Pelvic Node Involvement Research Articles

Lateral pelvic lymph node positivity (LPLNP) score: predictive clinic-radiological model of lateral pelvic lymph node involvement in rectal cancer patients

PurposeThe population in Western countries differs significantly from that in Eastern countries, and the prevalence of lateral pelvic lymph node (LPLN) involvement in Western populations remains largely unknown due to the limited application of LPLN dissection (LPLND). This discrepancy is primarily attributed to the higher body mass index commonly observed in Western populations, which increases the risk of intraoperative complications. Consequently, the aim of this study is to describe a specific Western clinico-radiological selection tool for LPLND, namely, the lateral pelvic lymph node positivity (LPLNP) score.MethodsThis retrospective single center study was designed to elaborate the LPLNP score, which was further tested on a prospective cohort of patients. Clinical and MRI factors associated with LPLN involvement were identified, and logistic regression was used to establish the LPLNP score.ResultsIn the retrospective series, 120 patients underwent lateral pelvic lymph node dissection. After stepwise logistic regression, five parameters were ultimately included in the LPLNP score. When tested on 66 prospectively selected patients, 40 with an LPLNP score > 0.23 (corresponding to the highest sensitivity and specificity) underwent LPLND: 22 patients (55%) had pathologically confirmed positive LPLN. The negative predictive value of the LPLNP score was 96%, with a sensitivity of 95.7% and a specificity of 58.1%.ConclusionThe LPLNP score was developed based on the largest group of Western patients with locally advanced rectal cancer. This scoring system demonstrated high sensitivity and specificity during validation on the prospective series, correctly identifying LPLN involvement in 55% of cases.

Three-Dimensional Conformal Radiotherapy Versus Image-Guided Intensity Modulated External Beam Radiotherapy in Locally Advanced Cervical Cancer: A Phase III Randomized Control Study

AimsThe standard treatment of locally advanced cervical carcinoma is radical chemoradiation followed by brachytherapy which has improved survival. Hence, a major concern is our attempt to reduce the incidence of acute and late toxicities. IMRT has been shown to reduce toxicities. In this study, we have compared 3DCRT with IG-IMRT using patient-specific margins to evaluate tumor control as well as OAR-related toxicities. Materials and MethodsThis was a single institution prospective phase III randomised control study including patients of squamous cell carcinoma of cervix (stage II–IIIB, FIGO 2009) without pelvic lymph node involvement. All patients were simulated using intermediate bladder filling protocol and those in the IG-IMRT arm, underwent additional scans with full and empty bladder to assess the range of internal motion and generate individualised ITV margin. EBRT dose of 46Gy/23#/4.5 weeks was delivered with weekly concurrent cisplatin followed by brachytherapy. All toxicities during EBRT and till 3 months post brachytherapy were considered acute toxicity. Post-treatment, patients were followed up every 2 months for first 2 years and then once every 6 months. Disease-related outcomes were assessed with clinical examination and symptom-directed imaging. ResultsTwo hundred patients were screened for inclusion and of them, 89 patients in 3DCRT and 84 patients in IG-IMRT arms were considered for final analysis. The baseline characteristics were comparable in both arms, majority of patients in both arms having stage II disease. For OARs, all dosimetric parameters were significantly better in the IG-IMRT arm. Acute radiation induced toxicities (dermatitis, genito-urinary and gastrointestinal toxicities) were significantly less in the IG-IMRT arm. The local, pelvic, and distant control were comparable in both arms. ConclusionBased on our experience, the use of IG-IMRT with patient-specific ITV margins results in reduction in acute OAR toxicities in patients without compromising on tumor control.

Single centre real world data on disease profile and outcome of 700 patients with penile cancer treated with curative intent at an Indian cancer centre.

121 Background: Globocan 2022 reported that there are close to 10000 newly diagnosed penile cancer (PeCa) patients annually in India, which contributes to around 27% of the world’s burden of this disease. With the rarity of this male genitourinary cancer globally and absence of level I evidence on most aspects of the disease, real world data from a single Centre assumes importance and this retrospective study highlights the clinico-demographic profile, oncological outcome and surgical complications in patients treated with a curative intent. Methods: We retrospectively reviewed our prospectively maintained institutional database for patients with PeCa treated with curative intent from 2013 to 2021. Data was collected for demographic variables, clinico-pathological characteristics, post-operative complications and oncological outcomes. Descriptive data were expressed as mean / median / proportions. The Kaplan Meier method was used to calculate the cancer specific survival (CSS) of the patients, stratified by pN status. Results: From 2013 to 2021, 700 patients were treated for PeCa at our centre with curative intent, with a median age of 54 years (IQR 44-62) and a mean BMI of 24.1 kg/m2. Around 40% of the patients had history of tobacco use. The clinico-pathological features and Clavian Dindo complication rates are summarized in the table. With a median follow-up of 42 months, the CSS for cN0 patients under observation for their groins was 97.3%.CSS for patients with pN0, pN1, pN2 and pN3 was 90.6%, 79.4%, 71.4% and 55%. Amongst pN3, 24.3% received adjuvant chemo alone, 23.7% received adjuvant RT/CTRT alone while 33.7% received both adjuvant chemo and RT.CSS of pelvic nodal pN3 patients was 35% compared to 71% of inguinal perinodal extension pN3. Conclusions: Our series, one of the largest reported from a single centre, highlights the real world oncological outcome of PeCa patients. We reemphasize the importance of addressing inguinal nodes early and adequately and the worser outcome of pN3 due to pelvic node involvement compared to pN3 due to extra nodal extension of inguinal nodes. [Table: see text]

Staging of Cervical Cancer: What has Changed?

In India, cervical cancer is the second most common cause of cancer-related fatalities and the fourth most common malignancy worldwide affecting women. India accounts for 25% of all cervical cancer-related deaths worldwide each year. The main drawbacks of clinical staging were the imprecise estimation of tumor size and the challenge of determining the involvement of pelvic and para-aortic lymph nodes with the few studies that FIGO allowed to be done for staging of cancer cervix. The use of 2009 staging approach showed that when many cases were operated based only on clinical findings, they subsequently required adjuvant therapy; hence, treatment-related morbidity was negatively impacted by these errors. Changes have been made to the staging of cervical cancer according to the 2018 revised International Federation of Gynecology and Obstetrics (FIGO) guidelines. Correction to cancer of the cervix staging was published recently in 2024. The horizontal extent (lateral extent) of the disease is not taken into consideration for staging in cases of microinvasive disease. Three subgroups have been identified based on the stratification of tumor size: IB1 ≤ 2cm, IB2 > 2- ≤ 4cm, and IB3 > 4cm. Pathology and imaging modalities are added to clinical diagnosis for staging of cancer cervix. The involvement of lymph nodes (LNs) is now classified based on pathology (p) or imaging (r) which specifies that lymph node involvement is diagnosed using pathology (p) or imaging (r). Stage IIIC has been added [IIIC1 (involvement of pelvic nodes) and IIIC2 (involvement of para-aortic nodes)] is assigned to the case in the event of lymph node positive status. Pathological assessment takes precedence over radiological and clinical findings. The involvement of vascular/lymphatic spaces should not change the staging. The lower staging should be assigned when there is doubt about stage. Overall, the revised FIGO staging of cancer cervix (2024) has a number of advantages, including the inclusion of imaging and pathology, tumor size and LN-based categorization. More studies on staging of cancer cervix in different populations using revised staging of cancer cervix will help to prognosticate use of this staging.

Prognostic Importance of 18F-FDG Positron Emission Tomography in Uterine Cervical Cancer.

The aim of this study was to evaluate the prognostic value of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in the uterine cervix cancer patients. Thirty-two women (mean age: 52.7±12.6) who underwent 18F-FDG PET/CT for staging of uterine cervix cancer were retrospectively recruited for the study. Maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for primary tumors, lymph nodes, and distant metastases were calculated from 18F-FDG PET/CT images using the 40% threshold. Patients were divided into groups according to the presence of pelvic and para-aortic lymph node involvement on 18F-FDG PET/CT images. Life tables and Kaplan-Meier analyses were performed to compare the mean survival times of the different groups. Primary tumor of 27 (84%) patients were 18F-FDG avid. The median SUVmax, SUVmean, MTV, and TLG of the primary tumors were 12.4, 6.1, 13.2 cm3 and 87.8 g/mL x cm3 respectively. Pathological uptake was detected in pelvic 14 (44%) patients and in paraaortic lymph nodes in 3 (10%) para-aortic lymph nodes. The median whole-body MTV and TLG were 21.7 cm3 and 91.1 g/mL x cm3. Disease progression was detected in 7 (22%) patients within a median follow-up period of 20.9 (minimum-maximum: 3-82) months. The only significant PET parameter to predict progression-free survival was SUVmax in the primary tumor (p=0.038). During follow-up period 8 patients died. SUVmax (p=0.007), MTV (p=0.036), TLG (p=0.001) of primary tumor, presence of pathological uptake on pelvic or paraaortic lymph nodes (p=0.015), whole-body MTV (p=0.047) and whole-body TLG (p=0.001) were found statistically significant PET parameters to predict overall survival. Metabolic parameters of primary tumors derived from 18F-FDG PET/CT images have prognostic importance for patients with uterine cervical carcinoma. In patients with metastatic disease, higher whole-body MTV and TLG are also associated with poor prognosis.

Clinical Outcomes and Treatment Efficacy in Cervical Cancer Patients in the UAE: A Retrospective Cohort Study.

Background and objectives Cervical cancer remains a significant global health issue, particularly in low- and middle-income countries. While high-income countries have seen reduced incidence and mortality rates due to effective screening and HPV vaccination programs, these rates are still high in areas with limited healthcare infrastructure. In the United Arab Emirates (UAE), recent efforts are improving public health initiatives and awareness. This retrospective cohort study evaluates clinical outcomes and treatment efficacy in cervical cancer patients at a tertiary cancer center in Al Ain, Abu Dhabi. It analyzes treatment regimens, their effectiveness, and factors affecting survival, disease progression, and treatment completion. Methods and material The study included 275 cervical cancer patients treated between January 2008 and December 2021. Data were extracted from medical records, including demographic information, clinical characteristics, and treatment details. Statistical analyses, including Kaplan-Meier survival curves and Cramér's V correlation matrix, were used to evaluate survival outcomes and the relationships between various categorical variables. Results The mean age of patients was 48.88 years, with the majority being non-nationals, 221 (80.37%). Histopathologically, there were 234 (85.18%) cases of squamous cell carcinoma (SCC) and 33 (11.85%) cases of adenocarcinomas. The International Federation of Gynecology and Obstetrics (FIGO) staging indicated that 137 (49.80%) patients were in stage II and 60 (21.81%) were in stage III. Pelvic lymph node involvement was observed in 139 (50.54%) patients. The treatment modalities included surgery in 39 (14.18%) patients, 3D conformal radiotherapy (3D-CRT) in 247 (89.81%) patients, intensity-modulated radiation therapy (IMRT) in 11 (4.00%) patients, brachytherapy in 213 (77.45%) patients, and chemotherapy in 248 (90.18%) patients. The survival analysis showed no significant differences in survival among different treatment groups, as indicated by the Log-rank test (p = 0.4060). Conclusion The study highlights the demographic and clinical characteristics of cervical cancer patients in the UAE, emphasizing the prevalence of advanced-stage diagnoses and high-grade tumors. Despite significant efforts to improve screening and treatment, cervical cancer remains a concern in the UAE. The findings underscore the need for enhanced early detection and comprehensive treatment strategies. Addressing the study's limitations, such as the retrospective design and the absence of human papillomavirus (HPV) data, could further refine cervical cancer management and improve patient outcomes in future research.

Pelvic lymph node involvement and risk of recurrence in HPV-associated endocervical adenocarcinoma stage IA2-IB1 according to Silva's system in two Colombian cancer centers.

To compare the pelvic lymph node involvement and risk of recurrence in patients with human papillomavirus (HPV)-associated endocervical adenocarcinoma stage IA2-IB1 undergoing hysterectomy and/or trachelectomy plus lymphadenectomy, according to Silva's classification system. A retrospective cohort study was performed in two Colombian cancer centers. The cases were classified according to the Silva classification system. Clinical, surgical, and histopathological variables were evaluated. Recurrence risk was analyzed by patterns A, B, or C. A logistic regression model was performed for tumor recurrence. The Kaplan-Meier method was used to estimate overall survival and disease-free survival (DFS). A weighted kappa was performed to determine the degree of concordance between pathologists. A total of 100 patients were identified, 33% pattern A, 29% pattern B, and 38% pattern C. The median follow-up time was 42.5 months. No evidence of lymph node involvement was found in patients classified as A and B, while in the C pattern was observed in 15.8% (n = 6) of cases (P < 0.01). There were 7% of cases with recurrent disease, of which 71.5% corresponded to type C pattern. Patients with Silva pattern B and C had 1.22- and 4.46-fold increased risk of relapse, respectively, compared with pattern A. The 5-year DFS values by group were 100%, 96.1%, and 80.3% for patterns A, B, and C, respectively. For patients with early-stage HPV-associated endocervical adenocarcinoma, the type C pattern presented more lymph node involvement and risk of recurrence compared to the A and B patterns. The concordance in diagnosis of different Silva's patterns by independents pathologists were good.

Intraepithelial tumor-infiltrating lymphocytes shape loco-regional PET/CT spread of locally advanced cervical cancer

BackgroundData suggest an association between positron emission tomography/CT (PET/CT) metabolic metrics and tumor microenvironment in several malignancies, and a potential role of PET/CT to monitor response to immunotherapy.ObjectiveTo evaluate the...

Longitudinal circulating tumor DNA monitoring for detection of molecular residual disease in patients with penile squamous cell carcinoma.

11 Background: Penile squamous cell carcinoma (SCC) is an extremely rare, aggressive disease, representing 0.4-0.6% of all malignancies in males in the U.S. and Europe. Early diagnosis is imperative, as lymphatic spread is associated with a dismal prognosis. The estimated 5-year survival rate in patients with pelvic lymph node involvement is 0%. Moreover, there are limited treatment options that carry significant toxicity risks. Accurate biomarkers to evaluate treatment response and guide treatment to improve outcomes are needed. Molecular residual disease monitoring with circulating tumor DNA (ctDNA) may be helpful in these scenarios. Methods: This is a retrospective analysis of a cohort of 7 patients with advanced HPV-unassociated penile SCC treated at Rush University Medical Center who monitored closely for molecular residual disease (MRD). Signatera (Natera Inc.), a personalized tumor-informed ctDNA assay, was utilized for detection and quantification of ctDNA in patients’ plasma samples, measured at regular intervals. Progression of disease was based on radiographic imaging. Results: In our cohort, personalized, tumor-informed ctDNA assays were designed for 100% (7/7) of the patients. ctDNA was detectable in at least one time point in all of the patients. One patient underwent partial penectomy and lymph node (LN) dissection with 1/11 LN involved. He is being monitored without adjuvant treatment and has sustained ctDNA clearance. Another patient underwent surgery, and had positive post-operative ctDNA. He was treated with adjuvant TIP (paclitaxel, ifosfamide, and cisplatin) with subsequent ctDNA clearance. In 3 of the patients, ctDNA was checked at regular intervals and rising ctDNA prompted imaging studies that showed progression. These patients proceeded to second line treatment options. The remaining 2 patients are non-surgical candidate with LN positivity, who will begin treatment with TIP and monitoring of ctDNA after each cycle of chemotherapy. Twenty-eight percent (2/7) of patients remain alive with sustained ctDNA clearance. Twenty-eight percent (2/7) of patients remain alive with ctDNA positivity, planned to initiate treatment and monitoring of ctDNA at regular intervals. Forty-three percent (3/7) of patients who had persistent ctDNA positivity are now deceased. Conclusions: Our data suggests that a personalized, tumor-informed ctDNA assay is not only useful for MRD monitoring, but also highly predictive of treatment response and imaging-based progression in patients with penile SCC. In our sample, MRD status correlated with both radiographic progression and clinical outcomes. Prospective studies are needed to better understand how ctDNA can be used to guide neoadjuvant and adjuvant approaches, including treatment intensification or de-escalation, in patients with penile SCC.

Utility of fluoro-deoxy-glucose positron emission tomography (FDG-PET) to predict a pelvic lymph node involvement (LNI) in patients (pts) with muscle-invasive bladder cancer (MIBC) enrolled in neoadjuvant therapy trials.

527 Background: FDG-PET is reported to have limited utility in pts with MIBC. However, standard computed tomography (CT) imaging can often underestimate disease extent, and its role in predicting a pathological pelvic lymph node involvement (LNI) is very limited. Previous findings from PURE-01 trial reported a potential use of FDG-PET to exclude the few pts with T2-4N0M0 and pelvic LN uptake from neoadjuvant trials with immune-checkpoint inhibitors (ICI; PMID: 33071107). The aim of this study was to extend these findings to a wider range of experimental therapies. Methods: We collected the data of pts with clinical stage T2-4N0-1M0 MIBC included in past and ongoing neoadjuvant trials sponsored by our center, including single agent or combination of immune-checkpoint inhibitors (ICI), ICI+chemotherapy (ChT), standard ChT and sacituzumab govitecan. All pts had predominant urothelial carcinoma (UC) histology and were staged with standard thorax-abdomen CT scan and with PET/CT scan during screening and after treatment, before radical cystectomy (RC). PET/CT images were evaluated qualitatively for increased or abnormal areas of FDG uptake with corresponding anatomic alterations in CT slices. All pts underwent templated pelvic lymph node dissection (LND) with packeted node submission. Multivariable logistic regression analyses (MVA) for pathological LNI prediction were run, including cT-stage and the presence of variant histologies (VH). Results: A total of 149 pts (298 PET scans) were identified, treated between 02/2017 and 08/2023. 112 pts (75.2%) received ICI, 26 (17.4%) ICI+ChT, 11 (7.4%) the remaining therapies. 36 pts (24%) had a VH, 72 (48%) a cT3-4 stage, and 12 (8.1%) a cN1 stage. In total, 20 (13%) and 16 (11%) pts had PET+ pre- and post-therapy, respectively. The accuracy of FDG-PET and CT scan in predicting LNI in overall pts was similar, both pre-therapy (85.3% and 86.7%) and post therapy (86.7%, 84.6%), the only exceptions being a lower accuracy of PET to predict presacral LNI (76.6%, 78.8% pre- and post-therapy) and in VH pre-therapy (84.3% vs 90.9% PET vs CT). A pre-therapy FDG uptake significantly predicted a pathological LNI in MVA (OR: 17.8, 95%CI: 4.18-94.86, p&lt;0.001, AUC: 0.89), with consistent results in T2-4N0M0 cohort (OR: 18.17, 95%CI: 4.15-99.25, p&lt;0.001, AUC: 0.84). Conclusions: Despite the proportion of FDG-PET positive pts was modest in T2-4N0-1M0 MIBC, we were able to confirm that these pts were predicted to be poor responders to neoadjuvant therapies regardless of the type of treatment. FDG-PET had lower prediction ability of LNI in presacral LN region and in pts with a VH. This information should be critically considered for patient selection in neoadjuvant therapy trials.

PSMA-Targeted Radiopharmaceuticals for Prostate Cancer Diagnosis and Therapy.

Prostate cancer (PCa) is the most common noncutaneous malignancy in men. Until recent years, accurate imaging of men with newly diagnosed PCa, or recurrent or low-volume metastatic disease, was limited. Further, therapeutic options for men with advanced, metastatic, castration-resistant disease were increasingly limited as a result of increasing numbers of systemic therapies being combined in the upfront metastatic setting. The advent of urea-based, small-molecule inhibitors of prostate-specific membrane antigen (PSMA) has partially addressed those shortcomings in diagnosis and therapy of PCa. On the diagnostic side, there are multiple pivotal phase III trials with several different agents having demonstrated utility in the initial staging setting, with generally modest sensitivity but very high specificity for determining otherwise-occult pelvic nodal involvement. That latter statistic drives the utility of the scan by allowing imaging interpreters to read with very high sensitivity while maintaining a robust specificity. Other pivotal phase III trials have demonstrated high detection efficiency in patients with biochemical failure, with high positive predictive value at the lesion level, opening up possible new avenues of therapy such as metastasis-directed therapy. Beyond the diagnostic aspects of PSMA-targeted radiotracers, the same urea-based chemical scaffolds can be altered to deliver therapeutic isotopes to PCa cells that express PSMA. To date, one such agent, when combined with best standard-of-care therapy, has demonstrated an ability to improve overall survival, progression-free survival, and freedom from skeletal events relative to best standard-of-care therapy alone in men with metastatic, castration-resistant PCa who are post chemotherapy. Within the current milieu, there are a number of important future directions including the use of artificial intelligence to better leverage diagnostic findings, further medicinal chemistry refinements to the urea-based structure that may allow improved tumor targeting and decreased toxicities, and the incorporation of new radionuclides that may better balance efficacy with toxicities than those nuclides that are available.

Predictive Role of Preoperative Whole-Body 18F-FDG PET/CT for Risk Stratification of Early-Stage (FIGO I-IIA) Cervical Cancer Patients Treated by Surgery.

The aim of the present study was to investigate the predictive value of maximum standardized uptake value (SUVmax) measured on preoperative 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in International Federation of Gynecology and Obstetrics (FIGO 2009) stage I-IIA cervical cancer patients who were treated with radical hysterectomy. A total of 47 patients with FIGO stage I-IIA cervical cancer who were evaluated preoperatively with biopsy and 18F-FDG PET/CT followed by radical hysterectomy were included in the study. Correlation between SUVmax and pathological risk factors or survival was studied. The mean SUVmax was significantly higher in patients with large tumor size (≥4 cm), advanced stage (IIA>IB>IA) and depth of invasion >50%. No significant difference was noted in SUVmaxbetween patients with and without pelvic lymph node involvement (P=0.639). SUVmax of the primary tumor with and without lymph-vascular invasion were 12.95 and 10.35, respectively (P=0.5). No significant difference was noted between patients with high SUVmax and low SUVmax with regards to overall survival (OS) and disease-free survival (DFS), using an optimal cut-off value of 7.65 for OS and DFS obtained from receiver operating characteristic (ROC) curve analysis. Patient with tumor size >4cm had 5.9 times more probability of mortality compared to tumor size <4cm (P=0.09). The present study observations showed that although SUVmaxis associated with pathological variables, it does not independently predict oncological outcomes in FIGO stage IA-IIA cervical cancer patients who were treated with radical hysterectomy. These findings suggest that SUVmax of primary tumor may be used for risk stratification, but not for prognostication insurgically treated early-stage cervical cancer patients. Not using other parameters of 18F-FDG PET/CT like metabolic tumor volume (MTV), tumor lysis glycolysis (TLG), small sample size,variation in calculation of SUVmax, histopathologic heterogeneity, inclusion of stage IA patients in the study were constraints of present study. Furtherstudies with large sample size using multi metabolic parameters of 18F-FDG PET/CT, including the SUVmax,SUVmean,SUVpeak, MTV and TLG are needed.

Predicting the Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer Using Soluble Immune Checkpoints.

Introduction: Personalizing neoadjuvant therapy for locally advanced rectal cancer (LARC) requires identifying biomarkers that predict treatment response. This study aims to evaluate soluble immune checkpoints (sICPs) as predictive markers for neoadjuvant treatment response in LARC patients located in the middle and lower rectum. Materials and Methods: This prospective study included patients diagnosed with clinical stage T3 or T4 rectal cancer (RC) based on pelvic magnetic resonance imaging, with or without pelvic lymph node involvement. The modified Ryan scoring system was used to assess the response to neoadjuvant chemoradiotherapy (nCRT). Blood samples were collected from all RC patients before initiating nCRT. Various sICPs (sCD25, 4-1BB, B7.2, free active TGF-β1, CTLA-4, PD-L1, PD-1, Tim-3, LAG-3, galectin-9), along with age, gender, stage, blood cell counts, and biochemical variables, were recorded and compared based on tumor regression grade (TRG). Results: Among 38 participants, lymphocyte count was higher, and platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and platelet count were lower in patients with complete/near-complete response (TRG 0/1). In addition, TRG 0/1 patients had significantly lower levels of soluble galectin-9 than TRG 2/3 patients. Furthermore, platelet count was the only parameter that showed a significant difference among the three groups (TRG 0/1, TRG 2, and TRG 3). PLR demonstrated the highest sensitivity and specificity, with >80% for both measures. Conclusions: Lymphocyte count, PLR, NLR, platelet count, and galectin-9 may help predict favorable neoadjuvant treatment response in LARC patients, although without providing a definitive outcome. Personalized therapy based on these markers could enhance treatment decision making in LARC management.

Prevalence and Pattern of Nodal Metastases in Ovarian Malignancy: A Perioperative Audit

It is still unclear whether or not full nodal dissection and detailed staging offer any benefits. Little is known regarding the degree of nodal involvement based on histotype. We aimed to assess the lymphatic dissemination patterns and prevalence in early-stage epithelial ovarian cancer and identify the underlying risk factors for nodal metastases. This is a prospective study conducted over a period of three years. Institutional ethics committee approval has been obtained. A total of 157 consecutive patients with apparently early-stage ovarian cancer, who were treated at the Department of Gynecologic Oncology, Acharya Harihar Post Graduate Institute of Cancer (AHPGIC) from January 2020 to January 2023, were included. The most frequent grade was 3 (66.8%), and the most common histotype was high-grade serous ovarian cancer (HGSOC; 55.4%), followed by mucinous (16.5%) and endometrioid (14.01%) varieties. Seromucinous and clear cell ovarian cancers were found infrequently. The most common pattern was isolated pelvic nodal involvement in 48.9% of patients, followed by both para-aortic and pelvic nodal involvement in 25.5% of patients; 13 patients had isolated para-aortic nodal involvement. HGSOC was most commonly associated with isolated metastasis to the pelvic lymph nodes alone, while the endometrioid variety was prone to both pelvic and para-aortic spread. Out of the 55 patients with nonserous tumors, 12.72% exhibited nodal involvement. Most nonserous tumors showed affinity for both pelvic and para-aortic (42.85%) nodal metastases. Only grade 3 and serous histology showed a positive association with nodal metastasis. Approximately 45.2% of cases showed upstaging after surgical staging procedures. Multicentric studies are essential to analyze the prognostic impact of systematic lymphadenectomy in ovarian carcinoma patients, depending on the histotype and distribution pattern of nodal metastases.

Machine Learning and Explainable Artificial Intelligence to Predict Occult Pelvic Nodal Metastases in Prostate Cancer.

Determination of risk of occult pelvic lymph node involvement (LNI) in patients with cN0 prostate cancer is critical for determination of optimal treatment options. Though several nomograms exist, machine learning (ML) approaches might enable physicians to better assess individual risk by incorporating multiple clinical risk factors. Herein, we developed a ML model to predict occult LNI, and explained its composition using an explainable artificial intelligence (XAI) framework. Patients with cN0 prostate adenocarcinoma diagnosed from 2018-2020 were identified in the National Cancer Database. The query was limited to patients with known clinical staging and biopsy results who did not receive neoadjuvant therapy prior to pelvic nodal examination. Occult LNI was defined as pN1 disease based on surgical evaluation, with a minimum of 10 nodes examined. Five ML models were trained to predict LNI. Variables incorporated into the model were age, core biopsy results, Gleason scores, preoperative prostate specific antigen (PSA), and clinical T-stage. Model performance, measured using area under the receiver operator characteristic curve (AUC) on a holdout testing dataset, was compared to multivariable logistic regression. The best-performing model was explained using SHapley Additive exPlanation (SHAP) values. To permit more clinically-meaningful statistical interpretation, using a novel approach SHAP values were converted into odds ratios (OR), confidence intervals (CI), and p-values. A total of 23,131 patients met inclusion criteria; 2,676 (11.6%) had occult LNI. The Extreme Gradient Boosting model outperformed all other models with an AUC of 0.82 (95% CI: 0.78-0.86) compared to 0.80 (95% CI: 0.76-0.84) for logistic regression. Increasing PSA (OR: 1.031; p<0.001), number of positive biopsy cores (OR: 1.055; p<0.001), and percent positive biopsy cores (OR: 1.01; p<0.001) were all associated with increased risk of LNI. Based on observation of SHAP dependence plots, risk of LNI plateaued at PSA>20 ng/dL and >11 positive cores, while no plateau was observed for percent positive biopsy cores. Relative to T1c disease, patients with T3b were at highest risk of LNI (OR: 1.461; p = 0.003). Gleason score of 9 was associated with significant risk of LNI (Ref: Gleason 6; OR: 1.891; p<0.001). This was primarily driven by the primary Gleason score; primary Gleason 5 disease was associated with significant risk of LNI (Ref: Gleason 3; OR: 1.915; p<0.001) while a secondary Gleason score of 5 was the only grade with significant increased risk of LNI (Ref: Gleason 3; OR: 1.185; p = 0.004). Age and number of cores examined were not significant predictors of LNI. Our ML achieved improved performance relative to logistic regression at predicting occult LNI. XAI provided insight into the inner-working of the ML model. ML can be used to identify patients at risk for occult LNI and therefore inform clinical decision-making.

Lymph node size detected by magnetic resonance imaging for prediction of lymph node involvement in locally advanced cervical cancer.

To investigate lymph node (LN) size detected by Magnetic Resonance Imaging (MRI) for prediction of LN involvement in locally advanced cervical cancer (LACC). A total of 55 cases diagnosed with LACC (IIB-IVA FIGO 2018) between 28 December 2010 and 30 October 2020 were evaluated in this retrospective study. LN involvement was evaluated in patients who underwent surgical staging and MRI. The prediction of LN involvement based on LN size on MRI was calculated statistically. The mean age of 55 patients was 56 (33-78) years. For the cases, 76.4% were stage IIB, 12.7% were stage III, and 10.9% were stage IVA. Squamous cell histological type was detected with a rate of 90.9%. The cut-off value for pelvic LN diameter on MRI in predicting pelvic LN involvement was 18.5 mm, and the sensitivity and specificity values were calculated as 50.0% and 93.6%, respectively (p=0.027). The cut-off value for pelvic and para-aortic LN diameter on MRI in predicting pelvic and para-aortic LN involvement was 17.0 mm with a sensitivity of 41.7% and specificity of 88.4% (p=0.081). In LACC, prediction of LN involvement by LN diameter detected on MRI has moderate sensitivity and high specificity with a cut-off value of 17.0 mm.

Fluorodeoxyglucose positron emission tomography (18F-FDG PET)-computed tomography (CT) in the initial staging of bladder cancer: a single institution experience

BackgroundThe purpose of this study was to assess the usefulness of fluorodeoxyglucose positron emission tomography (18F-FDG PET)-computed tomography (CT) scan for staging urinary bladder cancer. The study also sought to determine the effect of 18F-FDG PET/CT on management decisions and its implications for patient care.MethodsA total of 133 patients with bladder cancer who had both conventional imaging and 18F-FDG PET/CT for initial staging were identified. All 18F-FDG-PET/CT findings were classified as true positive, true negative, false positive, or false negative based on their potential to impact the intent of treatment. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated using the standard definition. Furthermore, the rate of change in therapy intent was determined for the entire sample and for subgroups with non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) patients.ResultsThe overall concordance rate between PET/CT and conventional imaging was around 54%. On conventional images, 18% of patients had localized disease, which was upstaged in 6.8% of cases using 18F-FDG PET/CT. Pelvic lymph node involvement was detected in 18.8% of cases using conventional imaging, which was downstaged to localized disease in 4.5% of cases using 18F-FDG PET/CT. While 63.2% of patients had systemic disease on a CT scan, 24.7% of cases were downstaged using PET/CT. Overall, the rate of change in therapy intent was 26.3% for the entire sample, 24.5% for NMIBC subgroup, and 27.3% for MIBC patients.ConclusionsThe study found that 18F-FDG PET/CT is an effective and accurate tool for staging bladder cancer in newly diagnosed patients. Approximately one quarter of patients had a change in management intent based on 18F-FDG PET/CT results. The study suggests that PET/CT should be used as a standard for newly diagnosed patients, but more research is needed to confirm this.

Genitourinary embryonal rhabdomyosarcoma clinicopathologic determinants of clinical outcomes: Analysis of a pooled database.

e23536 Background: Embryonal rhabdomyosarcoma (ERS) refers to malignant soft tissue tumors with phenotypical, histological features of primitive skeletal muscle. ERS commonly involves the head and neck region and genitourinary system. Genitourinary embryonal rhabdomyosarcoma (GUERS) is considered an entity similar to other ERS based on Intergroup Rhabdomyosarcoma Study Group (IRSG) with non-prostate GUERS considered low risk. This study seeks to define other high-risk subtypes in this population. Methods: To study the demographic and molecular characteristics, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 137 cases of GUERS. Kaplan-Meier survival curves, Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS) and disease-free survival (DFS). Results: 137 patients with confirmed GUERS were identified: median age was 16 and F:M ratio of 1.6. Female reproductive organs (49%), renal and urinary tract (24%), male reproductive organs (23%), and abdomino-pelvis (4%) were involved. Lymph node involvement and metastasis occurred in 11% and 13%, respectively. Staging consisted of stage I (65%), stage II (15%), stage III (8%), and stage IV (12%). Rhabdomyosarcoma clinical groups were mostly IA (41%), IIIA (31%) and IV (13%). Risk groups consisted of low (71%), intermediate (17%), and high (13%). Median OS and DFS were 96 and 42 months, respectively. The primary site of involvement impacted OS, with urinary tract organ involvement having the best median OS, compared to female reproductive organs, male reproductive organs, and abdomino-pelvis involvement (p = 0.01). While primary pelvic disease (p = 0.03), prostate (p = 0.008), and lymph node involvement (p = 0.001) were associated with worse OS, cervix/vaginal involvement tended to have better OS (p = 0.06). Constitutional symptoms (p = 0.0007), obstruction (p = 0.047) and metastases (p = 0.02) were associated with worse OS. Clinical staging system (p = 0.0008), risk groupings (p = 0.06) correlated with OS, but not clinical groupings (p = 0.26). GUERS with vimentin+, CD99- and SMA+ had worse survival (only the latter was statistically significant). Compared to no treatment, RT, CT+/-RT, S+CT+RT were superior with mOS of 2, 6, NR, 96 months, respectively (p &lt; 0.0001). Achieving CR had superior OS (p &lt; 0.0001). OS was not impacted by age, sex, or extent of surgery. Conclusions: Genitourinary embryonal rhabdomyosarcoma is a distinct clinical entity with outcomes worse than other forms of ERS defined by the Clinical Groups of IRSG. Prostate, primary pelvic and obstructive symptoms have worse OS compared to bladder and cervical involvement and we propose their inclusion in the current Clinical Group. This study presents updated clinicopathologic data from a pooled cohort of patients with GUERS.

Management of lateral pelvic lymph nodes in rectal cancer.

Lateral pelvic lymph node (LPLN) involvement occurs in 10%-25% of rectal cancer cases. Total mesorectal excision (TME) with routine LPLN dissection (LPLND) is predominantly applied in Japan whereas TME with neoadjuvant treatment are used in the West. LPLND is a morbid procedure and minimally invasive techniques may help reduce its morbidity. Selective lateral pelvic node dissection with TME following neoadjuvant treatment achieves acceptable disease-free and overall survival.

A Prospective Study of Chemoradiotherapy as Primary Treatment in Patients With Locoregionally Advanced Penile Carcinoma

Neoadjuvant chemotherapy followed by surgery for locoregionally advanced penile carcinoma (LAPSCC) is associated with severe toxicity and a 1-year survival probability of ∼50%. We aimed to evaluate the safety and efficacy of chemoradiotherapy (CRT) as the primary treatment for LAPSCC and the association of high-risk human papillomavirus (hrHPV) with the outcome. This was a prospective, single-center, single-arm study of CRT in LAPSCC, defined as a large/inoperable primary tumor, large palpable nodes, suspicion of extranodal extension or pelvic nodal involvement, and no distant metastases. CRT consisted of 49.5 Gy (33×1.5 Gy) on affected inguinal and pelvic areas combined with intravenous mitomycin C on day 1 and capecitabine on radiation days. Primary tumors and positron emission tomography/computed tomography-positive deposits received a boost of 59.4 Gy (33×1.8 Gy). The response was evaluated by 18F-fluorodeoxyglucose positron emission tomography/computed tomography. If feasible, patients with residual/recurrent disease underwent salvage surgery. The primary endpoint was 1-year progression-free survival (PFS), reached when 1-year PFS was ≥50%. Other endpoints were 2-year PFS, overall survival, and toxicity rates. Kaplan-Meier survival curves were compared using the log-rank test. Thirty-three patients were included: 29 (88%) with stage IV disease (T4 any-N M0 and/or any-T N3 M0) and 8 (24%) with hrHPV-positive disease. Median follow-up was 41 months. Thirty-two completed CRT. Eleven (33%) experienced ≥1 grade 3 treatment-related adverse event. There were no grade 4 or 5 treatment-related events. Twenty-four patients (73%) responded, including 13 (39%) complete responses. Nine patients (27%) underwent salvage surgery, and an additional 8 patients underwent later surgery (together 52%). One- and 2-year PFS were 34% and 31%, respectively. One- and 2-year overall survival were 73% and 46%, respectively. No significant difference between patients with hrHPV-positive and -negative tumors was observed. CRT is a viable treatment option for LAPSCC with acceptable toxicity. CRT can result in an enduring response. If patients have residual tumor, salvage surgery is feasible. HrHPV status was not associated with outcomes.