Cisplatin-based neoadjuvant chemotherapy (NACT) followed by radical cystectomy (RC) is the standard treatment for eligible patients with muscle-invasive bladder cancer (MIBC). However, the comparative effectiveness of gemcitabine/cisplatin (GC) and dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) in routine practice remains insufficiently defined, particularly in broader real-world populations that include patients with regional lymph node involvement. We conducted a multicenter retrospective real-world study of 232 patients with non-metastatic urothelial MIBC treated with cisplatin-based NACT at seven Polish reference cancer centers between 2016 and 2024. One hundred patients received ddMVAC and 132 received GC. We compared pathological response, treatment toxicity, event-free survival (EFS), and overall survival (OS). EFS was defined as the time from NACT initiation to progression during neoadjuvant treatment, failure to undergo RC due to progression or treatment-related deterioration, recurrence after RC, or death from any cause. Univariable and multivariable Cox regression analyses were performed. Cumulative cisplatin dose was assessed using a cutoff of 280 mg/m². Baseline characteristics were generally comparable, although patients treated with ddMVAC had better ECOG performance status. Median treatment duration was shorter with ddMVAC than with GC (6.3 vs. 9 weeks; p < 0.001), while cumulative cisplatin dose was higher (280 vs. 210 mg/m²; p = 0.002). Pathological complete response (pCR) was achieved more frequently with ddMVAC than with GC (39.8% vs. 13.6%; p < 0.001). Median OS was longer in the ddMVAC group (39 vs. 27 months; p = 0.0203), and median EFS was also superior (not reached vs. 20.1 months; p = 0.001). In multivariable analysis, pCR remained independently associated with both OS and EFS, while R0 resection remained independently associated with EFS. Hematologic toxicity and treatment discontinuation due to toxicity were more frequent with GC. In this real-world cohort, ddMVAC was associated with a markedly higher pCR rate than GC. pCR was the strongest independent factor associated with favorable long-term outcomes, while R0 resection was independently associated with improved EFS. These findings support treatment strategies aimed at maximizing pathological response and ensuring timely radical surgery.

e16579 Background: Neoadjuvant chemotherapy (NACT) in patients (pts) with muscle-invasive bladder cancer (MIBC) significantly improves treatment outcomes. Widely used NACT regimen based on 3-4 cycles of gemcitabine and cisplatin (GC) before radical cystectomy (RC) remained the standard of care until the complete results of the VESPER trial, which demonstrated the superiority of 6 cycles of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) in terms of progression-free survival (PFS), complete pathological responses (pCR) and overall survival (OS). In most clinical trials, pts with clinically positive lymph nodes (N+ according to TMN) were underrepresented. The aim of the study is to compare the effectiveness and safety of the mentioned NACT regimens in real medical practice. Methods: Pts from 7 urooncology hospitals in Poland with MIBC stage ≥T2, cM0 treated with NACT GC or ddMVAC (11/2016-09/2024) were included. Pts from clinical trials were excluded. Complete clinical data were collected. Survival analyses were performed using the Kaplan-Meier method, Log-rank and chi-square or Fisher's tests were used for comparison between groups. Data cut-off was 31/12/2024. Results: Of the 261 pts treated with NACT, 232 were included in the analysis: 132 (57%) received GC, 100 (43%) ddMVAC). There were 55 (24%) women in the study groups, the median age was 67, cT2N0: 90 (39%), N+: 61 (27%), baseline anemia of any grade: 107 (48%). In the GC group, there were significantly more ECOG performance status (PS) 2 pts, p=0.0076, other variables did not differ significantly. Median total dose of cisplatin (MTDC) was significantly higher in ddMVAC group than in GC group (280 vs 210 mg/m2), p=0.0024. Median chemotherapy period was significantly longer in GC pts: 9 vs 6.3 weeks for ddMVAC, p=0.0007. RC was not performed in 35 (15%) of pts due to adverse events (AEs), progression, or withdrawal of consent. More objective pathological responses were achieved in the ddMVAC vs GC pts, 42 vs 14%, p<0,0001, however, there were no differences in clinical response. Significant difference in mOS between GP and ddMVAC group was observed: 27 vs 39m, p=0.0203. In univariate analysis, a significant advantage was also observed for MTDC ≥250mg/m2, p=0.0093; ECOG PS 0, p=0.0018; RC, p=0.01; R0 resection, p=0.001; and pCR, p<0.0001 in terms of OS. OS did not differ significantly between cT2N0 or >cT2N0 pts, p=0.3. Multivariate analysis confirmed a statistically significant OS benefit for ECOG PS 0, higher MDTC and pCR. More hematological AEs occured in the GC vs ddMVAC group: 98% vs 84%, p=0.0007. Conclusions: The use of NACT with the ddMVAC in MIBC pts showed a statistically significant improvement of OS compared to GC with favorable toxicity. The study indicates that the best prognosis is for pts with ECOG PS 0 who received a higher MTDC (preferably in the ddMVAC regimen), responded to NACT and underwent radical surgery regardless of the primary clinical stage of T and N.

In advanced-stage colorectal cancer (CRC), a strategy based on a sequence of systemic therapies brings survival benefits in most patients. Trifluridine and tipiracil hydrochloride (TT) is a chemotherapy drug effective in patients in the third- or later line setting. No highly specific biomarkers have been established for TT therapy so far. However, a systemic immune-inflammation index (SII), which is based on platelet, neutrophil and lymphocyte counts is applied to predict prognosis. In this retrospective, multicenter study, clinical data on 179 metastatic CRC patients treated with TT were collected. To evaluate factors predicting TT therapy response and overall survival, univariate logistic regression analysis was conducted. Subsequently, factors with p < 0.05 in univariate analysis were included in multivariate analysis. In the multivariate analysis of progression-free survival (PFS), three favorable parameters were significant: good to moderate histological differentiation (p = 0.0038), carcinoembryonic antigen (CEA) < 5 ng/L (p = 0.0316) and SII ≤ 550 (p = 0.007). Favorable prognostic factors revealed in the multivariate analysis of overall survival (OS) were: <3 prior lines of treatment (p = 0.02), good to moderate histological differentiation (p = 0.0003), CEA < 5 ng/L (p = 0.0227) and SII ≤ 550 (p = 0.0001). Our study indicated that pre-treatment SII may be clinically useful for selecting likely responder patients and assessing the prognosis for mCRC patients treated with TT.

Introduction. The BRAF mutation occurs in 8-12% of patients with colorectal cancer. This is associated with unfavorable prognosis - in metastatic disease, median survival does not exceed one year. Molecularly targeted treatment - encorafenib with cetuximab - is the standard of care in cases of chemotherapy failure. Material and methods. Medical data of 18 patients treated with encorafenib and cetuximab in 2021-2023 in 10 oncology centers in Poland were assessed. We analyzed clinical, pathomorphological, and molecular factors, as well as the effectiveness and safety of treatment. Results. The median age in the group was 63 years. Patients with metastases limited to one location predominated (78%). Treatment with encorafenib and cetuximab was used not only in the third (in 50% of patients) or fourth (in 28%) lines of treatment but also in the second (in 22%). The objective response rate was 29.4%, and the disease control rate was 76.4%. The median progression-free survival was 7.1 months. Four patients (22%) had a response lasting over 12 months. Conclusions. The results of the analysis confirmed the efficacy and safety of targeted treatment with encorafenib and cetuximab in patients with metastatic colorectal cancer with the BRAFV600E mutation, known from other studies.

Introduction: The BRAFV600E mutation is found in 6-11% of metastatic colo rectal cancer (mCRC) patients. Ac cording to international guidelines for BRAFV600Emutated mCRC, the triplet chemotherapy FOLFOXIRI (folinic acid, 5fluorouracil, oxaliplatin, irinotecan) or double chemotherapy with or with out bevacizumab, and encorafenib plus cetuximab should be considered in the first and second line settings. We aimed to evaluate clinical practices in BRAFV600Emutated mCRC patients treated at five Polish oncology centers. Material and methods: We retrospec tively analyzed the data of BRAFV600E mutated mCRC patients treated be tween 2011 and 2023. Before starting the first line treatment, all patients were tested for BRAF and RAS muta tions. Results: One hundred twentysix pa tients (median age: 68 years; 55% fe male, 45% male) from five oncology centers were included. The majority of patients (69, 55%) had a right sided primary tumor. The first line of chemo therapy was received by 100 patients (79.4%). The majority received doublet chemotherapy: FOLFOX (folinic acid, 5fluorouracil, oxaliplatin), FOLFIRI (folinic acid, 5fluorouracil, irinotecan), XELOX (capecitabine, oxaliplatin), and FOLFIRI with bevacizumab: 30 (30%), 47 (47%), 5 (5%), and 3 (3%). Only three patients received FOLFOXIRI; one pa tient received bevacizumab. The me dian duration of first line treatment was 5.26 months (95% CI: 0.03-18.9). Subsequently, 40%, 16%, 5%, and 1% of patients received second, third, fourth, and fifth line therapy, retrospec tively. During the median followup of 38.5 months, 96 (79.3%) patients died. The median overall survival from the time of mCRC diagnosis was 13.7 months (95% CI: 11.3-17.6). Conclusions: This study highlights the unmet need for effective treat ment strategies for patients with BRAFV600Emutated mCRC in Poland.

Progress in understanding complex interactions between cancer cells and the immune system has led to the development of new methods of treatment — immunotherapy, modulating the anti-cancer response of the immune system. For several years, colorectal cancer (CRC) was thought to be a cancer with low immune stimulation potential, but in recent years the favorable prognostic value of lymphocytic infiltrates in the tumor has been noted. Currently it is well known that the stimulation of the immune system by CRC cells is associated with the accumulation of mutations in DNA microsatellites. This phenomenon results from impairment of function of genes (mainly MLH1, MSH2, MSH6 and PMS2) encoding proteins involved in correction of mismatched nucleotides during replication (dMMR), whose phenotypic reflection is microsatellite instability (MSI). It affects about 15–20% of CRC, with clear differences depending on the stage of cancer — about 20% in stage II, 12% in stage III, and only around 4% in stage IV. dMMR/MSI cancers are highly immunogenic through overexpression of tumor antigens and can induce a deep immune response. Cancers with intact repair gene system (pMMR) and stable microsatellites (MSS) show poor immunogenicity, which makes it difficult to induce an anti-tumor immune response. The relationship between impairment of the mismatch repair system and the induction of an anti-cancer immune response justifies the use of checkpoint inhibitors of this response in the treatment of patients with CRC MSI/dMMR. In MSS/pMMR cancers, checkpoint inhibitors used in monotherapy are not effective. However, studies are underway to combine these drugs with other methods of systemic treatment (chemotherapy, EGFR inhibitors, angiogenesis inhibitors, MET inhibitors), as well as radiotherapy.

Progress in understanding complex interactions between cancer cells and the immune system has led to the development of new methods of treatment — immunotherapy, modulating the anti-cancer response of the immune system. For several years, colorectal cancer (CRC) was thought to be a cancer with low immune stimulation potential, but in recent years the favorable prognostic value of lymphocytic infiltrates in the tumor has been noted. Currently it is well known that the stimulation of the immune system by CRC cells is associated with the accumulation of mutations in DNA microsatellites. This phenomenon results from impairment of function of genes (mainly MLH1, MSH2, MSH6 and PMS2) encoding proteins involved in correction of mismatched nucleotides during replication (dMMR), whose phenotypic reflection is microsatellite instability (MSI). It affects about 15–20% of CRC, with clear differences depending on the stage of cancer — about 20% in stage II, 12% in stage III, and only around 4% in stage IV. dMMR/MSI cancers are highly immunogenic through overexpression of tumor antigens and can induce a deep immune response. Cancers with intact repair gene system (pMMR) and stable microsatellites (MSS) show poor immunogenicity, which makes it difficult to induce an anti-tumor immune response. The relationship between impairment of the mismatch repair system and the induction of an anti-cancer immune response justifies the use of checkpoint inhibitors of this response in the treatment of patients with CRC MSI/dMMR. In MSS/pMMR cancers, checkpoint inhibitors used in monotherapy are not effective. However, studies are underway to combine these drugs with other methods of systemic treatment (chemotherapy, EGFR inhibitors, angiogenesis inhibitors, MET inhibitors), as well as radiotherapy.

Cancers of the esophagus, esophageal-gastric junction or stomach are one of the most frequently diagnosed cancers in Europe and in the world. They are characterized by a poor clinical prognosis, hence it is necessary to look for new, more effective methods of their treatment. The dynamic development of immunotherapy based on immune checkpoint inhibitors such as antibodies blocking receptor proteins CTLA-4, PD-1 or ligand for the pro-grammed death receptor 1 (PD-L1) has led to a significant improvement in the effects of treatment of many cancers and initiated a number of studies evaluating the effectiveness and safety of immunotherapy in patients diagnosed with upper gastrointestinal cancer. The following paper presents the results of research that have become the basis for significant changes in the treatment strategy of patients with esophageal cell squamous carcinoma (ESCC), esophageal adenocarcinoma (EAC), adenocarcinoma of the esophagogastric junction (GEJ), gastric cancer, which are also reflected in the recommendations of oncological societies (NCCN, ASCO).

Sarcopenia is common in metastatic colorectal cancer (mCRC), increases the risk of treatment-related toxicity and reduces survival. Trifluridine/tipiracil (TT) chemotherapy significantly improved survival in refractory mCRC patients, but the prognostic and predictive role of pretherapeutic sarcopenia and variation in the skeletal muscle index (SMI) during this treatment has not been investigated so far. In this retrospective, observational study, clinical data on mCRC patients treated with TT at six cancer centres in Poland were collected. Computed tomography (CT) scans acquired at the time of initiation of TT (CT1) and on the first restaging (CT2), were evaluated. SMI was assessed based on the skeletal muscle area (SMA) at the level of the third lumbar vertebra. Progression-free survival (PFS) and overall survival (OS) were calculated from the treatment start. Neither initial sarcopenia nor ≥5% skeletal mass loss (SML) between CT1 and CT2 had a significant effect on PFS in treated patients (p = 0.5526 and p = 0.1092, respectively). In the multivariate analysis, reduced OS was found in patients with ≥5% SML (HR: 2.03 (1.11–3.72), p = 0.0039). We describe the prognostic role of sarcopenia beyond second line treatment and analyze other factors, such as performance status, tumor histological differentiation or carcinoembryonic antigen level that could predict TT treatment response.

Cytostatyki o kluczowym znaczeniu w strategii leczenia systemowego raka jelita grubego i odbytnicy to 5-fluorouracyl i kapecytabina. Kardiotoksycznośc związana z tymi lekami stanowi udokumentowane zdarzenie niepoządane. Mechanizm wywolujący kardiologiczne objawy uboczne zostal slabo poznany. W przebiegu stosowania fluoropirymidyn moze dochodzic miedzy innymi do skurczu naczyn wiencowych. W niniejszej pracy zaprezentowano opis chorej na raka odbytnicy, u ktorej doszlo do wystąpienia objawow ostrego zespolu wiencowego w trakcie leczenia 5-fluorouracylem. Objawy kardiotoksyczne pojawily sie mimo proby profilaktycznego zastosowania lekow naczyniorozkurczowych oraz po zmianie chemioterapetyku na doustną pochodną fluoropirymidyny — kapecytabine. Wystąpienie kardiologicznych zdarzen niepoządanych moze stwarzac duze trudności diagnostyczno-terapeutyczne i powodowac niepowodzenie leczenia. Potrzebny jest algorytm postepowania w takich przypadkach oparty na najlepszych dostepnych dowodach naukowych.