First Surgical National Consensus Conference of the Italian Breast Surgeons association (ANISC) on breast cancer management in neoadjuvant setting: Results and summary.

RATIONALE: On October 15th, 2020, the first Surgical National Consensus Conference on neoadjuvant chemotherapy (NACT) was promoted by the Italian Association of Breast Surgeons (ANISC). METHOD: The Consensus Conference was entirely held online due to anti-Covid-19 restrictions and after an introductory four lectures held by national and international experts in the field, a total of nine questions were presented and a digital "real-time" voting system was obtained. A consensus was reached if 75% or more of all panelists agreed on a given question. RESULTS: A total of 202 physicians, from 76 different Italian Breast Centers homogeneously distributed throughout the Italian country, participated to the Conference. Most participants were surgeons (75%). Consensus was reached for seven out of the nine considered topics, including management of margins and lymph nodes at surgery, and there was good correspondence between the 32 "Expert Panelists" and the "Participants" to the Conference. Consensus was not achieved regarding the indications to NACT for high-grade luminal-like breast tumors, and the need to perform an axillary lymph node dissection in case of micrometastases in the sentinel lymph node after NACT. CONCLUSIONS: NACT is a topic of major interest among surgeons, and there is need to develop shared guidelines. While a Consensus was obtained for most issues presented at this Conference, controversies still exist regarding indications to NACT in luminal B-like tumors and management of lymph node micrometastases. There is need for clinical studies and analysis of large databases to improve our knowledge on this subject.

Curative-intent Metastasis-directed Therapies for Molecularly-defined Oligorecurrent Prostate Cancer: A Prospective Phase II Trial Testing the Oligometastasis Hypothesis.

BACKGROUND: The hypothesis of a curable oligometastatic prostate cancer (PCa) state remains to be clinically-proven. Conventional imaging often fails to localize early recurrences, hampering the potential for radical approaches. OBJECTIVE: We hypothesize that prostate-specific membrane antigen (PSMA)-targeted PET-MR/CT allows for earlier detection and localization of oligorecurrent-PCa, unveiling a molecularly-defined state amenable to curative-intent metastasis-directed treatment (MDT). DESIGN/SETTING/PARTICIPANTS: Single-institution single-arm phase-two study. Patients with rising PSA (0.4-3.0 ng/mL) after maximal local therapy (radical prostatectomy and post-operative radiotherapy), negative conventional staging, and no prior salvage hormonal therapy (HT) were eligible. INTERVENTIONS: All patients underwent [18F]DCFPyL PET-MR/CT. Patients with molecularly-defined oligorecurrent-PCa had MDT (stereotactic ablative body radiotherapy [SABR] or surgery) without HT. OUTCOME MEASUREMENTS/STATISTICAL ANALYSIS: Primary endpoint was biochemical response (complete, i.e. biochemical 'no evidence of disease' [bNED], or partial response [100% or ≥50% PSA decline from baseline, respectively]) after MDT. Simon's two-stage design was employed (null and alternate hypotheses <5% and >20% response rate, respectively), with α and ß of 0.1. RESULTS: Seventy-two patients were enrolled (May/2017-July/2019). Thirty-eight (53%) had PSMA-detected oligorecurrent-PCa amenable for MDT. Thirty-seven (51%) agreed to MDT: 10 and 27 underwent surgery and SABR, respectively. Median follow-up was 15.9 months (IQR 9.8-19.1). Of patients receiving MDT, the overall response rate was 60%, including 22% rendered bNED. One (2.7%) grade 3 toxicity (intra-operative ureteric injury) was observed. CONCLUSIONS: PSMA-defined oligorecurrent-PCa can be rendered bNED, a necessary step towards cure, in 1 of 5 patients receiving MDT alone. Randomized trials are justified to determine if MDT +/- systemic agents can expand the curative therapeutic armamentarium for PCa. PATIENT SUMMARY: We studied men treated for prostate cancer with rising PSA. We found PSMA imaging detected recurrent cancer in three-quarters of patients, and targeted treatment to these areas significantly decreased PSA in half of patients.

Benefit of a more extended pelvic lymph node dissection among patients undergoing radical prostatectomy for localized prostate cancer: A causal mediation analysis.

BACKGROUND: The therapeutic role of extended (ePLND) versus nonextended pelvic lymph node dissection (nePLND) to remove occult micrometastases in men undergoing radical prostatectomy for localized prostate cancer (PC) is conflicting. Therefore, our aim was to quantify the direct effect of ePLND versus nePLND (removal of occult micrometastases), which is not mediated through the detection of nodal disease and potential adjuvant therapy (indirect effect). METHODS: Retrospective, bi-center cohort study of consecutive patients undergoing radical prostatectomy and PLND for PC (January 2006 and December 2016). Patients were followed until April 2018 for the occurrence of either biochemical recurrence or secondary therapy (composite outcome). ePLND was compared to nePLND by unweighted and weighted survival analysis (total effect) as well as by causal mediation analysis (direct and indirect effect). RESULTS: Positive nodal disease was detected in 71 (7%) out of 1008 patients undergoing radical prostatectomy and PLND for PC (ePLND: 368 [36.5%]; nePLND: 640 [63.5%]). Survival analysis demonstrated results in favor of ePLND (unweighted hazard ratio: 0.77 [95% confidence interval: 0.59-1.01], p = .056; weighted hazard ratio: 0.75 [0.56-0.99], p = .044). The causal mediation analysis confirmed the total effect of 0.77 (0.71-0.82). After disentangling this total effect into an indirect effect (via detection of nodal disease and potential adjuvant therapy) and a direct effect (via removal of occult micrometastases), we identified an even more protective direct effect of 0.69 (0.63-0.75). CONCLUSIONS: Our results not only indicate the utility of ePLND but also that its impact is not restricted to a staging benefit and probably involves a therapeutic benefit mediated through the removal of occult micrometastases.

Is it possible to intraoperatively modulate the extent of thyroidectomy in small papillary thyroid carcinoma?

BACKGROUND: Thyroid lobectomy is the preferred option for small, unifocal papillary thyroid carcinoma. Involvement of the central neck lymph nodes is an indication for total thyroidectomy plus central neck dissection. We aimed to verify if frozen section examination of ipsilateral central neck nodes can identify the subgroup of patients scheduled for thyroid lobectomy intraoperatively who could benefit of more extensive initial operative treatment. METHODS: Ninety-four consenting patients with clinically unifocal cN0 papillary thyroid carcinoma underwent thyroid lobectomy plus ipsilateral central neck dissection with frozen section examination. If the frozen section examination was positive for metastases, a completion thyroidectomy and a bilateral central neck dissection were accomplished during the same procedure. RESULTS: Frozen section examination identified occult nodal metastases in 25 of the 94 patients who then underwent immediate completion thyroidectomy and bilateral central neck dissection. Overall, central neck node metastases were found at final histology in 35 cases: occult micrometastases were observed in additional 9 patients and nodal metastases ≥2 mm in additional 1 patient. CONCLUSION: Intraoperative assessment of nodal status obtained with ipsilateral central neck dissection and frozen section examination is able to change the extent of thyroidectomy in about one-fourth of patients scheduled for thyroid lobectomy. Frozen section examination appears a safe and effective strategy to decrease the need of a second-step completion procedure and, theoretically, the risk of recurrence.

Stage IIIa Melanoma and Impact of Multiple Positive Lymph Nodes on Survival.

BACKGROUND: For patients with cutaneous melanoma, having >1 positive lymph node (LN) is associated with worse survival. We hypothesized that for stage IIIA patients, N2a disease (2 to 3 positive LN) would be associated with a worse prognosis compared to those with N1a disease (1 positive LN). STUDY DESIGN: Stage IIIA melanoma patients in the NCDB Participant User File from 2010 to 2016 were analyzed. Overall survival (OS) between N1a and N2a patients was compared. Subgroup analyses were made between patients undergoing sentinel lymph node (SLN) biopsy alone and those undergoing subsequent completion lymph node dissection (CLND). A separate post hoc analysis of T2a patients undergoing SLN biopsy and CLND from a prospective multicenter randomized clinical trial was performed to validate the findings. RESULTS: Records of 2,305 IIIA patients were evaluated. In an adjusted survival model, N2a disease was an independent risk factor for worse OS (hazard ratio [HR] 1.56, p = 0.0052). In the subgroup analysis, there was no difference in OS between N1a and N2a disease for patients who underwent SLN biopsy without CLND (p = 0.59), but there was a significant difference in OS for patients who underwent SLN biopsy plus CLND (p = 0.0009). The separate clinical trial database confirmed that for patients with SLN-only disease, there was no difference in OS between N1a and N2a disease. CONCLUSIONS: For stage IIIA melanoma patients, the distribution of micrometastatic lymph node disease (SLN or non-SLN), rather than the absolute number of SLNs, should be considered when individualizing adjuvant therapy recommendations.

The impact of low-volume metastasis on disease-free survival of women with early-stage cervical cancer.

PURPOSE: We aimed to assess the impact of low-volume metastasis (micrometastasis and isolated tumor cells) on disease-free survival (DFS) of women with early-stage cervical cancer. METHODS: Women with clinically suspected stage 1A-IB2 (FIGO 2018 classification) disease who underwent retroperitoneal nodal staging between October 2010 and April 2018, were retrospectively analyzed. The group of women who had undergone lymphadenectomy and standard node pathologic analysis (H&E group), were compared to the group undergoing sentinel node mapping (SLN) and ultrastaging with or without lymphadenectomy (ultrastaging group). At a median follow-up of 45 months, the DFS curves were analyzed. RESULTS: Overall, 573 patients were revised (272 in the H&E group and 302 in the ultrastaging group). Eighty-five patients presented lymph node metastasis (32 in H&E, 53 in ultrastaging). Ultrastaging protocol increased the rate of low-volume metastasis by 5.6%. Twenty patients showed exclusive micrometastasis or ITC's. Seventy-three recurrences occurred (35 in H&E, 38 in ultrastaging). Only 1 out of 53 patients in the ultrastaging group (1.9%) presented with micrometastasis recurred. The 3-year disease-free survival was 89% for the H&E group, and 88% for the ultrastaging group, respectively (p = 0.175). CONCLUSION: Ultrastaging analysis allowed increasing the detection of low volume metastasis in women with early-stage cervical cancer. However, the type of nodal staging did not have an impact on patients' 3-year disease-free survival.

Development of a clinically relevant ovarian cancer model incorporating surgical cytoreduction to evaluate treatment of micro-metastatic disease.

OBJECTIVES: Mouse models of ovarian cancer commonly transfer large numbers of tumor cells into the peritoneal cavity to establish experimental metastatic disease, which may not adequately model early metastatic spread from a primary tumor site. We hypothesized we could develop an ovarian cancer model that predictably represents micro-metastatic disease. METHODS: Murine ID8VEGF ovarian cancer cells were transduced to express enhanced luciferase (eLuc) to enable intravital detection of microscopic disease burden and injected beneath the ovarian bursa of C57Bl/6 mice. At 6 or 10 weeks after orthotopic injection, when mice had detectable metastases, hysterectomy and bilateral salpingo-oophorectomy was performed to remove all macroscopic disease, and survival monitored. Immunohistochemistry and gene expression profiling were performed on primary and metastatic tumors. RESULTS: eLuc-transduced ID8VEGF cells were brighter than cells transduced with standard luciferase, enabling in vivo visualization of microscopic intra-abdominal metastases developing after orthotopic injection. Primary surgical cytoreduction removed the primary tumor mass but left minimal residual disease in all mice. Metastatic sites that developed following orthotopic injection were similar to metastatic human ovarian cancer sites. Gene expression and immune infiltration were similar between primary and metastatic mouse tumors. Surgical cytoreduction prolonged survival compared to no surgery, with earlier cytoreduction more beneficial than delayed, despite micro-metastatic disease in both settings. CONCLUSIONS: Mice with primary ovarian tumors established through orthotopic injection develop progressively fatal metastatic ovarian cancer, and benefit from surgical cytoreduction to remove bulky disease. This model enables the analysis of therapeutic regimens designed to target and potentially eradicate established minimal residual disease.

Systemic and tumor-directed therapy for oligometastatic prostate cancer: study protocol for a phase II trial for veterans with de novo oligometastatic disease.

BACKGROUND: The treatment paradigm for metastatic hormone-sensitive prostate cancer (mHSPC) patients is evolving. PET/CT now offers improved sensitivity and accuracy in staging. Recent randomized trial data supports escalated hormone therapy, local primary tumor therapy, and metastasis-directed therapy. The impact of combining such therapies into a multimodal approach is unknown. This Phase II single-arm clinical trial sponsored and funded by Veterans Affairs combines local, metastasis-directed, and systemic therapies to durably render patients free of detectable disease off active therapy. METHODS: Patients with newly-diagnosed M1a/b prostate cancer (PSMA PET/CT staging is permitted) and 1-5 radiographically visible metastases (excluding pelvic lymph nodes) are undergoing local treatment with radical prostatectomy, limited duration systemic therapy for a total of six months (leuprolide, abiraterone acetate with prednisone, and apalutamide), metastasis-directed stereotactic body radiotherapy (SBRT), and post-operative fractionated radiotherapy if pT ≥ 3a, N1, or positive margins are present. The primary endpoint is the percent of patients achieving a serum PSA of < 0.05 ng/mL six months after recovery of serum testosterone ≥150 ng/dL. Secondary endpoints include time to biochemical progression, time to radiographic progression, time to initiation of alternative antineoplastic therapy, prostate cancer specific survival, health related quality-of-life, safety and tolerability. DISCUSSION: To our knowledge, this is the first trial that tests a comprehensive systemic and tumor directed therapeutic strategy for patients with newly diagnosed oligometastatic prostate cancer. This trial, and others like it, represent the critical first step towards curative intent therapy for a patient population where palliation has been the norm. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03298087 (registration date: September 29, 2017).

Toxicity evaluation of magnetic hyperthermia induced by remote actuation of magnetic nanoparticles in 3D micrometastasic tumor tissue analogs for triple negative breast cancer.

Magnetic hyperthermia as a treatment modality is acquiring increased recognition for loco-regional therapy of primary and metastatic lung malignancies by pulmonary delivery of magnetic nanoparticles (MNP). The unique characteristic of magnetic nanoparticles to induce localized hyperthermia in the presence of an alternating magnetic field (AMF) allows for preferential killing of cells at the tumor site. In this study we demonstrate the effect of hyperthermia induced by low and high dose of MNP under the influence of an AMF using 3D tumor tissue analogs (TTA) representing the micrometastatic, perfusion independent stage of triple negative breast cancer (TNBC) that infiltrates the lungs. While application of inhalable magnetic nanocomposite microparticles or magnetic nanocomposites (MnMs) to the micrometastatic TNBC model comprised of TTA generated from cancer and stromal cells, showed no measureable adverse effects in the absence of AMF-exposure, magnetic hyperthermia generated under the influence of an AMF in TTA incubated in a high concentration of MNP (1 mg/mL) caused significant increase in cellular death/damage with mechanical disintegration and release of cell debris indicating the potential of these inhalable composites as a promising approach for thermal treatment of diseased lungs. The novelty and significance of this study lies in the development of methods to evaluate in vitro the application of inhalable composites containing MNPs in thermal therapy using a physiologically relevant metastatic TNBC model representative of the microenvironmental characteristics in secondary lung malignancies.

[The Impact of Tumor Cell Proliferation on Occult Micrometastases, Tumor Recurrence and Patient Outcome Following Resection for Liver Malignancies]. / Stellenwert des Proliferationsreizes auf die okkulte Mikrometastasierung sowie Rezidivhäufigkeit und Prognose nach Resektion von Lebermalignomen.

Liver resection is currently considered to be essential part of the curative treatment of primary and secondary liver malignancies. However, long-term survival in these patients is limited by the high incidence of tumor recurrence. Recent clinical and experimental studies have indicated that cellular and molecular mechanisms associated with liver regeneration after partial hepatectomy may have a proliferative effect on occult micrometastases and circulating tumor cells and are thus responsible for recurrent disease. Growth factors and cytokines involved in liver regeneration have also been shown to influence tumour growth and metastasis. However, the underlying mechanisms explaining the interactions between regenerating liver tissue and tumour cell proliferation remain unclear. The development of modern agents specifically targeting these processes may improve disease-free and overall survival rates after oncological hepatectomy.

Therapeutic Advances in Localized Pancreatic Cancer.

IMPORTANCE: It is estimated that pancreatic cancer (PC) will become the second leading cause of cancer-related death in the United States by 2030. OBSERVATIONS: Clinical and preclinical data support the understanding that PC metastases occur early in the pathogenesis of this disease, even before the primary tumor can be detected. This has important implications for the clinical management of patients with localized PC, as surgery alone is unlikely to be curative for most patients. The delivery of postoperative adjuvant therapy is problematic in this disease because of the magnitude of the operation needed to remove the primary tumor, which can affect patient recovery and delay (sometimes indefinitely) the delivery of systemic therapy. For these reasons, the use of chemotherapy and/or chemoradiation prior to surgery (neoadjuvant therapy) is increasingly recognized as the preferred strategy for treatment sequencing. Neoadjuvant therapy is recommended for patients with borderline resectable PC and, at some centers, neoadjuvant therapy has been extended to patients with resectable PC as well. Importantly, therapeutic advances in multidrug systemic therapy and radiation therapy have already been adopted in the neoadjuvant setting where treatment toxicity will not be compounded by surgical recovery. In addition, the use of local-regional therapies in highly selected patients with locally advanced PC, following a prolonged period of induction systemic therapy, will be an area of intense scrutiny. Future improvements in diagnostic biomarkers may allow for real-time sequencing of multimodality therapy for individual patients based on a more accurate and timely assessment of treatment response. CONCLUSIONS AND RELEVANCE: Neoadjuvant treatment sequencing allows patients to receive multimodality therapy in a manner that prioritizes early exposure to systemic therapy to maximize the treatment of micrometastatic disease in an immune-competent host prior to surgical intervention. Patients who complete all intended neoadjuvant therapy, including surgery, experience an overall survival benefit that is unmatched by a surgery-first approach.

Model-based genotype-phenotype mapping used to investigate gene signatures of immune sensitivity and resistance in melanoma micrometastasis.

In this paper, we combine kinetic modelling and patient gene expression data analysis to elucidate biological mechanisms by which melanoma becomes resistant to the immune system and to immunotherapy. To this end, we systematically perturbed the parameters in a kinetic model and performed a mathematical analysis of their impact, thereby obtaining signatures associated with the emergence of phenotypes of melanoma immune sensitivity and resistance. Our phenotypic signatures were compared with published clinical data on pretreatment tumor gene expression in patients subjected to immunotherapy against metastatic melanoma. To this end, the differentially expressed genes were annotated with standard gene ontology terms and aggregated into metagenes. Our method sheds light on putative mechanisms by which melanoma may develop immunoresistance. Precisely, our results and the clinical data point to the existence of a signature of intermediate expression levels for genes related to antigen presentation that constitutes an intriguing resistance mechanism, whereby micrometastases are able to minimize the combined anti-tumor activity of complementary responses mediated by cytotoxic T cells and natural killer cells, respectively. Finally, we computationally explored the efficacy of cytokines used as low-dose co-adjuvants for the therapeutic anticancer vaccine to overcome tumor immunoresistance.

Differences in metastatic patterns in relation to time between primary surgery and first relapse from breast cancer suggest synchronized growth of dormant micrometastases.

A significant variation in the metastatic pattern among breast cancer patients exists. Clinical observations suggest that these differences are related to time to recurrence (TTR), thus suggesting a common systemic growth signal at the time of surgery. Our goal was to identify a marker for synchronized growth of micrometastases. To quantify the metastatic pattern at first relapse, 180 patients with metastatic breast cancer were studied. Standard deviation (SD) of lesions size and lesion number was calculated and served as a marker for variation. Patients with low SD (multiple/similar sized lesions) were assumed to have synchronized growth, whereas patients with high SD were assumed to have unsynchronized growth. Patients were grouped according to TTR; early (< 3 years-) or late (> 3 years- after surgery). In patients not receiving systemic adjuvant treatment, median SD was significantly lower in the early group (2.5 mm) compared with 6.4 mm in the late group (p = 0.005). In node negative patients, median SD was significantly lower in the early group (3.0 mm) when compared with the late group (5.7 mm, p = 0.02). An additional drop in SD was observed immediately after end of adjuvant endocrine therapy. Our results identify SD as a marker of synchronized metastatic growth in breast cancer. A metastatic phenotype characterized by multiple similar sized metastases, suggesting synchronized onset of growth of micrometastases was predominantly found in patients recurring early after surgery and was counteracted by adjuvant treatment. Systemic growth signals caused by surgery might be antagonized during the time window following surgery.

Breast cancer micrometastasis and axillary sentinel lymph nodes frozen section. Our experience and review of literature.

BACKGROUND: Sentinel lymph node (SLN) biopsy plays a major role in the surgical management of primary breast cancer. The aim of this study was to assess the diagnostic accuracy of the assessment of axillary frozen sections of SLNs for micrometastasis diagnosis. PATIENTS AND METHODS: This study focused on 250 SLNs from 137 patients. Each lymph node was fully analyzed by frozen section. After fixation, serial sections were cut and stained by hematoxylin and eosin (HE) and for pan-cytokeratins by immunohistochemistry (IHC). RESULTS: Tumor cells were detected in 57 SLNs, 37 on frozen sections and 20 on controls. Of these 57 positive SLNs, 38 contained metastases, 9 contained micrometastases and 10 contained isolated tumor cells. The specificity and positive predictive value of SLN frozen sections for micrometastasis was 100%. The sensitivity was 83.3% for metastasis, 40% for micrometastasis; the false-negative rate was 16.7% for metastasis and 60% for micrometastasis. CONCLUSION: Analysis of frozen section of SLNs is an accurate method for metastasis detection, allowing concurrent axillary dissection when positive. The protocol for SLN analyses described herein shows good sensitivity for micrometastasis detection.

Inhibition of tumor necrosis factor alpha reduces the outgrowth of hepatic micrometastasis of colorectal tumors in a mouse model of liver ischemia-reperfusion injury.

BACKGROUND: Patients with colorectal cancer (CRC) often develop liver metastases, in which case surgery is considered the only potentially curative treatment option. However, liver surgery is associated with a risk of ischemia-reperfusion (IR) injury, which is thought to promote the growth of colorectal liver metastases. The influence of IR-induced tumor necrosis factor alpha (TNF-α) elevation in the process still is unknown. To investigate the role of TNF-α in the growth of pre-existing micrometastases in the liver following IR, we used a mouse model of colorectal liver metastases. In this model, mice received IR treatment seven days after intrasplenic injections of colorectal CT26 cells. Prior to IR treatment, either TNF-α blocker Enbrel or low-dose TNF-α, which could inhibit IR-induced TNF-α elevation, was administered by intraperitoneal injection. RESULTS: Hepatic IR treatment significantly promoted CT26 tumor growth in the liver, but either Enbrel or low-dose TNF-α pretreatment reversed this trend. Further studies showed that the CT26 + IR group prominently increased the levels of ALT and AST, liver necrosis, inflammatory infiltration and the expressions of hepatic IL-6, MMP9 and E-selectin compared to those of CT26 group. Inhibition of TNF-α elevation remarkably attenuated the increases of these liver inflammatory damage indicators and tumor-promoting factors. CONCLUSION: These findings suggested that inhibition of TNF-α elevation delayed the IR-enhanced outgrowth of colorectal liver metastases by reducing IR-induced inflammatory damage and the formation of tumor-promoting microenvironments. Both Enbrel and low-dose TNF-α represented the potential therapeutic approaches for the protection of colorectal liver metastatic patients against IR injury-induced growth of liver micrometastases foci.

[Breast cancer and axillary area: state of the art and perspectives]. / Cancer du sein et creux axillaire : état de l'art et perspectives.

A therapeutic surgical de-escalation has been observed since many years with an actual prolongation for axillary lymph node area treatment. Axillary lymph node dissection (ALND) omission has been studied before and after validation of sentinel node (SN) biopsy procedure. A non-inferiority of ALND omission has been reported in case of non-involved SN. ALND omission has been studied in case of SN involvement without consensus in relation with scientific level of proof and with selective indications. The purpose of this work is to make a synthesis of the experiences on this subject then to envisage the current and future perspectives.

[Clinical significance of lymph node micrometastases in cervical cancer]. / Kliniczne znaczenie mikroprzerzutów w wezlach chlonnych w raku szyjki macicy.

In most cancers of epithelial origin, metastases to the lymph nodes constitute the most important prognostic factor and are predictive of the results of the surgical and adjuvant therapies. Data on the lymph node status allows to design an appropriate treatment plan. Despite advances in gynecologic oncology the importance of lymph node micrometastases in cervical cancer especially in nonsentinel lymph nodes which are detected by ultrastaging, has not been fully elucidated. The purpose of the article is to familiarize the reader with the state of current knowledge on cervical cancer micrometastases. The authors attempt to answer the question about the benefits of lymph node assessment in the search for micrometastases in cervical cancer as well as to address emerging doubts.