Trimodal therapy vs. radical cystectomy for muscle-invasive bladder cancer: A Markov microsimulation model

Introduction: Radical cystectomy (RC) is the historic gold standard treatment for muscle-invasive bladder cancer (MIBC), but trimodal therapy (TMT) has emerged as a valid therapeutic option for selected patients. Given that prospective clinical trials have been difficult to perform in this area, our aim was to compare these two primary treatment strategies using decision analytic methods. Method: A two-dimensional Markov microsimulation model was constructed using TreeAge Pro to compare RC and TMT for patients with newly diagnosed MIBC. A comprehensive literature search was used to populate model probabilities and utilities. Our primary outcome was quality-adjusted life expectancy (QALE). Secondary outcomes included crude life expectancy (LE) and bladder cancer recurrences. The simulated patient for our model was an adult with MIBC (pT2-4 N0 M0) who was a candidate for either RC or TMT. Results: A total of 500 000 patients were simulated. TMT resulted in an estimated mean QALE of 7.48 vs. 7.41 for RC. However, the average LE for patients treated with TMT was lower compared with RC (10.20 vs. 10.74 years). A sensitivity analysis evaluating the impact of age showed that younger patients treated with RC had greater QALE and longer LE than those treated with TMT; inverse findings were observed for elderly patients. Overall, 39.4% of patients treated with TMT experienced a bladder recurrence. Conclusions: RC results in a longer LE compared to TMT (0.54 years), but with a lower QALE (-0.07 years). The preferred treatment strategy varied with patient age.

Comparing Prognosis Associated with Partial Cystectomy and Trimodal Therapy for Muscle-Invasive Bladder Cancer Patients

<b><i>Objective:</i></b> This study aimed to compare the survival outcomes between trimodal therapy (TT) and partial cystectomy (PC) in muscle-invasive bladder cancer (MIBC) patients. <b><i>Methods:</i></b> The data of 13,096 patients with MIBC diagnosed between 2004 and 2015 were retrieved from the Surveillance, Epidemiology, and End Results database. Among them, 4,041 patients underwent TT and 1,670 patients underwent PC. Propensity score matching was performed to balance the characteristics between the 2 treatment groups. A multivariate Cox regression analysis model and a competing risk model were used to evaluate overall survival (OS) and cancer-specific survival. Cumulative incidence survival curves were obtained using the Kaplan-Meier method. <b><i>Results:</i></b> Results of multivariate Cox analysis before propensity score matching showed that the TT group had a 31% reduction in cause-specific survival relative to the PC group (HR: 0.69, 95% CI: 0.61–0.78, <i>p</i> &#x3c; 0.001) and a 28% reduction in OS (HR: 0.72, 95% CI: 0.66–0.79, <i>p</i> &#x3c; 0.001). After propensity score matching, the 2 groups yielded 972 patients, with 3-year cause-specific survival rates of 54.1% and 68.5% in the TT group and the PC group, respectively. <b><i>Conclusions:</i></b> Patients who underwent PC had a better prognosis than those who received TT. In addition, for MIBC patients who required bladder-sparing therapy, advanced age (≥80 years), pathological type of squamous cell carcinoma, and tumor stage of T3–4, N2–3, and M1 were independent poor prognostic factors.

Physical therapies in the decongestive treatment of lymphedema: A randomized, non-inferiority controlled study

Objective: To assess whether the treatment with intermittent pneumatic compression plus multilayer bandages is not inferior to classical trimodal therapy with manual lymphatic drainage in the decongestive lymphedema treatment. Study Design: Randomized, non-inferiority, controlled study to compare the efficacy of three physical therapies’ regimens in the Decongestive Lymphatic Therapy. Participants: 194 lymphedema patients, stage II–III with excess volume > 10% were stratified within upper and lower limb and then randomized to one of the three treatment groups. Baseline characteristics were comparable between the groups. Intervention: all patients were prescribed 20 sessions of the following regimens: Group A (control group): manual lymphatic drainage + Intermittent Pneumatic Compression + Bandages; Group B: pneumatic lymphatic drainage + Intermittent Pneumatic Compression + Bandages; and Group C: only Intermittent Pneumatic Compression + Bandages. End-point: Percentage reduction in excess volume (PREV). Results: All patients improved after treatment. Global mean of PREV was 63.9%, without significant differences between the groups. The lower confidence interval of the mean difference in PREV between group B and group A, and between group C and group A were below 15%, thus meeting the non-inferiority criterion. Most frequent adverse events were discomfort and lymphangitis, without differences between groups. A greater baseline edema, an upper-limb lymphedema and a history of dermatolymphangitis were independent predictive factors of worse response in the multivariate analysis. Conclusions: Decongestive lymphatic therapy performed only with intermittent pneumatic compression plus bandages is not inferior to the traditional trimodal therapy with manual lymphatic drainage. This approach did not increase adverse events.

Factors affectıng recurrence after trımodal treatment ın ınvasıve bladder cancer

Background In this study, we aimed to determine which patients will benefit most from TMT treatment, and to evaluate the factors affecting relapse, survival and response to treatment separately. Methods For the study, patients who presented to our hospital’s outpatient clinic between 2010 and 2020 and were diagnosed with locally advanced (T2-G3) invasive urothelial bladder cancer and treated with gemcitabine concomitantly with radiotherapy following complete TUR were identified. A total of 112 patients with transitional cell bladder cancer invading the muscle were enrolled in the study including 88 (78.6%) males and 24 (21.4%) females. Results Tumor location was significantly associated with tumor recurrence (p = 0.003). Recurrence at follow-up was significantly associated with the number of tumor foci (p = 0.008). Median duration of follow-up and median progression-free survival were 41.50 months and 65 ± 4.21 (95% CI, 56.74-73.25) months, respectively. Progression-free survival was not statistically significantly associated with neutrophil/lymphocyte ratio (NLR), platelet/ lymphocyte ratio (PLR) or BMI (p = 0.32, p = 0.47, p = 0.39, respectively), but muscle invasion during follow-up was significantly associated with progression-free survival (p = 0.009). Conclusions Tumor location, the number of tumor foci, history of multiple transurethral resection surgeries and a NLR ≥ 2.56 were significantly associated with recurrence following Trimodal therapy (TMT). A lower rate of recurrence was observed among patients undergoing early TMT after initial diagnosis. None of the patients treated with trimodal therapy experienced severe adverse effects. Therefore, trimodal therapy is a safe, effective and tolerable therapeutic option with a low rate of recurrence in selected eligible patients.

Application of contrast-enhanced CT radiomics in prediction of early recurrence of locally advanced oesophageal squamous cell carcinoma after trimodal therapy

Background Early recurrence of oesophageal squamous cell carcinoma (SCC) is defined as recurrence after surgery within 1 year, and appears as local recurrence, distant recurrence, and lymph node positive and disseminated recurrence. Contrast-enhanced computed tomography (CECT) is recommended for diagnosis of primary tumor and initial staging of oesophageal SCC, but it cannot be used to predict early recurrence. It is reported that radiomics can help predict preoperative stages of oesophageal SCC, lymph node metastasis before operation, and 3-year overall survival of oesophageal SCC patients following chemoradiotherapy by extracting high-throughput quantitative features from CT images. This study aimed to develop models based on CT radiomics and clinical features of oesophageal SCC to predict early recurrence of locally advanced cancer. Methods We collected electronic medical records and image data of 197 patients with confirmed locally advanced oesophageal SCC. These patients were randomly allocated to 137 patients in the training cohort and 60 in the test cohort. 352 radiomics features were extracted by delineating region-of-interest (ROI) around the lesion on CECT images and clinical signature was generated by medical records. The radiomics model, clinical model, the combined model of radiomics and clinical features were developed by radiomics features and/or clinical characteristics. Predicting performance of the three models was assessed with area under receiver operating characteristic curve (AUC), accuracy and F-1 score. Results Eleven radiomics features and/or six clinical signatures were selected to build prediction models related to recurrence of locally advanced oesophageal SCC after trimodal therapy. The AUC of integration of radiomics and clinical models was better than that of radiomics or clinical model for the training cohort (0.821 versus 0.754 or 0.679, respectively) and for the validation cohort (0.809 versus 0.646 or 0.658, respectively). Integrated model of radiomics and clinical features showed good performance in predicting early recurrence of locally advanced oesophageal SCC for both the training and validation cohorts (accuracy = 0.730 and 0.733, and F-1score = 0.730 and 0.778, respectively). Conclusions The integrated model of CECT radiomics and clinical features may be a potential imaging biomarker to predict early recurrence of locally advanced oesophageal SCC after trimodal therapy.

Trimodal therapy with high-dose-rate brachytherapy and hypofractionated external beam radiation combined with long-term androgen deprivation for unfavorable-risk prostate cancer

Purpose To assess the outcomes of high-dose-rate (HDR) brachytherapy and hypofractionated external beam radiation therapy (EBRT) combined with long-term androgen deprivation therapy (ADT) in very-high-risk (VHR) versus high-risk (HR) prostate cancer (PCa), as defined in the National Comprehensive Cancer Network (NCCN) criteria. Methods Data from 338 consecutive HR or VHR PCa patients who had undergone this tri-modal therapy between 2005 and 2018 were retrospectively analyzed. Biochemical recurrence (BCR)-free, progression-free, overall, and cancer-specific survival (BCRFS/PFS/OS/CSS) rates were analyzed using the Kaplan–Meier method and Wilcoxon test. Cox regression models were used to evaluate candidate prognostic factors for survival. C‑indexes were used to assess model discrimination. Results Within a median follow-up of 84 months, 68 patients experienced BCR, 58 had disease progression including only 3 with local progression, 27 died of any cause, and 2 died from PCa. The 5‑year BCRFS, PFS, OS, and CSS rates were 82.2% (HR 86.5%; VHR 70.0%), 90.0% (HR 94.3%; VHR 77.6%), 95.7% (HR, 97.1%; VHR, 91.8%), and 99.6% (HR, 100%; VHR, 98.0%), respectively. In multivariable analyses that adjusted for standard clinicopathologic features, the risk subclassification was associated both PFS and OS (p = 0.0003 and 0.001, respectively). Adding the risk subclassification improved the accuracy of models in predicting BCRFS, PFS, and OS. Conclusion While the outcome of this trimodal approach appears favorable, VHR PCa patients had significantly worse oncological outcomes than those with HR PCa. The NCCN risk subclassification should be integrated into prognostic tools to guide risk stratification, treatment, and follow-up for unfavorable PCa patients receiving this trimodal therapy.