Tadas Latkauskas

Background and Objectives: Rectal cancer management has changed substantially over the past two decades. We evaluated 20-year trends in stage at diagnosis, treatment patterns, and survival at a Lithuanian tertiary referral centre. Materials and Methods: This retrospective cohort study included 839 patients who underwent resection for stage I–III rectal cancer between 2004 and 2023, divided into two periods: 2004–2013 (n = 426) and 2014–2023 (n = 413). Survival was analysed with Kaplan–Meier estimates and Cox proportional hazards regression, truncated at 60 months. Results: Patients in the later cohort were diagnosed at an earlier clinical stage (stage I: 12.6% vs. 2.4%) and more often received neoadjuvant or perioperative therapy (55.2% vs. 37.1%; p < 0.001). Among clinical stage III patients, receipt of neoadjuvant chemoradiotherapy or total neoadjuvant treatment rose from 15.9% to 70.9% (p < 0.001), while pathological complete response among treated patients remained stable (10.8% vs. 10.7%; p = 0.98). Five-year overall survival increased from 64.8% to 71.3% (HR 0.77; 95% CI 0.60–0.99; p = 0.039) and cancer-specific survival from 70.4% to 80.8% (HR 0.60; 95% CI 0.45–0.80; p = 0.0005). The cohort effect persisted after multivariable adjustment for CSS (HR 0.62; 95% CI 0.45–0.85; p = 0.003), with clinical stage explaining only ~13% of the crude effect; stage III sensitivity analysis confirmed the CSS gain (67.9% to 77.3%; p = 0.009). Conclusions: Cancer-specific survival improved substantially and independently of stage migration. The gain coincided with markedly wider and better-targeted delivery of effective neoadjuvant therapy rather than with improved per-patient tumour responsiveness. As an observational comparison of two historical cohorts, this study demonstrates association rather than causation; nonetheless, it provides real-world evidence consistent with the hypothesis that systematic implementation of evidence-based rectal cancer pathways translates into measurable survival benefit.

Background: Locally advanced rectal cancer (LARC) treatment selection between neoadjuvant intensified chemotherapy (NIC) and standard chemoradiotherapy (CRT) lacks validated predictive biomarkers. Interleukin-1β (IL1B) polymorphisms modulate IL-1β expression and may influence treatment-specific outcomes through tumor microenvironment remodeling. Methods: In this prospective, single-center, randomized, open-label noninferiority trial (NCT05378919), 150 patients with stage II–III rectal cancer were randomized 1:1 to NIC (FOLFOX4, 8 cycles; n=68) or CRT (50 Gy/25 fractions with concurrent fluoropyrimidine; n=82). The primary endpoint was 5-year disease-free survival (DFS; noninferiority margin HR ≤1.29, NIC vs. CRT). IL1B rs1143634 and rs16944 were genotyped by TaqMan assay. Treatment–genotype interactions were assessed using Cox regression with multiplicative interaction terms. Results: Noninferiority was not demonstrated: 5-year DFS was 54.4% (NIC) versus 68.1% (CRT) in the ITT population (HR 1.52, 95% CI 0.90–2.56; p=0.114), with the upper CI bound exceeding the prespecified margin of 1.29. Per-protocol DFS was significantly inferior for NIC (62.5% vs. 82.1%; HR 2.27, 95% CI 1.06–4.76; p=0.029). Overall survival and cancer-specific survival (CSS) did not differ significantly between arms. A statistically significant treatment–genotype interaction was identified for rs1143634 in CSS (interaction p<0.001): T-allele carriage (CT+TT) was associated with inferior CSS exclusively in the NIC arm (HR 4.84, 95% CI 1.04–22.43; p=0.044), with no prognostic effect in the CRT arm (HR 0.69; p=0.494). A DFS interaction was also significant (p=0.047). rs16944 showed a borderline CSS interaction (p=0.082). Conclusions: NIC (FOLFOX4) did not achieve DFS noninferiority versus CRT in unselected LARC patients. IL1B rs1143634 demonstrates a treatment-arm-specific prognostic effect on cancer-specific survival, with a highly significant treatment–genotype interaction (p<0.001) identified within a prospective randomized design with prespecified translational hypotheses, satisfying the formal criterion for predictive biomarker classification. Prospective validation in an adequately powered, biomarker-stratified trial is warranted.

Introduction. Vulvar carcinoma is a rare malignancy, whereas rectal cancer is a more common oncological condition. However, the simultaneous occurrence of these two diseases is exceptionally rare. Case presentation. A 76-year-old woman presented with rectal bleeding and was previously diagnosed with keratinizing squamous cell carcinoma G1 of the vulva, unrelated to HPV. Imaging revealed tumor-like masses in the vulva and rectum, with pathological lymph nodes. Biopsy confirmed rectal adenocarcinoma in situ. She underwent obstructive rectal resection, colostomy formation, vulvar resection, and lymphadenectomy. Postoperative antibiotic therapy was administered and discontinued after seven days due to stable inflammatory markers. The patient was discharged in good condition, with planned rehabilitation in a sanatorium. Conclusion. Rectal adenocarcinoma and vulvar keratinizing squamous cell carcinoma concurrent occurrence is very rare. The risk factors for vulvar cancer (HPV, smoking, immunosuppression, lichen sclerosus) and rectal cancer (genetic predispositions, lifestyle factors (e.g., smoking, alcohol consumption), inflammatory bowel diseases) differ. However, genetic syndromes and certain interactions between lifestyle factors may lead to the concurrent occurrence of these two tumors. Given the complexity of managing two primary tumors, a multidisciplinary surgical approach was essential in our case. Further research is needed to explore possible biological links and optimize diagnostic and treatment strategies for such rare oncological presentations.

There still is no evidence which neoadjuvant therapy regimen for stage II–III rectal cancer is superior. The aim of this study was to compare results achieved after long-course chemoradiotherapy (CRT) with short-term radiotherapy (RT) followed by delayed surgery. A randomized trial was carried out between 2007–2013. One hundred fifty patients diagnosed with stage II–III rectal cancer were randomized into one of two neoadjuvant treatment arms: conventional chemoradiotherapy (CRT) and short-term radiotherapy (RT) followed by surgery after 6–8 weeks. Primary endpoints of this trial were downstaging and pathological complete response rate. Secondary endpoints were local recurrence rate and overall survival. The pathological complete response was found in 3 (4.4%) cases after RT and 8 (11.1%) after CRT (P = 0.112). Downstaging (stage 0 and I) was observed in 21 (30.9%) cases in RT group vs. 27 (37.5%) cases in CRT group (P = 0.409). Median follow-up time was 39.7 (range 4.9–79.7) months. 3-years overall survival (OS) was 78% in RT group vs. 82.4% in CRT group (P = 0.145), while disease-free survival (DFS) differed significantly – 59% in RT group vs. 75.1% in CRT group (P = 0,022). Hazard ratio of cancer progression for RT patients was 1.93 (95% CI: 1.08–3.43) compared to CRT patients. Three-years disease-free survival was better in CRT group comparing with RT group with no difference in overall survival. http://clinicaltrials.gov identifier NCT00597311. January 2008.