recurrence, distant brain failure (DBF), and salvage whole-brain radiotherapy (WBRT) were estimated using cumulative incidence with competing risk analysis. Univariate and multivariate analyses were performed. The most common aberrations included tumor protein 53 (TP53) (60%), KRAS (29%), epidermal growth factor receptor (EGFR) (20.5%), phosphatase and tensin homolog (PTEN) loss (15.5%), and MET amplification (13%). The majority of patients (62%) were treated with stereotactic radiosurgery alone. In these patients, KRAS mutation, anaplastic lymphoma kinase (ALK) rearrangement, and having ≥ 6 BMs were associated with an increased risk of salvage WBRT (P < .05). KRAS mutation remained significant for an increased risk of salvage WBRT when compared with EGFR/ALK/KRAS-negative patients (hazard ratio, 5.17; P < .05), despite a similar risk of DBF. PTEN loss was associated with increased risk of DBF (P < .05), whereas EGFR and ALK aberrations were associated with a decreased risk of local disease recurrence (P < .05). The results of the current study quantified the frequency of genetic aberrations in patients with AC-BMs and demonstrated their association with intracranial outcomes. In particular, a cohort of patients with KRAS mutations and ≥6 BMs were identified to be at high risk of requiring salvage WBRT after undergoing upfront stereotactic radiosurgery.

Risk factors for locoregional disease recurrence after breast-conserving therapy in patients with breast cancer treated with neoadjuvant chemotherapy: An international collaboration and individual patient meta-analysis.

Several studies have reported a high risk of local disease recurrence (LR) and locoregional disease recurrence (LRR) in patients with breast cancer after neoadjuvant chemotherapy (NCT) and breast-conserving therapy (BCT). The objective of the current study was to identify potential risk factors for LR and LRR after NCT and BCT. Individual patient data sets from 9 studies were pooled. The outcomes of interest were the occurrence of LR and/or LRR. A 1-stage meta-analytic approach was used. Cox proportional hazards regression models were applied to identify factors that were predictive of LR and LRR, respectively. A total of 9 studies (4125 patients) provided their data sets. The 10-year LR rate was 6.5%, whereas the 10-year LRR rate was 10.3%. Four factors were found to be associated with a higher risk of LR: 1) estrogen receptor-negative disease; 2) cN + disease; 3) a lack of pathologic complete response in axilla (pN0); and 4) pN2 to pN3 disease. The predictive score for LR determined 3 risk groups: a low-risk, intermediate-risk, and high-risk group with 10-year LR rates of 4.0%, 7.9%, and 20.4%, respectively. Two additional factors were found to be associated with an increased risk of LRR: cT3 to cT4 disease and a lack of pathologic complete response in the breast. The predictive score for LRR determined 3 risk groups; a low-risk, intermediate-risk, and high-risk group with 10-year LRR rates of 3.2%, 10.1%, and 24.1%, respectively. BCT after NCT appears to be an oncologically safe procedure for a large percentage of patients with breast cancer. Two easy-to-use clinical scores were developed that can help clinicians to identify patients at higher risk of LR and LRR after NCT and BCT and individualize the postoperative treatment plan and follow-up. Cancer 2018;124:2923-30. © 2018 American Cancer Society.

Patient views and correlates of radiotherapy omission in a population-based sample of older women with favorable-prognosis breast cancer.

The omission of radiotherapy (RT) after lumpectomy is a reasonable option for many older women with favorable-prognosis breast cancer. In the current study, we sought to evaluate patient perspectives regarding decision making about RT. Women aged 65 to 79 years with AJCC 7th edition stage I and II breast cancer who were reported to the Georgia and Los Angeles County Surveillance, Epidemiology, and End Results registries were surveyed (response rate, 70%) regarding RT decisions, the rationale for omitting RT, decision-making values, and understanding of disease recurrence risk. We also surveyed their corresponding surgeons (response rate, 77%). Patient characteristics associated with the omission of RT were evaluated using multilevel, multivariable logistic regression, accounting for patient clustering within surgeons. Of 999 patients, 135 omitted RT (14%). Older age, lower tumor grade, and having estrogen receptor-positive disease each were found to be strongly associated with omission of RT in multivariable analyses, whereas the number of comorbidities was not. Non-English speakers were more likely to omit RT (adjusted odds ratio, 5.9; 95% confidence interval, 1.4-24.5). The most commonly reported reasons for RT omission were that a physician advised the patient that it was not needed (54% of patients who omitted RT) and patient choice (41%). Risk of local disease recurrence was overestimated by all patients: by approximately 2-fold among those who omitted RT and by approximately 8-fold among those who received RT. The risk of distant disease recurrence was overestimated by approximately 3-fold on average. To some extent, decisions regarding RT omission are appropriately influenced by patient age, tumor grade, and estrogen receptor status, but do not appear to be optimally tailored according to competing comorbidities. Many women who are candidates for RT omission overestimate their risk of disease recurrence. Cancer 2018;124:2714-2723. © 2018 American Cancer Society.

Impact of surgical resection extension on outcome for primary well-differentiated thyroid cancer\u2014a retrospective analysis

BackgroundThe surgical resection extension in well-differentiated thyroid cancer is controversially discussed with the possibility of an overtreatment on the one hand against the risk of local disease recurrence. The aim of this study is to evaluate how the surgical resection extension with the adjunction of radioiodine therapy affects postoperative morbidity and the oncologic outcome of patients primarily treated for well-differentiated thyroid cancer.MethodsAll patients undergoing primary surgery for a well-differentiated, non-recurrent thyroid cancer from January 2005 to April 2013 at Tuebingen University Hospital were retrospectively analyzed.ResultsPapillary thyroid cancer (PTC) was present in 73 patients (including 27 papillary microcarinoma) and follicular thyroid cancer in 14 patients. Fifty-six of 87 patients (64%) underwent one-stage surgery, of which 26 patients (30%) received simultaneous lymph node dissection (LND). The remaining 31 patients (36%) underwent a two-stage completion surgery (29 patients with LND). Only in three patients a single lymph node metastasis was newly detected during two-stage completion surgery. Patients with LND at either one-stage and two-stage completion surgery had a significant higher rate of transient postoperative hypocalcemia.Postoperative adjuvant radioiodine therapy was performed in 68 of 87 patients (78%). After a median follow-up of 69 months [range 9–104], one local recurrence was documented in a patient suffering from PTC 23 months after surgery.ConclusionNo prophylactic two-stage lymphadenectomy should be performed in case of well-differentiated thyroid cancer to avoid unnecessary complication without any proven oncologic benefit.

PD73-08 THE IMPACT OF INTRA VS. POST-OPERATIVE BLOOD TRANSFUSION ON CANCER RECURRENCE AND SURVIVAL FOLLOWING NEPHRECTOMY FOR RENAL CELL CARCINOMA

You have accessJournal of UrologyKidney Cancer: Localized: Surgical Therapy VII1 Apr 2017PD73-08 THE IMPACT OF INTRA VS. POST-OPERATIVE BLOOD TRANSFUSION ON CANCER RECURRENCE AND SURVIVAL FOLLOWING NEPHRECTOMY FOR RENAL CELL CARCINOMA Yasmin Abu-Ghanem, Zohar Dotan, Issac Kaver, Dorit Zilberman, and Jacob Ramon Yasmin Abu-GhanemYasmin Abu-Ghanem More articles by this author , Zohar DotanZohar Dotan More articles by this author , Issac KaverIssac Kaver More articles by this author , Dorit ZilbermanDorit Zilberman More articles by this author , and Jacob RamonJacob Ramon More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.3201AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The effects of perioperative blood transfusion (PBT) on morbidity, mortality following cancer surgery have previously been demonstrated in several malignancies including renal cell carcinoma (RCC). However, the significance of transfusion timing is still unclear. The purpose of this study is to evaluate whether intraoperative BT (InBT) differ from postoperative BT (PoBT) in regards to oncological outcomes in patients treated with nephrectomy for RCC. METHODS Study included 1159 patients with RCC who underwent radical (RN) or partial nephrectomy (PN) between 1988 and 2013. PBT was defined as receipt of packed red blood cells either during surgery or during the postsurgical hospitalization. Univariate and multivariate models were used to evaluate the association of BT with cancer-specific survival (CSS), disease-free survival (DFS) and overall survival (OS). RESULTS Of 1159 patients undergoing nephrectomy, 198 patients (17.1%) received a PBT. Patients were next divided into 3 groups; no PBT, InBT alone (n=117) and PoBT alone (n=60). Twenty one patients of the PBT group (10.6%) received both intra and post-operative transfusion. Given the small number of patients, this sub-group was excluded. On multivariate analyses, receipt of InBT was associated with significantly increased risk of local disease recurrence (HR: 2.3; P=0.025), metastatic progression (HR: 2.2; P=0.006), cancer- specific mortality (HR: 2.95; P=0.009) and all-cause mortality (HR: 2.05; P=0.007); while receipt of a PoBT did not independently bear an increased risk of local recurrence (p = 0.1), metastatic progression (P=0.095) or kidney cancer death (P=0.53), yet did significantly increase the risk of overall mortality (HR: 2.6; P=0.002). CONCLUSIONS In the current cohort, InBT but not PoBT was associated with significantly increased risk of cancer recurrence and cancer-specific mortality. This observation requires further studies to assess the impact and management of more restrictive intraoperative blood management strategies. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1370 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Yasmin Abu-Ghanem More articles by this author Zohar Dotan More articles by this author Issac Kaver More articles by this author Dorit Zilberman More articles by this author Jacob Ramon More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

A multi-institutional analysis of peritransplantation radiotherapy in patients with relapsed/refractory Hodgkin lymphoma undergoing autologous stem cell transplantation.

No consensus exists regarding the use of radiotherapy (RT) in conjunction with high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) for patients with relapsed/refractory classical Hodgkin lymphoma (HL). The objectives of the current study were to characterize practice patterns and assess the efficacy and toxicity of RT at 2 major transplantation centers. Eligible patients underwent HDC/ASCT from 2006 through 2015 using the combination of either carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM) or cyclophosphamide, BCNU, and etoposide (CBV). For the cohort of 189 patients, the 4-year overall survival rate was 80%, the progression-free survival rate was 67%, and the local control (LC) rate was 68%. RT was used within 4 months of ASCT for 22 patients (12%) and was given more often for disease that was early stage, primary refractory, or [18 F]fluorodeoxyglucose (FDG)-avid at the time of HDC/ASCT. Disease recurrence occurring after HDC/ASCT was associated with primary refractory disease and FDG-avidity at the time of HDC/ASCT. RT was not found to be associated with LC, progression-free survival, or overall survival on univariate analysis. In a model incorporating primary refractory HL and FDG-avid disease at the time of HDC/ASCT, RT was found to be associated with a decreased risk of local disease recurrence (hazard ratio, 0.3; P = .02). In patients with primary refractory HL and/or FDG-avid disease at the time of HDC/ASCT, the 4-year LC rate was 81% with RT versus 49% without RT (P = .03). There was one case of Common Terminology Criteria for Adverse Events grade ≥ 3 RT-related toxicity (acute grade 3 pancytopenia). In patients undergoing ASCT for relapsed/refractory HL, peritransplantation RT was used more often for disease that was early stage, primary refractory, or FDG-avid after salvage conventional-dose chemotherapy. RT was associated with improved LC of high-risk localized disease and was well tolerated with modern techniques. Cancer 2017;123:1363-1371. © 2016 American Cancer Society.

Risk of recurrence of ductal carcinoma in situ by oncotype Dx technology: Some concerns

Predicting which patients with ductal carcinoma in situ (DCIS) will develop local disease recurrence: we have been trying to do that for 30 years. But now we can. The Holy Grail has been recovered in the form of Oncotype Dx, or so we have been told.1 A single genetic test capable of identifying the risk of local disease recurrence after breast conservation in patients with mammographically detected DCIS would obviate the need to factor in DCIS grade, size, and margin width, and patient age. The Oncotype Dx DCIS gene signature assay was validated in a registration trial2 that strictly defined a permissible size of ≤25 mm for low-to-intermediate grade tumors and ≤10 mm for high-grade tumors and those with margin widths of ≥3 mm. Unfortunately, most medical oncologists ordering the Oncotype Dx DCIS assay do not appreciate the limitations of the validated results. They order the $4000 test for patients with DCIS of all sizes and all margin widths. The test, if valid, is only valid if the strict protocol required of the Eastern Cooperative Oncology Group (ECOG) E5194 trial is adhered to. A transected DCIS is likely to recur in spite of a low score on the Oncotype Dx assay. A recent example of a 46-year-old woman with a low-risk Oncotype Dx score had 42 mm of disease and 3-mm margins. Her DCIS grade was intermediate with focal necrosis. A Van Nuys Prognostic Index calculation3 results in a total score of 9 (grade score of 2, size score of 3, margin score of 2, and age score of 2). Oncotype Dx provided a 10-year risk of disease recurrence of 15%, whereas the University of Southern California/Van Nuys Prognostic Index projects a local recurrence risk of 40% to 50% without irradiation. The Oncotype Dx assay is in essence a grading system based on gene expression, and is comparable to histologic grading of DCIS. Because it does not factor in a variety of important predictive factors such as age, margin width, extent of DCIS, nuclear grade, and necrosis, it is not likely to be accurate for the majority of patients. No single test, especially one in which other prognostic factors are ignored, can validly estimate the risk of local recurrence among patients with DCIS. The authors made no disclosures. Michael D. Lagios, MD1 Melvin J. Silverstein, MD2 1The Breast Cancer Consultation Service, Tiburon, California 2Department of Breast Surgery, Hoag Memorial Hospital Presbyterian, Newport Beach, California

Neoangiogenesis in Temporal Bone Carcinoma

Temporal bone squamous cell carcinoma (SCC) accounts for less than 2% of all head and neck tumors. Its biologic parameters should be investigated because clinicopathologic factors are often inaccurate for the purposes of its prognosis. CD105 is a proliferation-associated protein expressed in angiogenic endothelial cells and a potential prognostic indicator for several solid malignancies. The present study is the first to investigate the prognostic role of CD105 expression in temporal bone SCC. Retrospective clinicopathologic investigation. Tertiary referral centers. Twenty consecutive operable patients with temporal bone SCC. CD105 immunohistochemical expression in primary temporal bone SCCs was assessed using image analysis. CD105 expression was correlated with conventional clinicopathologic and prognostic parameters. Using the revised Pittsburgh staging system, T and stage correlated with local recurrence rate (p = 0.0001 and p = 0.0001, respectively) and disease-free survival (p = 0.043 and p = 0.018, respectively). The recurrence rate was significantly higher (p = 0.038) and the disease-free survival shorter in patients with CD105 expression of 9.44% or higher (p = 0.038) than in cases where it was less than 9.44%. The crude carcinoma recurrence risk ratio of was 5.9 times higher for patients whose CD105 expression was 9.44% or higher. CD105 expression in activated endothelial cells of temporal bone SCC can be considered potentially useful for detecting patients at a higher risk of local disease recurrence after treatment. Further investigations are needed to ascertain the feasibility of incorporating targeted anti-CD105 therapy in multimodality or multitarget strategies for temporal bone SCC treatment.

Mammographic density and the risk of breast cancer recurrence after breast‐conserving surgery

Women with invasive breast cancer who are treated with breast-conserving surgery and radiotherapy face a cumulative risk of local disease recurrence of approximately 10% at 10 years. To the authors' knowledge, the role of mammographic density as a risk factor for the development of local recurrence has not been thoroughly evaluated to date. Medical records were reviewed for 335 patients who underwent breast-conserving surgery for invasive breast cancer and for whom a pretreatment mammogram was available. Information was recorded concerning mammographic density as well as tumor features, patient characteristics, and adjuvant treatments received. Patients were categorized for mammographic density based on the Wolfe classification as either low (<25% density), intermediate (25-50% density), or high (>50% density). A multivariate survival analysis was conducted using the Cox proportional hazards model with local disease recurrence as the primary endpoint. Patients in the high mammographic density group experienced a much greater risk of local disease recurrence compared with women with the least dense breasts (10-year actuarial risks: 21% vs 5%; hazards ratio [HR], 5.7 [95% confidence interval, 1.6-20; P=.006]). The difference in the rates of disease recurrence at 10 years was pronounced for women who did not receive radiotherapy (40% vs 0% for patients with >50% density and <25% density, respectively; P<.0001). Mammographic breast density is an important risk factor for local breast cancer recurrence among women not receiving breast irradiation. Mammographic density should be taken into consideration when stratifying patients for clinical trials of partial breast radiotherapy. If confirmed, mammographic density might be used to help determine which patients might benefit from radiotherapy.

Toxicity, Recurrence and Survival after Adjuvant Radiotherapy Treatment for FIGO Stage I Cancer of the Endometrium

We conducted a retrospective observational study to determine the rate of toxicity, pattern of tumour recurrence and survival associated with radiotherapy treatment for FIGO stage I cancer of the endometrium. All patients had undergone definitive surgery and had been referred to the oncology department of the University Hospital Birmingham, U.K. Two hundred and forty-five women were included in the study; 228 patients were treated with radiotherapy; 160 had external beam radiation alone; 32 had vaginal vault brachytherapy alone; 36 patients had both modalities; and 17 patients were not given radiotherapy. There were nine cases of Grade 3 and 4 radiation reactions, of which four were acute, four were late and one was acute and late toxicity. The severity of both acute and late radiation effects was significantly associated with the delivery of vault brachytherapy (external beam radiotherapy alone compared with brachytherapy alone (1/158 vs 3/32; P = 0.02). Thirty-four patients were diagnosed with tumour recurrence (11 distant, 14 local, 4 patients had both distant and local disease and 5 patients had recurrence diagnosed at the time of death). Patients who received no radiotherapy were at greater risk of local pelvic tumour recurrence (P < 0.0001; hazard ratio [HR] 9.6, 95% confidence interval (CI) 3.5-26.3). Vaginal vault brachytherapy had no discernible effect on the pattern of tumour recurrence. Forty-six patients died during the follow-up period, 28 of these were attributable to carcinoma of the endometrium. There was no difference in survival between the four treatment groups (P = 0.68). The overall 5-year survival rate in our study group was 89.6% (85.4-93.8%). In a proportional hazards model, tumour grade (HR 2.0 per level [1.25, 3.17]; P = 0.004]) and age (HR 1.74 per 10 years [1.12, 2.69]; P = 0.01) were the only factors found to have an independent influence on survival. This study suggests that, although pelvic radiation may not alter overall survival, it does reduce the risk of local disease recurrence. In this study population, vaginal vault brachytherapy using a vaginal stock/dobbie showed no additional benefits compared with external beam radiotherapy; it was, however, associated with a higher rate of both acute and late radiation effects.

Underutilization of mammography in older breast cancer survivors.

Annual mammography is recommended for all breast cancer survivors. To elucidate mammography use among older survivors of breast cancer and to explore determinants of such use. Retrospective cohort study using data from the Surveillance, Epidemiology, and End Results (SEER) registry linked to Medicare claims. A cohort of 3885 breast cancer survivors aged > or =65 years diagnosed with early-stage breast cancer in the United States in 1991. Medicare mammogram claims during the 2-year period following initial breast cancer treatment. Overall, 62% of the cohort underwent annual mammography, 23% underwent mammography in 1 of 2 years, and 15% had no mammography claim in the 2 years evaluated. Twenty-two percent of the women who underwent breast-conserving surgery (BCS) without radiotherapy had no mammogram in the 2-year period evaluated, compared with 17% of those who underwent mastectomy and 4% of those who underwent BCS with radiotherapy. In multivariate analyses controlling for age, cancer stage, and other patient factors, the use of annual mammography was significantly lower among women treated with mastectomy or BCS without radiotherapy than among women treated with BCS with radiotherapy. Mammography is underused in the follow-up care of older breast cancer survivors. Underuse is of particular concern in women treated with BCS without radiotherapy because of the high risk of local disease recurrence. It is unknown whether poorer follow-up care contributes to the previously described lower rate of long-term survival among women who received this therapy.

Interobserver reproducibility of the Lagios nuclear grading system for ductal carcinoma in situ

Several studies have shown an association between high nuclear grade or necrosis of ductal carcinoma in situ (DCIS) lesions and the risk of local disease recurrence in patients with DCIS treated surgically with less than mastectomy. Although criteria for separating low from high nuclear grade lesions have been published, no information exists regarding interobserver reproducibility (IR). To assess IR in the classification of DCIS, six surgical pathologists from four institutions used the Lagios grading system to grade 125 DCIS lesions. Before meeting to evaluate the cases, a training set of 12 glass slides, including cases chosen to present conflicting cues for classification, was mailed to the participants with a written criteria summary. This was followed by a working session in which criteria were reviewed and agreed on. The pathologists then graded the lesions independently. The area of interest was marked on each slide before grading. After initial grading, the pathologists met again to resolve discrepant lesion classifications. A complete agreement among raters was achieved in 43 (35%) cases, with five of six raters agreeing in another 45 (36%) cases. In no case did two raters differ by more than one grade. The pairwise κ agreement values ranged from fair to substantial (0.30 to 0.61). Generalized κ value indicated moderate agreement (0.46, standard error = 0.02). κ statistics for the distinction between grades 1 and 2 and 2 and 3 were 0.29 and 0.48, respectively, (standard error = 0.02). Only one of the six raters differed significantly in scoring. With adherence to specific criteria, IR in the classification of DCIS cases can be obtained in most cases. Although these pathologists made a few grading system modifications, further refinements are needed, especially if grading will influence future therapy.