OBJECTIVES:To evaluate the clinical performance of an extended HPV genotyping assay for anal cancer screening in high-risk populations and investigate the prevalence of high-risk HPV (HR-HPV) genotypes in patients diagnosed with anal intraepithelial neoplasia grade 2 or worse (AIN2+). STUDY DESIGN:A prospective cohort study was conducted at the European Institute of Oncology, Milan, Italy, from September 2022 to September 2024. A total of 202 high-risk individuals were enrolled. Anal samples were collected using a brush in ThinPrep PreservCyt from all subjects for HPV testing and genotyping; cytology was performed unless histology was already available. Associations between variables and sex were tested. Sensitivity, specificity, and predictive values for AIN2+ relative to HPV status were calculated. HR-HPV genotype prevalence was analysed in the overall population and among AIN2+ cases. RESULTS:The final study population comprised 192 subjects due to 10 invalid samples. No significant associations were found between patient characteristics and sex. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 87.7 % (95 % CI: 76.3-94.9), 72.6 % (95 % CI: 64.3-79.9), 57.5 % (95 % CI: 46.4-68.0), and 93.3 % (95 % CI: 86.7-97.3), respectively. Approximately 30 % of subjects were diagnosed with AIN2+. HR-HPV genotype distribution was similar between women and men. HPV16 was predominant in AIN2+ cases (>70 %), followed by the 33/58 and 56/59/66 pools in women. CONCLUSIONS:Extended HPV genotyping may support anal cancer screening strategies by providing a potential standalone tool for both screening and triage. Further studies are needed to confirm these findings in larger cohorts.

The role of prophylactic primary tumor resection (PTR) in patients with small intestinal neuroendocrine tumors (SI-NETs) and unresectable liver metastases is a matter of debate. We aimed to evaluate outcomes in patients with SI-NETs who underwent PTR, according to the presence of metastasis and symptoms from primary. Data from patients who underwent PTR for SI-NETs from a single referral center (2007–2023) were prospectively collected. Patients were divided into three groups: non-metastatic (M0) and metastatic with primary tumor-related symptoms (MS) or metastatic asymptomatic (MA). Kaplan–Meier curves for overall survival (OS) and event-free survival (EFS) were generated and compared by group. Univariate and multivariable Cox regression analyses were performed to assess the significance of risk factors. Of 147 patients, 53 were M0, 23 were MS, and 71 were MA. Median follow-up was 26 months. The 5- and 10-year OS estimates were 100

Assessing lymph node metastasis is crucial in determining the optimal therapeutic approach for endometrial cancer (EC). Considering the impact of lymphadenectomy, there is an urgent need for a cost-effective and easily applicable method to evaluate the risk of lymph node metastasis in cases of sentinel lymph node (SLN) biopsy failure. This retrospective monocentric study enrolled EC patients, who underwent surgical staging with nodal assessment. Data concerning demographic, clinicopathological, ultrasound, and surgical characteristics were collected from medical records. Ultrasound examinations were conducted in accordance with the IETA statement. We identified 425 patients, and, after applying exclusion criteria, the analysis included 313 women. Parameters incorporated into the nomogram were selected via univariate and multivariable analyses, including platelet count, myometrial infiltration, minimal tumor-free margin, and CA 125. The nomogram exhibited good accuracy in predicting lymph node involvement, with an AUC of 0.88. Using a cutoff of 10% likelihood of nodal involvement, the nomogram displayed a low false-negative rate of 0.04 (95% CI 0.00–0.19) in the training set. The adaptability of this straightforward model renders it suitable for implementation across diverse clinical settings, aiding gynecological oncologists in preoperative patient evaluations and facilitating the design of personalized treatments. However, external validation is mandatory for confirming diagnostic accuracy.

Introduction/BackgroundSerous borderline ovarian tumors (sBOT) are associated with good prognosis and can be safely treated with fertility-sparing surgery (FSS) in order to preserve endocrine and reproductive function, even if the risk of recurrence or progression is well described. Recurrences occur more frequently in the advanced stages, but little is known about their management. In this retrospective study, we report the largest single-center series of advanced sBOT who underwent multiple FSS with a long-term follow-up, with particular emphasis on the prognostic factors.MethodologyWomen aged < 45 years old treated by FSS for sBOT FIGO stage II and III from February 1997 to July 2023, were collected. All women underwent a quarterly sonographic follow-up and dosage of Ca125 for the first two years, and every six months thereafter. They were followed at our institutions by the same expert sonographers.ResultsHundred patients with advanced-stage sBOT performed FSS. The median age was 29.3 years (range 17–43) and the median follow-up time was 111.5 months (range 65.2, 180.7). Fifteen patients had invasive implants, and 28 had microinvasion. We observed 113 relapses in 73 patients: 36% with one relapse, 22% with two, 9% with three, and 4% and 2% with 4 and 5 relapses respectively. Progression to low-grade serous tumors was observed in 7 patients, and the overall survival of the whole series was 95%. The relapse risk was high in the first 48 months, while the time lapse between relapses doubled. We observed 35 pregnancies with 30 live births and 5 miscarriages. In the univariate analysis, only the largest diameter of the lesion was statistically significant for the relapse risk.ConclusionFSS is feasible in advanced sBOT without compromising overall survival. Multiple FSS provide increasing disease-free intervals.DisclosuresThe authors declare that they have no conflict of interest.

Purpose Pre-operative diagnosis and staging of small intestine neuroendocrine tumors (SI-NETs) remain sub-optimal, with open palpation during surgery still considered the gold standard. This limits a standardized implementation of minimally invasive surgery (MIS). The aim of this single-center retrospective study was to assess a tailored diagnostic work-up to identify candidates at low risk of undetected disease who may benefit from MIS. Methods Patients diagnosed with SI-NETs between 2013 and 2022 who underwent contrast-enhanced computed tomography enterography (CTE) and Ga68-DOTATOC-positron emission tomography-CT (68 Ga DOTATATE PET/CT) preoperatively and subsequently underwent open surgical resection were included. Imaging studies were reassessed by two radiologists. Combined use of CTE and 68 Ga DOTATATE PET/CT in determining primary lesion disease burden (number of lesions) and LN disease stage (distal and proximal relative to superior mesenteric vessels) was assessed, using surgical reports and pathology as gold standard. Results Overall, 56 patients were included. Sensitivity of CTE and 68 Ga DOTATATE PET/CT for at least one primary SI-NET was 100% and 94%, respectively. In the presence of concordance between studies, combined use of CTE and 68 Ga DOTATATE PET/CT for detection of single primary tumors improved specificity to 89% ( n = 25/28) with a positive predictive value of 87.5% ( n = 21/24). Distal LN disease was identified in 89.2% of cases ( n = 33/37). The association of single lesion and distal LN disease was found pre-operatively in 32% of patients ( n = 18). Conclusion Combined use of CTE and 68 Ga DOTATATE PET/CT enables identifying low-risk surgical candidates (single SI-NET lesions with distal LN disease).

The impact of multiple infections on the risk of cervical lesions is a subject of ongoing debate. This study aims to explore whether the richness of HPV genotype infections and the biodiversity of squamous and glandular cervical dysplasias could influence the progression of precancerous lesions. We conducted a cross-sectional analysis involving 469 women who attended the Colposcopy Unit at the European Institute of Oncology in Milan, Italy, from December 2006 to December 2014. HPV type richness was measured as the number of different genotypes per patient. We calculated the associations between richness and age, as well as histologic grade, along with Simpson’s biodiversity index for cervical dysplasias. We observed significant inverse relationships between the richness of high-risk (HR) genotypes and both age (p = 0.007) and histologic grade (p < 0.001). Furthermore, as the histologic grade increased, the mean biodiversity index of cervical dysplasias decreased, with exceptions noted in cases of normal histology and adenocarcinoma in situ. Different histologic grades formed five clusters with distinct mean ages and mean biodiversity indices. These findings suggest that HPV genotype richness and the biodiversity of cervical dysplasias may play a crucial role in predicting the risk of high-grade cervical lesions, enabling personalized management of precancers.

Colposcopic patterns of Vaginal Intraepithelial Neoplasia (VAIN) are not definitively related to histological grade. The aim of the present study was to investigate any correlation between clinical and colposcopic features and the development of high-grade VAIN. Two hundred and fifty-five women diagnosed with VAIN (52 VAIN1, 55 VAIN2 and 148 VAIN3) at the European Institute of Oncology, Milan, Italy, from January 2000 to June 2022, were selected for a retrospective analysis. Multivariate logistic regression was performed to estimate the association of risk factors and colposcopic patterns with VAIN grade. Smoking was associated with the development of VAIN (34.1%, p = 0.01). Most women diagnosed with VAIN3 (45.3%, p = 0.02) had a previous history of hysterectomy for CIN2+. At multivariate analysis, colposcopic grade G2 (OR = 20.4, 95%CI: 6.67–61.4, p < 0.001), papillary lesion (OR = 4.33, 95%CI: 1.79–10.5, p = 0.001) and vascularity (OR = 14.4, 95%CI: 1.86–112, p = 0.01) were significantly associated with a greater risk of VAIN3. The risk of high-grade VAIN should not be underestimated in women with a history of smoking and previous hysterectomy for CIN2+, especially when colposcopic findings reveal vaginal lesions characterized by grade 2, papillary and vascular patterns. Accurate diagnosis is crucial for an optimal personalized management, based on risk factors, colposcopic patterns and histologic grade of VAIN.

Fertility-sparing treatment (FTS) of endometrial cancer (EC) has a high rate of remission but also a high rate of relapse (10–88%). Many women still wish to conceive at the time of relapse, but results regarding retreatment are still lacking. This study aims to evaluate the safety, oncological and pregnancy outcomes of repeated FST in women with recurrent EC. This is a retrospective single-center study that recruited patients who had uterine recurrence after achieving a complete response (CR) with FST for FIGO stage IA, well-differentiated (G1), endometrioid EC. All eligible women underwent a second FST. Among 26 patients with recurrence, 6 decided to receive a hysterectomy and 20 received fertility-sparing retreatment. In total, 17 out of 20 women (85%) achieved a CR in a median time of 6 months. A total of 2/20 women showed a stable disease and continued the treatment for a further 6 months and finally achieved a CR. In total, 1/20 women showed disease progression and underwent demolitive surgery. After relapse and a CR, 14 patients attempted to become pregnant, among whom 7 became pregnant (pregnancy rate 50%—life birth rate 29%). Secondary FST is a safe and effective option for women who desire to preserve fertility after the recurrence of early-stage EC.

Background. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a well-established diagnostic procedure for evaluating hilar and mediastinal lymphadenopathies and is the gold standard for lung cancer diagnosis and staging. Recent studies assessed the effectiveness of the 19-G flex needle in obtaining larger EBUS-TBNA samples, and prospective small series gave similar results in terms of diagnostic yield when testing different gauge needles. The lack of homogeneity between series and the small sample size of some prospective cohorts poses a limit to the validity of those results. This prospective controlled study compared the 19-G flex and 22-G needles in terms of diagnostic yield. An objective laboratory method was used to count cells and compare the two needles’ cytologic yields. Material. A prospective controlled study was conducted on 90 patients undergoing EBUS-TBNA for the diagnosis of hilar and mediastinal lymphadenopathies. The institutional ethic committee (IEO573) approved the study, and informed consent was obtained from all patients. Results. A total of 90 patients were enrolled in this study, 84.4% of whom were diagnosed with malignancy and 15.6% with non-neoplastic disease. Sensitivity for malignancy was 93.4% (CI: 87.4–97.1%) for the 19-G needle and 92.6% (CI: 86.3–96.5%) for the 22-G needle (p = 0.80). The percentage of malignant cells in the cell block was 63.9% and 61.5% for the 22-G and 19-G needles, respectively. The cell count assessed by flow cytometry was 2071 cells/µL (IQR: 600,2265) with the 22-G needle and 2761 cells/µL (IQR: 505,3250) with the 19-G needle (p = 0.79). The malignant cell count was 0.05 × 103 cells/µL with the 22-G and 0.08 × 103 cells/µL with the 19-G needle (p = 0.70). There was no difference in the presence of tissue cores in the samples, and rapid on-site evaluation (ROSE) cellularity was comparable between the two needles. Conclusions. The 19-G flex EBUS-TBNA needle is comparable to the 22-G needle in terms of diagnostic yield for cyto-histological evaluation of hilar and mediastinal lymphadenopathies. There is no difference between the 19-G and 22-G needle cell counts evaluated by flow cytometry.

Purpose The aim of the study was to assess the length of diagnostic delay of symptomatic endometriosis in Italy and analyse the presence of correlations between the socio-demographic status of patients and the clinical characteristics/type of diagnosis. Materials and methods This multicenter cross-sectional questionnaire-based study was conducted in 10 tertiary Italian referral centres for diagnosis and treatment endometriosis. A total of 689 respondents with histologically proven endometriosis and onset of the disease with pain symptoms completed an on-line self-reported questionnaire written in their own language (World Endometriosis Research Foundation-Endometriosis Phenome and Biobanking Harmonisation Project-Endometriosis Patient Questionnaire-Minimum) evaluating endometriosis related symptoms, family history of endometriosis and chronic pelvic pain, demographic data, as well as medical, reproductive, and obstetric history. Results The mean diagnostic delay found was of 11.4 years. The mean time (14.8 years) from symptoms onset to diagnosis was significantly longer among patients aged 9-19 vs patients aged 20-30 (mean 6.9 years, p < 0.001) and patients aged 31-45 (mean 2.9, p < 0.001). No significant association were found between a delayed diagnosis and any of the clinically relevant factors such as the number or severity of the reported symptoms, familiarity, hormonal therapy intake or methodology of diagnosis. Conclusions The mean diagnostic delay of endometriosis in Italy is about 11 years. The delay can be up to 4 years longer in patients with pain symptoms onset under 20 years. Educating clinicians and patients on pathologic nature of endometriosis related pelvic pain is advisable to reduce waiting time to diagnosis, especially for young women.

Background: The success of targeted therapies in the treatment of pancreatic neuroendocrine tumors has emphasized the strategy of targeting angiogenesis and the PI3K/AKT/mTOR pathway. However, the major challenge in the targeted era remains the early identification of resistant tumors especially when the efficacy is rarely associated to a clear tumor shrinkage at by imaging assessment. Methods: In this prospective study (NCT02305810) we investigated the predictive and prognostic role of soluble biomarkers of angiogenesis turnover (VEGF, bFGF, VEGFR2, TSP-1) circulating endothelial cells and progenitors, in 43 patients with metastatic panNET receiving everolimus. Results: Among all tested biomarkers, we found a specific subpopulation of circulating cells, CD31+CD140b-, with a significantly increased tumor progression hazard for values less or equal to the first quartile. Conclusion: Our study suggested the evidence that circulating cells might be surrogate biomarkers of angiogenesis activity in patients treated with everolimus and their baseline levels can be correlated with survival. However, further studies are now needed to validate the role of these cells as surrogate markers for the selection of patients to be candidates for antiangiogenic treatments.

Vascular infiltration may jeopardize resection of the primary tumor and mesenteric metastatic masses in small-intestine neuroendocrine tumors (SI-NETs). However, other factors may play a role in predicting resectability. After computed tomography (CT) scan, three radiological parameters were considered: (1) degree of superior mesenteric artery involvement (SMA) according to a previous classification (2) degree of superior mesenteric venous involvement (SMV) as either absent, peripheral or proximal (3) presence or not of mesenteric fibrosis retraction (MF). Pre-surgical parameters were matched to surgical outcome. Forty-nine consecutive patients were submitted to laparotomy. Of them, 37 had complete primary tumor and mesenteric masses resection. SMA (p = 0.001), SMV (p = 0.008), metastasis site (p = 0.001) and MF (p < 0.001) were all significantly associated with the likelihood to receive resection at univariate analysis. All the five patients with infiltration of SMV proximal to middle colic vein were unresectable. At multivariable analysis excluding SMA stage, the absence of MF (HR 13.1, I.C. 1.44–119; p = 0.002) was the only factor associated with the likelihood to receive primary tumor and mesentery radical surgery. SMA stage 3-up and/or signs of MF, as well as infiltration of SMV proximal to middle colic vein at CT scan are predictive of operative failure in patients with SI-NETs. The assessment of such factors should be always considered in the decision-making process of such patients especially in those with asymptomatic disease with synchronous unresectable liver metastases.

This study aims to analyze the sensitivity of vaginosonography (VGS) and magnetic resonance imaging (MRI) in the preoperative local evaluation of early-stage cervical cancers and to assess their accuracy in the detection of tumors, size of the lesions and stromal invasion by comparing them with the final histopathology report. This single-center study included 56 consecutive patients with cervical cancer who underwent VGS and MRI from November 2012 to January 2021. VGS significantly overestimated the lesion size by 2.7 mm (p = 0.002), and MRI underestimated it by 1.9 mm (p = 0.11). Both MRI and VGS had a good concordance with the pathology report (Cohen’s kappa of 0.73 and 0.81, respectively). However, MRI had a false-negative rate (38.1%) that was greater than VGS (0%) in cases of cervical tumor size <2 cm. We found a good concordance between histology and VGS in the stromal infiltration assessment, with 89% sensitivity (95% CI 0.44–0.83) and 89% specificity (95% CI 0.52–0.86). VGS is a simple, inexpensive, widely available, and fast execution method that can complement ultrasound in particular cases and show a good correlation with MRI in the assessment of tumor dimensions, with a better performance in detecting small tumors (<2 cm).

Background: The prevalence of reaches up to 5% in women younger than 40 years. Therefore, the fertility preservation should be the goal of the clinical practice in women with desire of pregnancy and low-risk features. The aim of this study is to compare oncological and reproductive outcomes of different hormonal therapies in FST of EC. Methods: A retrospective single-center study recruiting patients with presumed FIGO STAGE IA endometrioid G1 EC from 2005 to 2020 was performed. We assessed outcomes for three different therapeutic options: GnRHa + LNG-IUD vs. MA + LNG-IUD vs. MA + LNG-IUD + MET. Results: In total, 75 patients were enrolled and followed up for a median of 45 months. Complete response (CR) was achieved in 75% of patients at 12 months. Although not statistically significant, we reported an increasing rate of CR from the regimen with GnRHa to the one with MA + MET (65% vs. 83%). We showed a statistically significant lower risk of recurrence in women treated with MA + LNG-IUD + MET, when compared to GnRHa + LNG-IUD regimen. The pregnancy rate was 74% and live birth rate was 42%, with no differences among regimens. Conclusions: FST is a safe and effective option in women who desire to preserve fertility.

PurposeThis study aimed to assess if CT-derived body composition values and clinical characteristics are associated with the risk of postsurgical complications in men and women who underwent pneumonectomy for lung cancer. Materials and MethodsPatients who underwent pneumonectomy between 2004 and 2008 were selected. The ethics committee approved this retrospective study with waiver of informed content. Main clinical data collected were sex, age, weight and height to calculate body mass index (BMI), albumin, C-reactive protein, smoking status, side, sarcopenia, presurgical treatments, reoperation, and complications within 30 days after pneumonectomy, classified as: lung complications, cardiac complications, other complications, and any complication. From an axial CT image at the level of L3, automatic segmentations were performed to calculate skeletal muscle area (SMA), skeletal muscle density, subcutaneous adipose tissue, and visceral adipose tissue. Skeletal muscle index was calculated as SMA/square height. Univariate and multivariate logistic regression analyses were performed to estimate the risk of any complication, both on the total population and in a by sex subgroup analysis. All tests were two tailed and considered significant at 5% level. ResultsA total of 107 patients (84 men and 23 women) were included. Despite no significant differences in BMI, there were significant differences of body composition values in muscle and adipose tissue parameters between men and women, with women being significantly more sarcopenic than men (p = 0.002). Separate analyses for men and women showed that age and SMA were significantly associated with postoperative complications in men (p = 0.03 and 0.02, respectively). ConclusionsBody composition measurements extracted from routine CT may help in predicting complications after pneumonectomy, with men and women being different in quantity and distribution of muscle and fat, and men significantly more prone to postpneumonectomy complications with the increase of age and the decrease of skeletal muscle area.

BACKGROUND:HPV tests differ for technology, targets, and information on genotyping of high risk (HR) HPV. In this study, we evaluated the performance of 6 HPV DNA tests and one mRNA test in the detection of cervical intraepithelial lesions (CIN) and as a test-of-cure in the follow-up after surgical conservative treatment.METHODS:One hundred seventy-two women referred to the European Institute of Oncology, Milan, for surgical treatment of pre-neoplastic cervical lesions, were enrolled in this study (IEO S544) from January 2011 to June 2015. For all women, a cervical sample was taken before treatment (baseline) and at the first follow-up visit (range 3 to 9 months): on these samples Qiagen Hybrid Capture 2 (HC2), Roche Linear Array HPV Test (Linear Array), Roche Cobas 4800 HPV test (Cobas), Abbott RealTime High Risk HPV test (RT), BD Onclarity HPV assay (Onclarity), Seegene Anyplex II HPV HR Detection (Anyplex), and Hologic Aptima HPV Assay (Aptima) histology and cytology were performed at baseline, and the same tests and cytology were performed at follow-up.RESULTS:At baseline 158/172 (92%), histologies were CIN2+, and 150/172 (87%) women were recruited at follow-up. Assuming HC2 as a comparator, the concordance of HPV tests ranges from 91% to 95% at baseline and from 76% to 100% at follow-up (PABAK ranging from 0.81 to 0.90 at baseline and PABAK ranging from 0.53 to 1 at follow-up). All HPV showed a very good sensitivity in CIN2+ detection at baseline, more than 92%, and a very good specificity at follow-up, more than 89%.CONCLUSIONS:HPV tests showed a good concordance with HC2 and a very good and comparable sensitivity in CIN2+ detection. Hence, an HPV test represents a valid option as test-of-cure in order to monitor patients treated for CIN2+ lesions during follow-up.

Background: Many data are available on pneumonectomy for cancer in adults and for non-oncologic diseases in patients younger than 10 years, whereas few reports have addressed pneumonectomy for cancer in adult patients younger than 30 years. Given the increased number of younger patients diagnosed nowadays with pulmonary neoplasms and the need of salvage surgery after modern inductions or definitive treatments, it is worth to know the impact of salvage pneumonectomy in patients younger than 30 years. Methods: From 1998 to 2018, 943 pneumonectomies for cancer were performed at our department, including 14 in adult patients younger than 30 years. All patients but two had previously undergone medical, radiotherapic or surgical treatments without any effective clinical impact. Age, gender, smoking habits, type, side and extent of surgical resection, oncologic history, pathological findings, post-operative course, 30-day or in-hospital morbidity and mortality rates and long-term follow-up were retrospectively collected. Results: Eight patients were female; median age was 26 years. Two out of 14 patients had primary non-small cell lung cancers, 1/14 pulmonary atypical carcinoid, 6/14 pulmonary metastases, 2/14 synovial sarcoma, 1/14 Hodgkin lymphoma, 1/14 thymoma and 1/14 desmoid tumor. 6/14 patients had postoperative complications: 3/6 had hemothorax requiring re-do surgical exploration; 1/6 had early bronchopleural fistula; 1/6 had monolateral vocal cord palsy; 2/6 patient developed acute respiratory distress syndrome and subsequently died on 17th postoperative day. Conclusions: Postoperative morbidity is not negligible and salvage pneumonectomy for cancer in patients younger than 30 years should therefore be considered only in case all the available therapeutic options have failed.

Background: An unplanned return to the operating room (UROR) is defined as a readmission to the operating room because of a complication or an untoward outcome related to the initial surgery. The aim of the present report is to evaluate the role of URORs after elective oncologic thoracic surgery. Methods: In the study, 4012 consecutive patients were enrolled; among them, 71 patients (1.76%) had an unplanned return to the operating room. Age, sex, Charlson comorbidity index, induction treatments, type of the first operation, indication to readmission to the operating room and type of second operation, length of stay, complication after reoperation and outcomes were collected. Results: The mean age was 63.3 (SD: 13.0); there were 53 male patients (74.6%); the type of the first procedure was: lower lobectomy (11.3%), middle lobectomy (1.4%), upper lobectomy (22.5%), metastasectomy (5.6%), extrapleural pneumonectomy (4.2%), pneumonectomy (40.9%), pleural biopsy (5.6%) and other procedures (8.5%). Patients presenting complications after UROR had undergone a significantly longer first procedure (p < 0.02), had a longer length of stay (p < 0.001) and had higher post-operative mortality (p < 0.001). Conclusions: The patients experiencing UROR after elective oncologic thoracic surgery have significantly higher morbidity and mortality rates when compared to standard thoracic surgery. Bronchopleural fistula remains the most lethal complication in patients undergoing UROR.

Background and objectives: The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated that in clinically node-negative women undergoing breast-conserving therapy (BCT) and found to have metastases to 1 or 2 sentinel nodes, sentinel lymph node biopsy (SLNB) alone resulted in rates of local control, disease-free survival, and overall survival equivalent to those seen after axillary lymph node dissection (ALND), but with significantly lower morbidity. Application of the Z0011 guidelines resulted in fewer ALNDs without affecting locoregional recurrence or survival. Changes in practice inevitably affect health care costs. The current study investigated the actual impact of applying the Z0011 guidelines to eligible patients and determined the costs of care at a single institution. Patients and methods: We compared axillary nodal management and cost data in breast cancer patients who met the Z0011 criteria and were treated with BCT and SLNB. Patients were allocated into two mutually exclusive cohorts based on the date of surgery: pre-Z0011 (June 2013 to December 2015) and post-Z0011 (June 2016 to December 2018). Results: Of 3912 patients, 433 (23%) and 357 (17.6%) patients in the pre-and post-Z0011 era had positive lymph nodes. ALND decreased from 15.3% to 1.57% in the post-Z0011 era. The mean overall cost of SLNB in the pre-Z0011 cohort was euro1312 per patient, while that for SLNB with completion ALND was euro2613. Intraoperative frozen section (FS) use decreased from 100% to 12%. Omitting the FS decreased mean costs from euro247 to euro176. The mean total cost in the pre-Z0011 cohort was euro1807 per patient, while in the post-Z0011 cohort it was euro1498. The application of Z0011 resulted in an overall mean cost savings of euro309 for each patient. Conclusions: Application of the Z0011 criteria to patients undergoing BCT at our institution results in more than half a million Euro cost savings. (c) 2021 Published by Elsevier Ltd.