Molecular image-guided surgery in gynaecological cancer: where do we stand?

PURPOSE: The aim of this review is to give an overview of the current status of molecular image-guided surgery in gynaecological malignancies, from both clinical and technological points of view. METHODS: A narrative approach was taken to describe the relevant literature, focusing on clinical applications of molecular image-guided surgery in gynaecology, preoperative imaging as surgical roadmap, and intraoperative devices. RESULTS: The most common clinical application in gynaecology is sentinel node biopsy (SNB). Other promising approaches are receptor-target modalities and occult lesion localisation. Preoperative SPECT/CT and PET/CT permit a roadmap for adequate surgical planning. Intraoperative detection modalities span from 1D probes to 2D portable cameras and 3D freehand imaging. CONCLUSION: After successful application of radio-guided SNB and SPECT, innovation is leaning towards hybrid modalities, such as hybrid tracer and fusion of imaging approaches including SPECT/CT and PET/CT. Robotic surgery, as well as augmented reality and virtual reality techniques, is leading to application of these innovative technologies to the clinical setting, guiding surgeons towards a precise, personalised, and minimally invasive approach.

TRImodal DEfinitive invasive vagiNal carcinoma Treatment (TRIDENT protocol): how a standardized approach may change prognostic outcomes.

OBJECTIVE: Vaginal carcinoma is a rare malignancy accounting for 1-2% of all gynecological cancers. Surgery has a limited role, while definitive radiotherapy-chemotherapy followed by interventional radiotherapy is considered a valid alternative. The aim of the TRIDENT (TRImodal DEfinitive invasive vagiNal carcinoma Treatment) pilot study was to report the results of a modern standardized trimodal protocol treatment consisting of image guided definitive radiotherapy-chemotherapy followed by image guided interventional radiotherapy in terms of safety and efficacy. METHODS: Between January 2019 and December 2021, we analyzed 21 consecutive patients with primary vaginal cancer who had received radiotherapy-chemotherapy followed by interventional radiotherapy. The primary study endpoint was local control, and secondary endpoints were metastasis free survival, overall survival, and rate and severity of acute and late toxicities. RESULTS: 14 patients had FIGO (International Federation of Gynecology and Obstetrics) stage II, five patients had stage III, and two had stage IVB disease. Median total external beam radiotherapy dose for the tumor was 45 Gy. Median total dose on positive nodes was 60 Gy. Median total dose for interventional radiotherapy was 28 Gy over four high dose rate fractions to achieve between 85 and 95 Gy equivalent dose, in 2 Gy fractions (EQD2)α/ß10, to the high risk clinical target volume, and 60 Gy EQD2α/ß10 to the intermediate risk clinical target volume. All patients received weekly platinum based chemotherapy. Median follow-up was 20 months (range 10-56 months). Two year actuarial local control, metastasis free survival, and overall survival rate were 79.4%, 90.5%, and 79.4%, respectively. In terms of acute toxicity, there were no grade 4 events and only one acute grade (G) 3 toxicity (skin). Only vaginal stenosis (G3) was documented 12 months after therapy due to late toxicity. CONCLUSIONS: In this study, definitive radiotherapy-chemotherapy followed by interventional radiotherapy was a safe and effective treatment modality for primary vaginal cancer.

Definitive chemoradiation in vulvar squamous cell carcinoma: outcome and toxicity from an observational multicenter Italian study on vulvar cancer (OLDLADY 1.1).

BACKGROUND: Vulvar carcinoma is a rather uncommon gynecological malignancy affecting elderly women and the treatment of loco-regional advanced carcinoma of the vulva (LAVC) is a challenge for both gynecologic and radiation oncologists. Definitive chemoradiation (CRT) is the treatment of choice, but with disappointing results. In this multicenter study (OLDLADY-1.1), several institutions have combined their retrospective data on LAVC patients to produce a real-world dataset aimed at collecting data on efficacy and safety of CRT. METHODS: The primary study end-point was 2-year-local control (LC), secondary end-points were 2-year-metastasis free-survival (MFS), 2-year-overall survival (OS) and the rate and severity of acute and late toxicities. Participating centers were required to fill data sets including age, stage, histology, grading as well as technical/dosimetric details of CRT. Data about response, local and regional recurrence, acute and late toxicities, follow-up and outcome measures were also collected. The toxicity was a posteriori documented through the Common Terminology Criteria for Adverse Events version 5 scale. RESULTS: Retrospective analysis was performed on 65 patients with primary or recurrent LAVC treated at five different radiation oncology institutions covering 11-year time interval (February 2010-November 2021). Median age at diagnosis was 72 years (range 32-89). With a median follow-up of 19 months (range 1-114 months), 2-year actuarial LC, MFS and OS rate were 43.2%, 84.9% and 59.7%, respectively. In 29 patients (44%), CRT was temporarily stopped (median 5 days, range 1-53 days) due to toxicity. The treatment interruption was statistically significant at univariate analysis of factors predicting LC (p: 0.05) and OS rate (p: 0.011), and it was confirmed at the multivariate analysis for LC rate (p: 0.032). In terms of toxicity profile, no G4 event was recorded. Most adverse events were reported as grade 1 or 2. Only 14 acute G3 toxicities, all cutaneous, and 7 late G3 events (3 genitourinary, 3 cutaneous, and 1 vaginal stenosis) were recorded. CONCLUSION: In the context of CRT for LAVC, the present study reports encouraging results even if there is clearly room for further improvements, in terms of both treatment outcomes, toxicity and treatment interruption management.

Lymphatic mapping and sentinel node biopsy in vulvar melanoma: the first multicenter study and systematic review.

OBJECTIVE: This multicenter study aimed to investigate the role of preoperative lymphatic mapping and sentinel node biopsy (SNB) as well as the impact of negative SNB on loco-regional control and survival in vulvar melanoma patients with clinically negative nodes (cN0). METHODS: Patients who had a proven vulvar melanoma with a Breslow thickness of 1-4 mm, cN0 and underwent a preoperative lymphatic mapping followed by SNB between July 2013 and March 2021 were retrospectively included. Groin recurrence and mortality rate were calculated as absolute and relative frequency. Disease-free survival (DFS) and overall survival (OS) were assessed by the Kaplan-Meier method. We provided a systematic review, searching among PubMed/Medline and Embase libraries. A total of 6 studies were identified (48 patients). RESULTS: A total of 18 women were included. Preoperative planar images showed 51 SNs in 28 groins. Additional SPECT/CT images were acquired in 5/18 cases; SNs were identified pre- and intra-operatively in all cases. A total of 65 SNs were excised from 28 groins. A total of 13/18 (72.2%) patients (21/28 groins, 75%) had negative SNs with no groin recurrences and 12/13 (92.3%) were still alive at last follow-up. Five out of the 18 (27.8%) patients (7/28 groins, 25%) had positive SNs, 2/5 (40%) patients died of cancer after 26.2 and 33.8 months, respectively. The median DFS and OS for the entire cohort were 17.9 months (95% CI, 10.3-19.9) and 65.0 months (95% CI, 26.2-infinite), respectively. The probability of DFS and OS at 3 years were 15.5% (95% CI, 2.6-38.7) and 64.3% (95% CI, 15.5-90.2), respectively. CONCLUSIONS: The use of preoperative lymphatic mapping followed by SNB permits a precise and minimally invasive surgical approach in cN0 vulvar melanoma patients. Negative SNB is associated with low risk of groin relapse and good survival.

Electrochemotherapy with intravenous bleomycin for heavily pre-treated vulvar cancer patients.

OBJECTIVE: The management of vulvar cancer recurrences is complicated by patients' advanced age and comorbidities. Bleomycin-based electrochemotherapy is a potential treatment option in this setting. However, no data on long-term outcomes are available. Therefore, a multicenter observational study was designed to evaluate the 5-year results in these patients. METHODS: Data about patients and tumor characteristics, electrochemotherapy cycles, clinical response, and follow-up were recorded. Treatment procedures were performed according to the European Standard Operating Procedures of Electrochemotherapy (ESOPE) guidelines. Response was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. RESULTS: Fifty-one patients (mean age 82.31±7.28 years) with squamous cell vulvar cancer underwent electrochemotherapy (median number of sessions 1; range 1-4). 20 patients had complete response and 32% of these were disease-free after 2 years (median progression-free survival 16.8 months). In 13 patients with partial response the median progression-free survival was 15.36 months, while patients with stable or progressive disease showed tumor relapse after 6.95 and 3.26 months, respectively (p<0.001). Median overall survival was 18.77, 13.07, 6.73, and 11.13 months in patients with complete response, partial response, stable disease, and progressive disease, respectively (p=0.001). CONCLUSION: Long-term follow-up of vulvar cancer patients showed reasonable tumor control after electrochemotherapy and improved progression-free survival and overall survival in responder subjects compared with non-responders. Further studies aimed at improving local response after electrochemotherapy are warranted. Thus, this approach represents a potential alternative for these patients.

European Society of Gynaecological Oncology Guidelines for the Management of Patients with Vulvar Cancer - Update 2023.

BACKGROUND: As part of its mission to improve the quality of care for women with gynecological cancers across Europe, the European Society of Gynaecological Oncology (ESGO) first published in 2017 evidence-based guidelines for the management of patients with vulvar cancer. OBJECTIVE: To update the ESGO guidelines based on the new evidence addressing the management of vulvar cancer and to cover new topics in order to provide comprehensive guidelines on all relevant issues of diagnosis and treatment of vulvar cancer. METHODS: The ESGO Council nominated an international development group comprised of practicing clinicians who provide care to vulvar cancer patients and have demonstrated leadership through their expertize in clinical care and research, national and international engagement and profile as well as dedication to the topics addressed to serve on the expert panel (18 experts across Europe). To ensure that the statements were evidence-based, new data identified from a systematic search were reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Prior to publication, the guidelines were reviewed by 206 international practitioners in cancer care delivery and patient representatives. RESULTS: The updated guidelines cover comprehensively diagnosis and referral, staging, pathology, pre-operative investigations, surgical management (local treatment, groin treatment, sentinel lymph node procedure, reconstructive surgery), (chemo)radiotherapy, systemic treatment, treatment of recurrent disease (vulvar, inguinal, pelvic, and distant recurrences), and follow-up. Management algorithms are also defined.

Trans-inguinal pelvic lymphadenectomy in vulvar cancer patients: TRIPLE pilot study.

OBJECTIVE: The goal of this study was to assess the feasibility and safety of a retrograde extraperitoneal trans-inguinal novel approach to pelvic lymphadenectomy in vulvar cancer patients. The secondary objectives were to assess complications (early and late) and oncological outcomes. METHODS: In this pilot study, all patients referred to our institution from November 2019 to May 2021 were evaluated. The inclusion criteria were patients diagnosed with primary/recurrent vulvar cancer and who were candidates for concomitant groin and pelvic lymph node dissection. A consecutive sampling was planned during the study period. After conventional inguino-femoral lymph nodal dissection, ipsilateral extraperitoneal trans-inguinal pelvic lymphadenectomy (TRIPLE) was performed through a groin incision. Clinical data, type of treatment, perioperative complications, and follow-up were evaluated. RESULTS: 13 patients (8 primary, 5 recurrent vulvar cancer) underwent 16 TRIPLE procedures (10 unilateral, 3 bilateral). The median age was 69 years (range 58-93 years); 8 patients had comorbidities (61.5%). Up front locoregional radiotherapy was previously performed in two cases (15.4%). The pathology report showed metastatic lymph nodes in 20 (87%) groins and 11 (68.8%) pelvic sites; the mean number of removed and metastatic pelvic lymph nodes was 12.1 (range 5-33) and 2.9 (range 0-18), respectively. No intra-operative site-specific complications occurred. One (5.9%) post-operative site-specific complication was reported (pelvic abscess, grade 2), which was treated with antibiotics. One patient died due to concomitant pneumonia. No unilateral pelvic lymph node recurrence occurred during follow-up (median 13 months, range 2-43 months); 3 patients (23.1%) had distant site recurrence (median disease-free survival 9 months). CONCLUSIONS: TRIPLE seems to be a feasible and safe technique, providing adequate lymph node dissection. Despite being a high-risk and fragile population, morbidity was similar to previously reported data for conventional mini-invasive approaches. Prospective larger comparative series are necessary.

Clinical impact of SARS-CoV-2 infection among patients with vulvar cancer: the Gemelli Vul.Can multidisciplinary team.

BACKGROUND: 'Severe acute respiratory syndrome coronavirus-2' (SARS-CoV-2) infection has dramatically affected the management of patients with cancer, who are most vulnerable to the consequences of the infection. Patients with vulvar cancer are frequently elderly and affected by multiple co-morbidities, thus representing a particularly frail population. OBJECTIVE: To assess the clinical impact of the SARS-CoV-2 infection among patients scheduled for treatment for active vulvar cancer. METHODS: Data on patients with vulvar tumors referred to Fondazione Policlinico Universitario Agostino Gemelli IRCCS between February 2020 and July 2021 were retrospectively analyzed. Patients with a positive reverse transcription polymerase chain reaction in nasopharyngeal swab were considered as positive for SARS-Cov-2. RESULTS: One hundred and ninety-one patients with vulvar cancer were evaluated and scheduled for treatment. The median age was 72 years (range 35-94). Seven (3.7%) patients were diagnosed with SARS-Cov-2 infection: three (42.9%) had their treatment delayed, with no apparent consequences, two (28.6%) had their treatment delayed and later abandoned because of clinical worsening due to oncologic disease progression, and two (28.6%) contracted the infection in the post-operative period and died due to respiratory complications. CONCLUSIONS: In most cases the infection had major clinical implications, being associated with significant delays in oncologic treatments and extremely high mortality when contracted in the post-operative period.

"Clock mapping" prior to excisional surgery in vulvar Paget's disease: tailoring the surgical plan.

INTRODUCTION: Paget disease is a rare neoplasm of the skin that mainly involves the vulvar region. Vulvar Paget's disease (VPD) can spread beyond the apparent edges of the lesion resulting in a high risk of involved surgical margins. Our aim is to verify the efficacy of a preoperative vulvo-vaginal intensive clock mapping in the prediction of the invasiveness and the extension of VPD. MATERIALS AND METHODS: All consecutive patients with primary VPD referred to our institution from July 2005 to December 2018 were subjected to a preoperative intensive biopsy mapping (clock mapping) of the vulvo-vaginal area: inside and outside the vulvar skin visible lesion, according to o'clock positions, and in the vagina. Patients with positive biopsies "only inside" or "also beyond" the visible lesion were included, respectively, in Group A and B. Surgical excision was drawn passing by the points with negative histology. Pathological findings of mapping biopsies were compared with those from radical surgery. RESULTS: A total of 28 women were enrolled. After clock mapping definitive histology: 17 (60.7%) and 11 (39.3%) patients were included in Group A and B. Definitive histology showed non-invasive, micro-invasive and invasive VPD, respectively, in 13 (46.4%), 11 (39.3%) and 4 (14.3%) patients, with 4 patients further upstaged. Overall, negative margins were found in 14 (50%) patients: 9 (32.1%) from Group A and 5 (17.9%) from Group B. In 23 cases (82.1%), clock mapping identified free surgical margins along the vulvo-perineal skin excision front. CONCLUSIONS: Preoperative clock mapping emerged as potentially useful workup tool to predict invasiveness and extension of VPD, to tailor surgical excision.

Observational multicenter Italian study on vulvar cancer adjuvant radiotherapy (OLDLADY 1.2): a cooperation among AIRO Gyn, MITO and MaNGO groups.

BACKGROUND: Adjuvant radiotherapy (aRT) has been shown to reduce the risk of local relapse in vulvar cancer (VC). In this multicentre study (OLDLADY-1.2), several Institutions have combined their retrospective data on VC patients to produce a real-world dataset aimed at collecting data on efficacy and safety of aRT. METHODS: The primary study end-point was the 2-year-local control, secondary end-points were the 2-year-metastasis free-survival, the 2-year-overall survival and the rate and severity of acute and late toxicities. Participating centres were required to fill data sets including age, stage, tumor diameter, type of surgery, margin status, depth of invasion, histology, grading as well technical/dosimetric details of radiotherapy. Data about response, local and regional recurrence, acute and late toxicities, follow-up and outcome measures were also collected. RESULTS: One hundred eighty-one patients with invasive VC from 9 Institutions were retrospectively identified. The majority of patients were stage III (63%), grade 2 (62.4%) squamous carcinoma (97.2%). Positive nodes were observed in 117 patients (64.6%), moreover tumor diameter > 4 cm, positive/close margins and depth of invasion deeper than 5 mm were found in 59.1%, 38.6%, 58% of patients, respectively. Sixty-one patients (33.7%) received adjuvant chemoradiation, and 120 (66.3%) received radiotherapy alone. aRT was started 3 months after surgery in 50.8% of patients. Prescribed volumes and doses heterogeneity was recorded according to margin status and nodal disease. Overall, 42.5% locoregional recurrences were recorded. With a median follow-up of 27 months (range 1-179), the 2-year actuarial local control rate, metastasis free and overall survival were 68.7%, 84.5%, and 67.5%, respectively. In term of safety, aRT leads to a prevalence of acute skin toxicity with a low incidence of severe toxicities. CONCLUSIONS: In the context of aRT for VC the present study reports a broad spectrum of approaches which would deserve greater standardization in terms of doses, volumes and drugs used.

Treatment of Early-Stage Gynecological Cancer-Related Lower Limb Lymphedema by Lymphaticovenular Anastomosis-The Triple Incision Approach.

Background and Objectives: Lower extremity lymphedema (LEL) is one of the most relevant chronic and disabling sequelae after gynecological cancer therapy involving pelvic lymphadenectomy (PL). Supermicrosurgical lymphaticovenular anastomosis (LVA) is a safe and effective procedure to treat LEL, particularly indicated in early-stage cases when conservative therapies are insufficient to control the swelling. Usually, preoperative assessment of these patients shows patent and peristaltic lymphatic vessels that can be mapped throughout the limb to plan the sites of skin incision to perform LVA. The aim of this study is to report the efficacy of our approach based on planning LVA in three areas of the lower limb in improving early-stage gynecological cancer-related lymphedema (GCRL) secondary to PL. Materials and Methods: We retrospectively reviewed the data of patients who underwent LVA for the treatment of early-stage GCRL following PL. Patients who had undergone groin dissection were excluded. Our preoperative study based on indocyanine green lymphography (ICG-L) and color doppler ultrasound (CDU) planned three incision sites located in the groin, in the medial surface of the distal third of the thigh, and in the upper half of the leg, to perform LVA. The primary outcome measure was the variation of the mean circumference of the limb after surgery. The changes between preoperative and postoperative limbs' measures were analyzed by Student's t-test. p values < 0.05 were considered significant. Results: Thirty-three patients were included. In every patient, three incision sites were employed to perform LVA. A total of 119 LVA were established, with an average of 3.6 for each patient. The mean circumference of the operated limb showed a significant reduction after surgery, decreasing from 37 cm ± 4.1 cm to 36.1 cm ± 4.4 (p < 0.01). Conclusions: Our results suggest that in patients affected by early-stage GCRL secondary to PL, the placement of incision sites in all the anatomical subunits of the lower limb is one of the key factors in achieving good results after LVA.

New developments in rare vulvar and vaginal cancers.

PURPOSE OF REVIEW: To provide the latest insight on the rare vulvar and vaginal malignancies, able to impact on clinical practice, and to outline new potential research developments. RECENT FINDINGS: Many efforts are being made to produce technical and scientific advances in the fields of vulvar and vaginal carcinoma, including imaging work-up, interventional procedures and minimally invasive surgical approach, as well as molecular profiling and identification of new target treatments. SUMMARY: In the evaluation of lymph node status, ultrasound has demonstrated promising results because of high predictive value, low risk and low cost. Positron Emission Tomography-Computed Tomography is confirmed to be reliable and should be prospectively investigated for its potential applications in radiomics, whilst Fusion-US could allow a precision guidance in diagnostics and interventional procedures. Regarding interventional procedure, surgery is becoming less invasive with the aim to increase quality of life; in carefully selected patients it would be possible to overcome the current strict criteria in the use of sentinel node biopsy. Future research should focus on potential target therapy, on the basis of tumor-specific biological features.Rare cancers should be referred to experienced centers with a high case flow, able to offer a full range of diagnostic and therapeutical options and a multidisciplinary approach. Networking should be encouraged to promote research opportunities and enable data sharing and multicenter trials.

Diagnostic performance of preoperative [18F]FDG-PET/CT for lymph node staging in vulvar cancer: a large single-centre study.

PURPOSE: This retrospective study aimed to assess the diagnostic performance of preoperative [18F]FDG-PET/CT in predicting the groin and pelvic lymph node (LN) status in a large single-centre series of vulvar cancer patients. METHODS: Between January 2013 and October 2018, among all consecutive women with proven vulvar cancer submitted to [18F]FDG-PET/CT, 160 patients were included. LNs were analysed by two qualitative methods assessing PET information (defined as visual assessment) and a combination of PET and low-dose CT information (defined as overall assessment), respectively, as well as semi-quantitative analysis (LN-SUVmax). Sensitivity, specificity, accuracy, positive and negative predictive values (PPV and NPV) in predicting the groin and pelvic LN status were calculated in the overall study population; a subset analysis of groin parameters in clinically/ultrasonography negative patients was also performed. Histopathology was the reference standard. RESULTS: All patients underwent vulvar and inguinofemoral LN surgery, and 35 pelvic LN surgery. Overall, 338 LN sites (296 groins and 42 pelvic sites) were histologically examined with 30.4% prevalence of metastatic groins and 28.6% for metastatic pelvic sites. In the overall study population, sensitivity (95% confidence interval, CI), specificity (95% CI), accuracy (95% CI), PPV (95% CI) and NPV (95% CI) at the groin level were 85.6% (78.3-92.8), 65.5% (59.0-72.0), 71.6% (66.5-76.8), 52.0% (44.0-60.1) and 91.2% (86.7-95.8) for visual assessment; 78.9% (70.5-87.3), 78.2% (72.5-83.8), 78.4% (73.7-83.1), 61.2% (52.3-70.1) and 89.4% (85.0-93.9) for overall assessment; and 73.3% (64.2-82.5), 85.0% (80.1-89.8), 81.4% (77.0-85.8), 68.0% (58.8-77.3) and 87.9% (83.4-92.5) for semi-quantitative analysis (SUVmax cut-off value 1.89 achieved by ROC analysis). Similar results were observed in the pelvis-based analysis. CONCLUSION: In this large single-centre series of vulvar cancer patients, [18F]FDG-PET/CT showed good values of sensitivity and NPV in discriminating metastatic from non-metastatic LNs. In routine clinical practice, qualitative analysis is a reliable interpretative criterion making unnecessary commonly used semi-quantitative methods such as SUVmax.

Clinical and ultrasound characteristics of vaginal lesions.

OBJECTIVE: Ultrasound examination represents the most important diagnostic method to preoperatively assess gynecological diseases. However, the ultrasound characteristics of vaginal pathologies are poorly investigated. The aim of this study was to describe the clinical and ultrasound characteristics of vaginal lesions detected at ultrasound. METHODS: This was a single center, prospective, observational study including patients with vaginal masses examined from January 2017 to May 2019. Morphologic sonographic characteristics of the lesions were described as unilocular, multilocular, unilocular-solid, multilocular-solid, and solid. For the analysis, patients were grouped into a 'malignant group', including patients with confirmed malignancy at final histology, and a 'benign group', including patients with a confirmed benign pathology at final histology and patients without a histological diagnosis but with a lesion that manifested no changes during follow-up. RESULTS: 44 patients were enrolled. 22 (50%) of 44 lesions were benign: 12 (54.5%) of these underwent ultrasound follow-up and did not show any changes at the 12 month follow-up whereas 10 (45.5%) lesions had surgical excision which confirmed the benign nature. The remaining 22 (50%) of 44 lesions underwent surgery because of suspicion of malignancy: histology confirmed a malignancy in 20 (90.9%) of 22 cases. Benign lesions were described as follow: 11/24 (45.8%) unilocular, 3/24 (12.5%) multilocular with two locules, and 10/24 (41.7%) solid lesions. Malignant lesions were solid in 19/20 (95%) cases and multilocular-solid in 1/20 (5%). Most benign lesions had a color score of 1-2 (20/24, 83.4%) while malignant lesions had a color score of 3-4 (18/20, 90%). CONCLUSION: A typical ultrasound image of a benign lesion was a unilocular cyst or hypoechoic solid mass with no or minimal vascularization on color Doppler examination. Malignant vaginal lesions were hypoechoic solid tumors with irregular margins and moderate/rich vascularization or multilocular-solid. Ultrasound should be used to supplement the clinician in the management of vaginal lesions.

Lymphoscintigraphy and sentinel lymph node biopsy in vulvar carcinoma: update from a European expert panel.

PURPOSE: This study aimed to update the clinical practice applications and technical procedures of sentinel lymph node (SLN) biopsy in vulvar cancer from European experts. METHODS: A systematic data search using PubMed/MEDLINE database was performed up to May 29, 2019. Only original studies focused on SLN biopsy in vulvar cancer, published in the English language and with a minimum of nine patients were selected. RESULTS: Among 280 citations, 65 studies fulfilled the inclusion criteria. On the basis of the published evidences and consensus of European experts, this study provides an updated overview on clinical applications and technical procedures of SLN biopsy in vulvar cancer. CONCLUSIONS: SLN biopsy is nowadays the standard treatment for well-selected women with clinically negative lymph nodes. Negative SLN is associated with a low groin recurrence rate and a good 5-year disease-specific survival rate. SLN biopsy is the most cost-effective approach than lymphadenectomy in early-stage vulvar cancer. However, future trials should focus on the safe extension of the indication of SLN biopsy in vulvar cancer. Although radiotracers and optical agents are widely used in the clinical routine, there is an increasing interest for hybrid tracers like indocyanine-99mTc-nanocolloid. Finally, it is essential to standardise the acquisition protocol including SPECT/CT images, and due to the low incidence of this type of malignancy to centralise this procedure in experienced centres for personalised approach.

Palliative electrochemotherapy in primary or recurrent vulvar cancer.

OBJECTIVE: Since vulvar cancer is such a rare disease, the international experience with electrochemotherapy has been derived from only a few centers. The aim of this study was to evaluate clinical outcome and side effects profile with the use of electrochemotherapy in patients with primary or recurrent vulvar cancer. METHODS: Data were retrospectively collected from November 2017 to November 2019 in two major Italian oncologic institutes: Regina Elena Institute and Fondazione Policlinico Universitario Agostino Gemelli IRCCS. Electrochemotherapy was offered in a palliative setting to patients with a primary or recurrent vulvar cancer who were not candidates for surgery or any other treatment, because of poor performance status or previous delivered treatments. All patients underwent general anesthesia. Electrical pulses were delivered using a pulse generator. Intravenous bleomycin was administered in conjunction with electrochemotherapy. Follow-up examinations were performed at 1, 3, and 6 months. Primary endpoint was to assess the response rate of electrochemotherapy as palliative treatment in patients with vulvar cancer. RESULTS: A total of 15 patients were included in the study. Fourteen patients (93.3%) had a squamous cell carcinoma and one patient had vulvar carcinosarcoma. Ten patients (66.7 %) had a single lesion and 5 patients (33.3%) had multiple lesions. Median number of electrical pulses was 22 (range 3-42) and median operative time was 13 (range 7-20) min. No intra-procedure complications occurred. One patient had pneumonia during their post-operative stay. Overall response rate after 1 month was 80%. At the 3-month follow-up, 3 patients (20%) had disease progression, 3 patients (20%) had died from ongoing disease, 1 patient (6.7%) died for other reasons, whereas the other patients maintained their 1-month clinical response. A total of 8/13 patients (61.5%) were alive at 6-month follow-up, whereas 6/12 patients (50%) were alive at 1-year follow-up. CONCLUSIONS: Electrochemotherapy is a feasible, easy to perform, and reproducible procedure in patients with primary or recurrent vulvar cancer who are unable to undergo surgery. Survival after 1 year in this population was 50%. Electrochemotherapy may have a role in the management of vulvar cancer, especially as palliative treatment when other therapies are no longer applicable.

Multidisciplinary personalized approach in the management of vulvar cancer - the Vul.Can Team experience.

INTRODUCTION: Multidisciplinary treatment strategy involving adjuvant radiotherapy for advanced vulvar cancer could be useful in offering the best personalized clinical approach. In 2013, the VULvar CANcer Multi-Disciplinary Team (Vul.Can MDT) was set up in our institution, in order to share knowledge and expertise, high-quality diagnosis, and evidence-based decision making in the context of personalized medicine. The aim of this observational study was to report on our series of vulvar cancer patients managed postoperatively with radiotherapy within the framework of a formal multidisciplinary tumor board. METHODS: Coupling surgical and oncological international guidelines with "case-by-case" discussions, a multi-specialist consensus was progressively reached and internal recommendations were developed and introduced in the daily routine. Data from vulvar cancer patients who underwent primary surgery and adjuvant radiotherapy throughout a 5-year period were retrospectively collected. Actuarial local control was the primary endpoint, while secondary end-points were acute and late toxicities, disease-free survival, and overall survival. Toxicity was evaluated according to the Common Toxicity Criteria Adverse Event v 4.0 scale. RESULTS: The analysis included 35 patients with squamous vulvar cancer treated with adjuvant radiotherapy±chemotherapy, from April 2013 to September 2017. Median age was 70 years (range 18-87), all patients underwent surgery followed by concomitant chemoradiation (45.7%) or radiotherapy alone (54.3%). The median prophylactic dose on lymphatic drainage was 45 Gy, while positive nodes and perineal area received 51.2 Gy and 52.6 Gy, respectively. Chemotherapy involved the cisplatin-based regimen (45.7%)±5-fluorouracil (37.1%). Median follow-up was 32 months (range 6-72): the 24-months local control, disease-free survival, and actuarial overall survival rates were 88.6%, 82.0%, and 91.0%, respectively. Low rates of severe acute (12%) and late (3%) toxicities occurred. DISCUSSION: The outcomes of this series support the benefit of a multidisciplinary personalized approach in the management of vulvar cancer.

Nipple-sparing mastectomy combined with endoscopic immediate reconstruction via axillary incision for breast cancer: A preliminary experience of an innovative technique.

INTRODUCTION: Nipple-sparing mastectomy (NSM) has known an exponential diffusion worldwide for prophilaxis and therapeutic mastectomies in selected candidates, being oncologically safe and improving reconstructive outcomes and patients' satisfaction. The two most common used skin incisions are the radial and inframammary fold ones, which represent an imperfect aesthetic solution. The aim of this work was to give insights on our surgical technique, which allows to perform the NSM, node surgery, and endoscopic direct-to-implant reconstruction using a cosmetic axillary incision. MATERIALS AND METHODS: Between June 2016 and January 2019, 7 consecutive patients underwent NSM, lymph node surgery and endoscopic direct-to-implant reconstruction using a small cosmetic axillary incision for breast cancer treatment in a single Institution. An operative rigid endoscope with working channel (Richard Wolf) was used to dissect the entire submuscular-subfascial pocket. The mean age of the patients was 42.8 years old (range: 36-49 years). The evaluation methods were clinical and photography-based assessments, as well as the BREAST-Q which was used to quantify patient satisfaction. RESULTS: The average follow-up time was 9 months (range 3-22 months). Tumor-free margins were obtained in all cases. No tumor recurrence or metastasis occurred during follow-up. No major complications were experienced. There were no cases of malposition, wrinkling, or rippling. All patients were satisfied with their esthetic results, especially the absence of visible scars. CONCLUSIONS: From our preliminary experience, NSM combined with endoscopic immediate reconstruction via axillary incision for breast cancer treatment seems to be a promising new procedure in cup A and B breasts alternative to the conventional techniques, as it allowed to have safe and pleasant aesthetic and oncologic outcomes.

Transaxillary Nipple-Sparing Mastectomy and Direct-to-Implant Breast Reconstruction Using a Simplified Endoscopic Approach: Indications, Cosmetic Outcomes and Technical Refinements.

BACKGROUND: The increasing demand for further aesthetic outcome improvement in implant-based breast reconstruction after nipple-sparing mastectomy (NSM) leads to major novelties, including endoscopic and robotic NSM with the aim to limit scar visibility. In this paper, we report our experience with a novel and simplified surgical approach-single-axillary-incision non-endoscopic NSM and node surgery followed by an endoscopic DTI breast reconstruction-by focusing on reconstructive indications, technical refinements and aesthetic outcomes. METHODS: Between June 2016 and October 2019, 14 women underwent this novel technique using definitive anatomical silicone gel filled, totaling 20 breasts. Reconstructive evaluation methods were clinically and photography-based assessment. Breast-Q has been used to quantify patient satisfaction. Feasibility and safety data are also provided. RESULTS: The average follow-up time was 11 months (range 3-42 months). No local-regional recurrence occurred during follow-up. Median operation time was 340 min; mean hospital stay was 4.1 days. The average mastectomy specimen weight was on average 139 g (ranging from 98 to 182 g). The average implant volume for the reconstructed side was 306 cc (ranging from 165 to 550 cc). Patients' satisfaction was high to very high. CONCLUSION: Authors' experience suggests that non-endoscopic transaxillary NSM, node surgery and endoscopic direct-to-implant breast reconstruction is a valid, oncological safe, aesthetically sound scarless option in breast cancer patients with small to moderate breast size. It should represent the incision of choice in patient with previous breast surgery with scars that may compromise flap/NAC vascularity using traditional NSM incisions. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Reviewing vulvar Paget's disease molecular bases. Looking forward to personalized target therapies: a matter of CHANGE.

OBJECTIVES: To review the published literature on vulvar Paget's disease (VPD) molecular bases, aiming to support the need for tailored treatment in women affected by this 'orphan' tumor. METHODS: MEDLINE-PubMed and Scopus were interrogated using the following algorithm: (extramammary OR extra mammary OR vulvar) AND (paget OR pagets OR paget's) AND (molecular OR biological OR marker OR protein OR target OR expression). The inclusion criteria for papers were: peer-reviewed English-language journals, articles published in the last 30 years, studies focused on fixed research questions, quality assessment on the basis of the relevance and contribution to the selected topics. RESULTS: A total of 42 studies were selected, providing the following results. Molecular markers implicated in cell cycle transitions seem to be related to prognosis and could help to tailor conventional treatments. Fragmented but consistent preliminary data exist on hormonal receptor expression, ERBB2 amplification/overexpression and abnormal vascular proliferation, offering a concrete possibility for target therapy trials. Conversely, other fields linked to the possible use of immunotherapy are currently relatively unexplored, such as the tumor 'immune contexture', programmed death ligand-1 (PD-L1) expression and defects in the mismatch repair system, which is involved in genomic instability and potentially promotes a consistent response to treatment. CONCLUSIONS: Additional effort is needed to further characterize these aspects. Centralization of patients in dedicated units would be beneficial for concentrating patient numbers, collecting valuable clinical data and conducting clinical trials. Interdisciplinary study platforms should be developed and integrated into wider multicentric networks.