Reproductive Outcomes in Young Women with Early-Stage Cervical Cancer Greater than 2 cm Undergoing Fertility-Sparing Treatment: A Systematic Review.

Background and Objectives: Despite advancements in detection and treatment, cervical cancer remains a significant health concern, particularly among young women of reproductive age. Limited data exists in the literature regarding fertility-sparing treatment (FST) of cervical cancers with tumor sizes greater than 2 cm. The objective of this systematic review was to evaluate the reproductive outcomes of women diagnosed with cervical cancer greater than 2 cm who underwent FST. Materials and Methods: A comprehensive search of the literature was carried out on the following databases: MEDLINE, EMBASE, Global Health, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), the Health Technology Assessment Database, and Web of Science. Only original studies (retrospective or prospective) that reported reproductive outcomes of patients with cervical cancer >2 cm were considered eligible for inclusion in this systematic review (CRD42024521964). Studies describing only the oncologic outcomes, involving FST for cervical cancers less than 2 cm in size, and case reports were excluded. Results: Seventeen papers that met the abovementioned inclusion criteria were included in the present systematic review. In total, 443 patients with a cervical cancer larger than 2 cm were included in this systematic review. Eighty pregnancies occurred, with 24 miscarriages and 54 live births. Conclusions: FST appears to be a viable option for women of childbearing age diagnosed with cervical cancer larger than 2 cm. However, careful consideration is advised in interpreting these encouraging results, as they are subject to limitations, such as variability in study designs and potential biases. In addition, reproductive outcomes should be further cross-referenced with oncologic outcomes to clarify the potential risk-benefit ratio. It is critical to conduct further research using standardized approaches and larger participant groups to strengthen the validity of the conclusions drawn.

Population characteristics, management, and survival outcomes in muscle-invasive urothelial carcinoma undergoing radical resection: the MINOTAUR study.

PURPOSE: To describe the incidence, management, and survival outcomes of patients with muscle-invasive urothelial carcinoma (MIUC) undergoing radical surgery (RS) in France. METHODS: We relied on a non-interventional real-world retrospective study based on French National Hospitalization Database. Adults with MIUC with a first RS between 2015 and 2020 were selected. Subpopulations of patients with RS performed in 2015 and 2019 (pre-COVID-19) were extracted, according to cancer site: muscle-invasive bladder cancer (MIBC) or upper tract urothelial carcinoma (UTUC). Disease-free and overall survival (DFS, OS - Kaplan-Meier) were assessed on the 2015 subpopulation. RESULTS: Between 2015 and 2020, 21,295 MIUC patients underwent a first RS. Of them, 68.9% had MIBC, 28.9% UTUC, and 2.2% both cancers. Apart from fewer men among UTUC (70.2%) than MIBC patients (90.1%), patients' demographic (mean age ~ 73 years) and clinical characteristics were similar whatever the cancer site or year of first RS. In 2019, RS alone was the most frequent treatment, occurring in 72.3% and 92.6% in MIBC and UTUC, respectively. Between 2015 and 2019, neoadjuvant use rate increased from 13.8% to 22.2% in MIBC, and adjuvant use rate increased from 3.7% to 6.3% in UTUC. Finally, median [95% confidence interval] DFS times were 16.0 [14.0-18.0] and 27.0 [23.0-32.0] months among MIBC and UTUC, respectively. CONCLUSION: Among patients with resected MIUC annually, RS alone remained the main treatment. Neoadjuvant and adjuvant use increased between 2015 and 2019. Nonetheless, MIUC remains of poor prognosis, highlighting an unmet medical need, notably among patients at high risk of recurrence.

Cancer embryonic antigen (CEA) levels in patients with appendiceal adenocarcinoma predict response to neo-adjuvant chemotherapy and overall survival.

BACKGROUND AND OBJECTIVES: Serum tumor markers are widely used for diagnosis, prognosis, treatment response, and surveillance. Our study evaluated cancer embryonic antigen (CEA) in patients with appendiceal adenocarcinoma. METHODS: The National Cancer Database was reviewed (2004-2011) for patients with surgical treatment for appendiceal adenocarcinoma. Patients were stratified into two groups: normal and elevated CEA. Multivariable adjusted Cox proportional hazards regression analyses were used to determine the independent effect of CEA on survival. RESULTS: Our study consisted of 2867 patients, 54.0% having elevated CEA. Patients with elevated CEA were more likely to have Stage IV disease, be female, and African American; all p < 0.001. Three-year overall survival (OS) was significantly higher with normal CEA (75.5% vs. 62.8%, p < 0.001). On multivariable analysis, elevated CEA was associated with worse survival (hazard ratio 1.49, 95% confidence interval 1.23-1.80). Patients with elevated CEA had improved 3-year OS with neo-adjuvant compared to adjuvant chemotherapy (p = 0.004), while those with normal CEA showed no difference. CONCLUSIONS: In patients with surgically treated appendiceal adenocarcinoma, preoperative elevation in CEA independently predicts decreased 3-year survival and correlates with improved OS with neo-adjuvant therapy. CEA levels should be considered in clinical decision-making regarding neo-adjuvant therapy in patients with appendiceal adenocarcinoma.

Is complete pathological response truly a complete response in breast cancer?

OBJECTIVE: To check if complete pathological response in breast cancer is a good prognostic factor. METHODS: The retrospective study was conducted at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised data from January 2012 to December 2015 of all patients who received neo-adjuvant chemotherapy and had no distant metastasis at diagnosis. Mastectomy patients were excluded. Complete pathological response was defined as no detectable tumour cell in breast and axilla on pathological examination of the resected specimen. Tumour characteristics and 5-year disease free survival and overall survival were recorded. Data was analysed using SPSS 20. RESULTS: Of the 353 patients whose data was evaluated, 91(25.8%) had complete pathological response. Mean age at diagnosis was 43±10 years. Among them, 62(68%) patients had grade III tumour, 39(42.9%) were negative for oestrogen receptor, 58(63.7%) were negative for progesterone receptor, 25(27.5%) were positive for human epidermal growth factor receptor 2, and 26(28.6%) patients were triple negative. Overall, 28((30.7%) patients had recurrence; 20(71.4%) had distant metastasis, 6(21.4%) had local recurrence, and 2(7.14%) had contralateral cancer. The 5-year disease-free survival and overall survival rates (Kaplan-Meier Survial curve) were 70% (28 patients-recurrence) and 87% (15 patients-deaths), respectively. Conclusion: Despite complete disappearance of tumour, a significant number of patients developed recurrences.

Sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with node-positive breast cancer: guiding a more selective axillary approach.

PURPOSE: The role of sentinel lymph node biopsy (SLNB) in breast cancer patients who undergo neoadjuvant chemotherapy (NAC) remains controversial. This study aims to investigate if axillary lymph node dissection (ALND) could be safely omitted after a negative SLNB in cN1/2 patients who become cN0 after NAC. METHODS: We retrospectively assessed T1-4, cN1/2 patients who were submitted to NAC between 2010 and 2016. T1-T3 patients who achieved complete axillary clinical response underwent SLNB. Those whose SLNs were negative were not subjected to additional ALND. The oncological outcomes of the patients were analyzed. RESULTS: Fifty-nine T1-T3 patients (45.0%) achieved a complete axillary response (cN0), and were selected to undergo SLNB. SLNs were detected in 55 of them (93.2%). Seventeen of those patients (30.9%) had SLN metastases detected and subsequently underwent ALND. In contrast, 38 patients (69.1%) had no nodal metastases detected and were managed without complementary ALND. After a mean follow-up of 55.8 months, only one patient (2.6%) submitted to SLNB without a complementary ALND had axillary recurrence as compared with three patients (3.2%) in the ALND group (p = 0.71). Distant recurrence occurred more frequently among patients submitted to ALND (92.1%) than among those only submitted to SLNB (7.9%) (p < 0.0006). Overall survival and disease-free survival were significantly better in patients who were not submitted to ALND. CONCLUSION: SLNB could be successfully used in guiding a more selective axillary approach in cN+ patients that became cN0 after NAC. Omitting ALND in CN0 patients with negative SLNs did not seem to compromise disease control and oncological outcomes.

The role of capecitabine-based neoadjuvant and adjuvant chemotherapy in early-stage triple-negative breast cancer: a systematic review and meta-analysis.

BACKGROUND: The role of capecitabine in neoadjuvant and adjuvant chemotherapy for early-stage triple-negative breast cancer (TNBC) is highly controversial. Our meta-analysis was designed to further elucidate the effects of capecitabine on survival in early-stage TNBC patients and its safety. METHODS: PubMed, Embase, and papers presented at several main conferences were searched up to December 19, 2019, to investigate capecitabine-based versus capecitabine-free neoadjuvant and adjuvant chemotherapy in TNBC patients. Heterogeneity was assessed using I2 test, combined with hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI) computed for disease-free survival (DFS), overall survival (OS), and over grade 3 adverse events (AEs). RESULTS: A total of 9 randomized clinical trials and 3842 TNBC patients were included. Overall, the combined capecitabine regimens in neoadjuvant and adjuvant chemotherapy showed significantly improved DFS (HR = 0.75; 95% CI, 0.65-0.86; P < 0.001) and OS (HR = 0.63; 95% CI, 0.53-0.77; P < 0.001). In subgroup analysis, there were improvements in DFS in the groups with addition of capecitabine (HR = 0.64; 95% CI, 0.53-0.78; P < 0.001), adjuvant chemotherapy (HR = 0.73; 95% CI, 0.63-0.85; P < 0.001), and lymph node positivity (HR = 0.62; 95% CI, 0.44-0.86; P = 0.005). Capecitabine regimens were related to higher risks of diarrhea (OR = 2.88, 95% CI 2.23-3.74, P < 0.001), stomatitis (OR = 2.01, 95% CI 1.53-2.64, P < 0.001) and hand-foot syndrome (OR = 8.67, 95% CI 6.70-11.22, P < 0.001). CONCLUSION: This meta-analysis showed that neoadjuvant and adjuvant chemotherapy combined with capecitabine significantly improved both DFS and OS in early-stage TNBC patients with tolerable AEs. There were benefits to DFS in the groups with the addition of capecitabine, adjuvant chemotherapy, and lymph node positivity.

Neo-CheckRay: radiation therapy and adenosine pathway blockade to increase benefit of immuno-chemotherapy in early stage luminal B breast cancer, a randomized phase II trial.

BACKGROUND: Residual breast cancer after neo-adjuvant chemotherapy (NACT) predicts disease outcome and is a surrogate for survival in aggressive breast cancer (BC) subtypes. Pathological complete response (pCR) rate, however, is lower for luminal B BC in comparison to the triple negative (TNBC) and HER2+ subtypes. The addition of immune checkpoint blockade (ICB) to NACT has the potential to increase pCR rate but is hampered by the lower immunogenicity of luminal B BC. Novel strategies are needed to stimulate the immune response and increase the response rate to ICB in luminal B BC. METHODS: The Neo-CheckRay trial is a randomized phase II trial investigating the impact of stereotactic body radiation therapy (SBRT) to the primary breast tumor in combination with an anti-CD73 (oleclumab) to increase response to anti PD-L1 (durvalumab) and NACT. The trial is designed as a three-arm study: NACT + SBRT +/- durvalumab +/- oleclumab. The result at surgery will be evaluated using the residual cancer burden (RCB) index as the primary endpoint. Six patients will be included in a safety run-in, followed by a randomized phase II trial that will include 136 evaluable patients in 3 arms. Inclusion is limited to luminal B breast cancers that are MammaPrint genomic high risk. DISCUSSION: combination of ICB with chemotherapy in luminal B BC might benefit from immune priming agents to increase the response rate. As none have been identified so far, this phase II trial will evaluate SBRT and oleclumab as potential immune priming candidates. TRIAL REGISTRATION: trial registered on ClinicalTrials.gov ( NCT03875573 ) on March 14th, 2019.

Evaluating the impact of 18F-FDG-PET-CT on risk stratification and treatment adaptation for patients with muscle-invasive bladder cancer (EFFORT-MIBC): a phase II prospective trial.

BACKGROUND: The outcome of patients with muscle-invasive bladder cancer (MIBC) remains poor, despite aggressive treatments. Inadequate primary staging, classically performed by computed tomography (CT)-imaging, could lead to inappropriate treatment and might contribute to these poor results. Although not (yet) adapted by international guidelines, several reports have indicated the superiority of 18F-fluorodeoxyglucose-positron emission tomography-CT (18F-FDG-PET-CT) compared to CT in the detection of lymph node and distant metastases. Thereby the presence of extra-vesical disease on 18F-FDG-PET-CT has been correlated with a worse overall survival. This supports the hypothesis that 18F-FDG-PET-CT is useful in stratifying MIBC patients and that adapting the treatment plan accordingly might result in improved outcome. METHODS: EFFORT-MIBC is a multicentric prospective phase II trial aiming to include 156 patients. Eligible patients are patients with histopathology-proven MIBC or ≥ T3 on conventional imaging treated with MIBC radical treatment, without extra-pelvic metastases on conventional imaging (thoracic CT and abdominopelvic CT/ magnetic resonance imaging (MRI)). All patients will undergo radical local therapy and if eligible neo-adjuvant chemotherapy. An 18F-FDG-PET-CT will be performed in addition to and at the timing of the conventional imaging. In case of presence of extra-pelvic metastasis on 18F-FDG-PET-CT, appropriate intensification of treatment with metastasis-directed therapy (MDT) (in case of ≤3 metastases) or systemic immunotherapy (> 3 metastases) will be provided. The primary outcome is the 2-year overall survival rate. Secondary endpoints are progression-free survival, distant metastasis-free survival, disease-specific survival and quality of life. Furthermore, the added diagnostic value of 18F-FDG-PET-CT compared to conventional imaging will be evaluated and biomarkers in tumor specimen, urine and blood will be correlated with primary and secondary endpoints. DISCUSSION: This is a prospective phase II trial evaluating the impact of 18F-FDG-PET-CT in stratifying patients with primary MIBC and tailoring the treatment accordingly. We hypothesize that the information on the pelvic nodes can be used to guide local treatment and that the presence of extra-pelvic metastases enables MDT or necessitates the early initiation of immunotherapy leading to an improved outcome. TRIAL REGISTRATION: The Ethics Committee of the Ghent University Hospital (BC-07456) approved this study on 11/5/2020. The trial was registered on ClinicalTrials.gov (NCT04724928) on 21/1/2021.

Incidental radiologic findings in breast cancer patients who undergo staging prior to neo-adjuvant chemotherapy.

NCCN guidelines discourage the use of staging imaging for newly diagnosed patients with early breast cancer (BC). When performed, incidental radiologic findings of uncertain significance are often encountered. The purpose of this study was to compare incidental findings seen on staging imaging with distant recurrence in patients undergoing neo-adjuvant chemotherapy (NAC). 396 patients with BC who had NAC from 2008 to 2016 were identified from a prospectively maintained data base. Staging imaging was reviewed. Of 396 patients with BC treated with NAC, patients with a positive PET/CT for metastatic disease (n = 36, 9.1%), those that did not undergo staging imaging (n = 49, 12.4%), or those that did not have a reported incidental finding (n = 49, 12.4%) were excluded from analysis. Of the 262 patients who met criteria, mean age was 50 years (range: 26-88). 201 (76.7%) patients had stage I-II cancer, and 61 (23.3%) patients had stage III cancer. Overall, 146 (55.7%) patients had an incidental finding on imaging. 90 (34.4%) patients had one finding, 42 (16.0%) patients had two, and 14 (5.3%) patients had three or more findings. The majority of incidental findings were seen in the ovary/uterus (29.7%), followed by lung (18.4%), liver (10.3%), and bone (9.0%). 5 (3.4%) patients had additional imaging performed. At mean follow-up of 3.7 years (range: 0.7-10.8), 43 (15.6%) patients had a distant recurrence. Of these patients, only 5 (1.9%) patients had distant metastasis in the same organ that was initially thought to be an incidental finding. Our results suggest that breast cancer patients with incidental findings on preoperative staging imaging are unlikely to be indicative of sites for future metastasis.

Does the false-negative rate for 1 or 2 negative sentinel nodes after neo-adjuvant chemotherapy translate into a high local recurrence rate?

Prospective trials demonstrate that sentinel node (SN) biopsy after neo-adjuvant chemotherapy (NACT) has a significant false-negative rate (FNR) when only 1 or 2 SNs are removed. It is unknown whether this increased FNR correlates with an elevated risk of recurrence. Tumor Registry data at an NCI-Designated Comprehensive Cancer Center were reviewed from 2004 to 2018 for patients having a negative SN biopsy after NACT. Among 190 patients with histologically negative nodes after NACT having 1 (n = 42), 2 (n = 46), and ≥3 (n = 102) SNs, axillary recurrences occurred in 7.14%, 0%, and 1.96% (p = 0.09), breast recurrences occurred in 2.38%, 6.52%, and 0.98% (p = 0.12), and distance recurrences occurred in 16.67%, 8.70%, and 7.84% (p = 0.27), respectively. Time to first recurrence did not differ by SN count (p = 0.41). After adjustment for age, race, clinical stage, and receptor status, there were no differences in the rates of axillary (p = 0.26), breast (p = 0.44), or distance recurrence (p = 0.24) by numbers of SNs harvested. Median follow-up was 46.8 months. Despite higher post-NACT FNRs reported in randomized trials for patients having <3 sentinel nodes, recurrence rates were not significantly different for 1 versus 2 versus ≥3 SNs. This suggests that patients having 1 or 2 post-NACT SNs identified may not necessitate axillary dissection.

Covered self-expandable metal stents versus plastic stents for preoperative biliary drainage in patient receiving neo-adjuvant chemotherapy for borderline resectable pancreatic cancer: Prospective randomized study.

OBJECTIVES: This single-center comparative randomized superiority study compared biliary stenting using fully covered self-expandable metal stents (FCSEMS) and biliary stenting using plastic stents (PS) in preoperative biliary drainage of patients with borderline resectable pancreatic cancer (BRPC) who are planned to undergo a single regimen of neo-adjuvant chemotherapy (NAC). METHODS: Twenty-two patients with BRPC who required preoperative biliary drainage before NAC (Gemcitabine plus Nab-paclitaxel) were randomly assigned 1:1 to the FCSEMS or PS group. The primary endpoint was the rate of stent dysfunction until surgery or tumor progression. Secondary endpoints were stent patency, number of re-interventions, adverse events of endoscopic retrograde biliary drainage (EBD), operation time, volume of intraoperative bleeding, postoperative hospitalization, postoperative adverse events and medical costs. RESULTS: Eleven patients in each of the groups reached the primary endpoint. The FCSEMS group showed a significantly lower rate of stent dysfunction (18.2% vs. 72.8%, P = 0.015), longer stent patency (P = 0.02), and lower number of re-interventions for stent dysfunction (0.27 ± 0.65 vs. 1.27 ± 1.1, P = 0.001) than the PS group. The adverse events of EBD, operation time, volume of intraoperative bleeding, postoperative hospitalization, postoperative adverse events and medical costs did not significantly differ between the two groups. CONCLUSIONS: In patients with BRPC for preoperative biliary drainage, stent dysfunction occurred less frequently with FCSEMSs than with PSs. In addition, FCSEMS and PS provided similar preoperative management of BRPC in terms of the safety of surgery and medical costs. (UMIN ID000030473).

Current status of perioperative chemotherapy for locally advanced gastric cancer and JCOG perspectives.

Perioperative treatment for locally advanced gastric cancer has been inconsistent between Japan and the Western countries. In Japan, D2 gastrectomy followed by adjuvant chemotherapy is regarded as standard treatment, while neoadjuvant or perioperative chemotherapy is considered to be a standard in the Western countries. Stomach Cancer Study Group of Japan Clinical Oncology Group (JCOG) has conducted many perioperative chemotherapy trials. After the publishing of positive results of ACTS-GC trial, stage-specific adjuvant chemotherapy protocols are planned. JCOG1104 was conducted as to demonstrate the non-inferiority of four courses of S-1 to standard eight courses of S-1, because the efficacy of S-1 appears to be sufficient in stage II. The trial failed to demonstrate the non-inferiority of four courses of S-1. S-1 for 1 year is still recognized to be a standard for stage II gastric cancer. For stage III, studies with more intensive treatments were planned as the efficacy of S-1 monotherapy seems to be insufficient. As in the Western countries, JCOG planned the perioperative chemotherapy. However, the clinical staging is a serious issue to select optimal patients for perioperative chemotherapy. JCOG conducted a prospective cohort study to evaluate the validity of clinical staging in JCOG1302A. From the results of this study, cT3-4 and cN1-3 are selected as optimal candidate for perioperative chemotherapy. JCOG1509 was conducted to demonstrate the superiority of perioperative chemotherapy to adjuvant chemotherapy in these cohorts. Perioperative chemotherapy for marginally resectable tumours such as linitis plastica or extensive nodal disease and special type of cancer like HER2 positive are also conducted.

No Difference in Survival between Neo-Adjuvant Chemotherapy and Neo-Adjuvant Chemoradiation Therapy in Gastric Cardia Cancer Patients: A Contemporary View from the National Cancer Database.

INTRODUCTION: Both neo-adjuvant chemoradiation therapy (NACRT) and neo-adjuvant chemotherapy (NAC), in addition to surgical resection of gastric cardia cancer, improves survival outcomes. We assessed whether NACRT or NAC had superior overall survival (OS) and relative survival (RS) outcomes using the National Cancer Database (NCDB). METHODS: The NCDB from 2006 to 2014 was reviewed to identify non-metastatic adult gastric cardia cancer patients who underwent surgical resection and received NACRT or NAC. Advanced statistical models were applied to assess survival outcomes. RESULTS: Of the 5,371 patients included, 4,520 (84.2%) were male, the mean age was 61.2 years (SD 10.0), 4,229 (78.7%) underwent NACRT, and 1,142 (21.3%) underwent NAC. NACRT patients more often had an R0 resection compared to NAC (91.4 vs. 86.6%, p < 0.001, respectively). Univariate 5-year OS rates were 40.0% (95% CI 38.2-41.8) for NACRT and 40.1% (37.0-43.6) for NAC (p = 0.302). No differences in OS for NAC vs. NACRT were found after multivariable analysis (hazard ratio [HR] 0.95, 95% CI 0.86-1.05, p = 0.290). There were no survival differences after stepwise, propensity score, RS analyses, nor after near-far-matching (HR 0.94, 95% CI 0.82-1.07, p = 0.332). CONCLUSIONS: NAC or NACRT yield the same survival outcome for patients with resectable gastric cardia cancer. These data support the need for randomized controlled trials comparing the 2 regimens head-to-head.

Neo-adjuvant chemotherapy alone for the locally advanced rectal cancer: a systematic review.

Neo-adjuvant chemoradiation (NA-CRT) is the standard of management for the locally advanced rectal cancer (LARC), achieving very low rates of local recurrence (LR). However, NA-CRT fails to control distant recurrence and improve survival, whilst it is associated with increased postoperative morbidity and increased acute and late toxicity. In recent years, neo-adjuvant chemotherapy (NACTx) appears in the literature as an alternative to NA-CRT in patients with LARC. In the present study, the authors review all current evidence on the specific subject. Following a systematic search of the literature, 25 studies were identified reporting on short- or long-term outcomes of NACTx for LARC. Seventeen studies were prospective or retrospective series, and 8 comparative. Of the comparative studies, one was a randomized control trial (RCT) comparing NACTx to NA-CRT and to the combination of NACTx/NA-CRT, and another a non-randomized study comparing NACTx to NA-CRT. Chemotherapeutic regimens were 5-fluoropyrimidine and oxaliplatin based. In some of them, irinotecan or/and bevacizumab was added. A pooled analysis showed that NACTx is associated with a mean anastomotic leak rate of 6.8%. In the RCT, postoperative morbidity and overall toxicity was significantly less in the NACTx group. Mean T downstaging (ypStage 0-I) was 49.6%, mean N downstaging 69.6% and mean pathologic complete response (pCR) 10.7%. The RCT showed an inferior pCR rate after NACTx than after NA-CRT, but similar rates of T downstaging. Mean LR was 8.6% and mean distant recurrence 17.2%. Satisfactory survival rates are reported by several studies. NACTx seems to be an alternative to NA-CRT for patients with LARC, associated with low anastomotic leak, adequate tumour downstaging, low LR and rather high survival rates. Further data deriving from high-quality studies are necessary to assess safety and efficacy of NACTx as a substitute to NA-CRT, for at least a subset of patients with LARC.

Does use of axillary ultrasound in clinically node-negative patients receiving neo-adjuvant systemic therapy for breast cancer lead to surgical overtreatment?

Increased use of neo-adjuvant chemotherapy (NAC) for breast cancer has raised uncertainty regarding staging of the axilla, particularly for patients with a clinically negative axillary physical examination (PE). We sought to determine whether axillary ultrasound (AUS) prior to NAC to identify occult nodal disease is beneficial in patients with a clinically negative examination by evaluating the difference in nodal burden on final pathology in those with abnormal vs normal AUS. A retrospective review of an institutional cancer registry identified patients who underwent NAC for breast cancer and had a pretreatment AUS. Differences in the number of positive lymph nodes (PLN) in patients with a normal axillary PE and abnormal vs normal AUS prior to NAC were determined. A total of 120 patients who received NAC had a negative axillary PE prior to treatment. Fifty-three had an abnormal AUS and biopsy-proven lymph node (LN) involvement. In patients with an abnormal AUS, median number of PLNs at surgery was 1 vs 0 for those with a normal AUS (mean difference of 2.12, P < .0001). Of those patients with an abnormal AUS and biopsy-proven LN involvement, 87% underwent axillary lymph node dissection (ALND) and nearly half had no PLN on final pathology (N = 23, 43%). Patients with a clinically negative axilla and an abnormal AUS were more likely to have PLN at the time of surgery. However, almost half of those patients had no residual LN involvement. Routine AUS prior to NAC may lead to more extensive surgical management of the axilla.

Management of the clinically positive axilla.

Axillary dissection has been the standard of care for any patient with clinically positive lymph nodes at initial breast cancer presentation. However, modern neo-adjuvant therapies can convert positive nodes to negative nodes, especially in the setting of HER2-positive disease. Accurate axillary staging can be achieved after neo-adjuvant therapy in initially node-positive patients using dual tracer lymphatic mapping, removal of three or more lymph nodes, and confirmation of excision of the previously biopsied and clipped lymph node. Currently accruing clinical trials are designed to determine which patients can safely avoid axillary dissection and/or axillary radiation.

Twenty-five years of change in the management of the axilla in breast cancer.

Sentinel lymph node (SLN) biopsy is now used worldwide. It has led to many changes in how we manage the axilla in patients with breast cancer. This review covers four areas of management of the axilla in breast cancer: assessing the clinically node-negative axilla, managing the clinically negative axilla found to be involved at SLN biopsy, management of the clinically positive axilla in the context of neo-adjuvant chemotherapy, and treatment of the diseased axilla when radical therapy is required. We suggest that the evidence supports an optimum number of 3 nodes to be removed for accurate SLN biopsy. Breast cancer departments that have not adopted Z0011 patient management cannot continue to avoid change. The evidence is clear: Not all patients with limited axillary nodal disease on sentinel node biopsy need axillary lymph node dissection. For patients who do need axillary treatment, axillary radiotherapy continues to be under-used. Patients undergoing neo-adjuvant chemotherapy can be safely assessed by post-therapy SLN biopsy, with retrieval of any previously biopsied involved nodes by targeted axillary dissection. There is much to support the trend to doing less in the axilla. We are obliged to act based on the available robust clinical trial data in a way that limits morbidity while at the same time does not increase the risk of disease recurrence.

Neo-Adjuvant chemotherapy and its affects to the axilla-Can we safely downgrade axillary surgery to mirror the approach in the breast.

The use of neo-adjuvant chemotherapy (NACT) to downgrade surgery in the breast from mastectomy to breast-conserving surgery is well-established. In certain patients, the use of adjuvant axillary radiotherapy can be safe and effective in place of axillary node clearance. What remains less clear are the alternative surgical options to the axilla following NACT. The aim of this study was to examine the effects of NACT in the axilla and whether downgrading axillary node clearance to axillary conserving surgery to mirror the approach in the breast may be a viable and safe practice. Patients undergoing neo-adjuvant chemotherapy were identified over a seven-year period between 2010 and 2017. Surgical plans were compared with pre- and post-chemotherapy. Histological information at the time of diagnosis was compared to surgical excision specimens. 349 patients were included for analysis, and 264 had axillary status documented at diagnosis. The average patient age was 51 years, and Grade 3, ER-positive, and Her2-negative cancers made the biggest histological subgroups. Complete pathological response (CPR) was seen in the breast in 27% of cases. 19% of patients requiring mastectomy had their surgery downgraded. Following NACT, axillary CPR was seen in 42% of patients and residual axillary nodal burden was limited to four nodes in 73% of patients. Axillary conserving surgery may be a safe alternative surgical approach in the downstaged axilla following neo-adjuvant chemotherapy. Advances in perioperative identification of suspicious nodes may be needed to facilitate progress.

Predictive factors for omitting lymphadenectomy in patients with node-positive breast cancer treated with neo-adjuvant systemic therapy.

A pathologic complete response (pCR) in the axilla occurs in 30%-40% of patients with initially node-positive breast cancer after neo-adjuvant chemotherapy (NACT). Debate persists about whether to perform systematic axillary lymphadenectomy (ALND) in patients with initial node-positive disease and clinical complete response after NACT. We aimed to identify predictive factors of axillary pCR (ypN0) after NACT. This retrospective study analyzed data for all patients with initial biopsy-proven node-positive disease who underwent ALND after NACT between June 2008 and December 2016 at our institution. Clinical and pathologic features, recurrence and specific mortality rates were compared between patients who achieved an axillary pCR and those who did not (ypN0 vs ypN+, respectively). A total of 331 patients were included, of whom 128 (38.7%) became ypN0 after NACT. Among patients with >2 suspicious axillary lymph nodes before treatment, 54 (38%) achieved ypN0 status. The independent predictors of ypN0 were Ki-67 > 30 (OR 1.98; 95% CI, 1.146-3.381), HER2 positivity (OR 2.6; 95% CI, 1.354-5.108), nonluminal molecular-like subtype (OR 4.15; 95% CI, 2.068-5.108), and clinical complete response, defined as negative clinical and ultrasonographic findings (OR 2.8; 95% CI, 1.110-7.081). After a mean follow-up of 61 months, distant disease-free and overall survival rates were higher in patients with ypN0 disease (HR 4.14; 95% CI, 2.03-8.43) than ypN+ patients. Complete clinical response and the presence of nonluminal molecular-like subtypes independently predicted ypN0. Patients meeting these criteria might be suitable form omitting ALND and just performing targeted axillary procedures to patients meeting these criteria.

Intraoperative ultrasonography-guided surgery: An effective modality for breast conservation after neo-adjuvant chemotherapy.

Margin status is one of the significant prognostic factors for recurrence in breast-conserving surgery (BCS). The issue that merits consideration for oncologic safety and cost-effectiveness about the modalities to assure clear margins at initial surgical intervention remains controversial after neo-adjuvant chemotherapy (NAC). The presented study aimed to assess the impact of intraoperative ultrasound (IOUS)-guided surgery on accurate localization of tumor site, adequacy of excision with clear margins, and healthy tissue sacrifice in BCS after NAC. Patients who had IOUS-guided BCS ater NAC were reviewed. No patient had preoperative localization with wire or radiotracer. Intraoperative real-time sonographic localization, sonographic margin assessment during resection, macroscopic and sonographic examination of specimen, and cavity shavings (CS) were done as the standard procedure. No frozen assessment was performed. One hundred ninety-four patients were included, in which 42.5% had pCR. IOUS-guided surgery accomplished successful localization of the targeted lesions in all patients. Per protocol, all inked margins on CS specimens were reported to be tumor-free in permanent histopathology. No re-excision or mastectomy was required. For a setting without CS, the negative predictive value (NPV) of IOUS rate was 96%. IOUS was found to over and underestimate tumor response to NAC both in 2% of patients. IOUS-guided surgery seems to be an efficient modality to perform adequate BCS after NAC with no additional localization method. Especially, when CS is integrated as a standard to BCS, IOUS seems to provide safe surgery for patients with no false negativity and a high rate of NPV.