Background and objectives: This study aimed to evaluate prognostic factors for post-recurrence survival in local and locally advanced colorectal cancer patients. Materials and Methods: A total of 273 patients with stage III and high-risk stage II colorectal cancer were prospectively enrolled. All patients underwent operative treatment of the primary tumor and adjuvant fluorouracil-based chemotherapy. Results: Over the three-year period (2008–2010), a cohort of 273 patients with stage III and high-risk stage II colorectal cancer had been screened. During follow up, 105 (38.5%) patients had disease recurrence. Survival rates 1-, 3- and 5-year after recurrence were 53.9, 18.2 and 6.5%, respectively, and the median post-recurrence survival time was 13 months. Survival analysis showed that age at diagnosis (p < 0.01), gender (p < 0.05), elevated postoperative Ca19-9 (p < 0.01), tumor histology (adenocarcinoma vs. mucinous vs. signet ring tumors, p < 0.01) and tumor stage (II vs. III, p < 0.05) had a significant influence on post-recurrence survival. Recurrence interval and metastatic site were not related to survival following recurrence. Multivariate analysis showed that older age (HR 2.43), mucinous tumors (HR 1.51) and tumors expressing Ca19-9 at baseline (HR 3.51) were independently associated with survival following recurrence. Conclusions: Baseline patient and tumor characteristics largely predicted patient outcomes after disease recurrence. Recurrence intervals in local and locally advanced colorectal cancer were not found to be prognostic factors for post-recurrence survival. Older age, male gender, stage III and mucinous histology were poor prognostic factors after the disease had recurred. Stage II patients had remarkable post-recurrence survival compared to stage III patients.

Purpose: Early-onset colorectal cancer (CRC) is a growing problem. The aim of the study was to identify adolescent and young adult (AYA) patients with CRC in Serbia, treated in the single tertiary cancer center. Materials and Methods: This is a retrospective study that included only AYA patients (ages 18–39 years) with histologically confirmed CRC. In 11 year (2009–2019), 109 patients were identified from a single-institution database and their clinical variables and outcomes were analyzed. Results: The prevalence of a positive family history of CRC was 12.8%. Presenting symptoms were not different than traditional CRC. More than a quarter were diagnosed as an emergency. Left-sided tumors were diagnosed in 83.4% and mucinous tumors were recorded in one-third of the patients. Postoperatively patients mainly were in PS0–1 (97%). Patients presented as stages II (18.3%), III (47.7%), and IV (33.9%). The recurrence rate in local stages was 50%. Surgical treatment of localized metastatic disease was performed in almost half of the stage IV patients. Median disease-free survival for patients with the recurrent disease was 11.8 months. Median overall survival (OS) for the local and metastatic stage was 64.3 and 20.5 months, respectively. Survival analysis showed that performance status, bowel obstruction, N2 status, local invasions, disease stage, and surgery in stage IV had a statistically significant influence on OS. Conclusion: Serbian AYA CRC patients are of good general condition, with advanced left-sided tumors, common mucinous histology, and inverse histology features. Surgery in metastatic disease provided long-term survival. The outcome of the patient is influenced by a late diagnosis, inverse histological features, and treatment provided.

Background: It is projected that, by 2040, the number of new cases of colorectal cancer (CRC) will increase to 3.2 million, and the number of deaths to 1.6 million, highlighting the need for prevention strategies, early detection and adequate follow-up. In this study, we aimed to provide an overview of the progress in personalized medicine of CRC in Serbia, with results and insights from the Institute for Oncology and Radiology of Serbia (IORS), and to propose guidance for tackling observed challenges in the future. Methods: Epidemiological data were derived from official global and national cancer registries and IORS electronic medical records. Germline genetic testing for Lynch syndrome was performed by Next Generation Sequencing. RAS and BRAF mutation analyses were performed using qPCR diagnostic kits. Results: Epidemiology and risk factors, prevention and early detection programs, as well as treatment options and scientific advances have been described in detail. Out of 103 patients who underwent germline testing for Lynch syndrome, 19 (18.4%) showed a mutation in MMR genes with pathogenic or likely pathogenic significance and 8 (7.8%) in other CRC-associated genes (APC, CHEK2, MUTYH). Of 6369 tested patients, 50.43% had a mutation in KRAS or NRAS genes, while 9.54% had the V600 mutation in the BRAF gene. Conclusions: Although significant improvements in CRC management have occurred globally in recent years, a strategic approach leading to population-based systemic solutions is required. The high incidence of young-onset CRC and the growing elderly population due to a rise in life expectancy will be especially important factors for countries with limited healthcare resources like Serbia.

Background/Objectives: The global burden of colorectal cancer (CRC) is projected to increase by 2040, highlighting the need for prevention strategies, early detection and adequate follow. The aim of this study was to provide an overview of the progress in personalized medicine of CRC in Serbia, with results and insights from the Institute for Oncology and Radiology of Serbia (IORS), and to propose guidance for tackling observed challenges in the future. Methods: Epidemiological data was derived from official global and national cancer registries and IORS electronic medical records. Germline genetic testing for Lynch syndrome was performed by Next Generation Sequencing. RAS and BRAF mutation analyses were performed using qPCR diagnostic kits. Results: Epidemiology and risk factors, prevention and early detection programs, as well as treatment options and scientific advances have been described in detail. Out of 103 patients who underwent germline testing for Lynch syndrome, 19 (18.4%) had a pathogenic or likely pathogenic mutation in one of the MMR genes, and 8 (7.8%) in other CRC-associated genes (APC, CHEK2, MUTYH). Of 6369 tested patients, 50.43% had a mutation in KRAS or NRAS genes, while 9.54% had the V600 mutation in the BRAF gene. Conclusions: Although significant improvements in CRC management have occurred globally in recent years, the high incidence of young-onset CRC and the growing elderly population due to a rise in life expectancy require a strategic approach leading to population-based systemic solutions, especially important for countries with limited health care resources as Serbia.

Introduction: Early-onset colorectal cancer (EOCRC) is increasing worldwide, with Serbia showing a similar incidence compared to global trends. Precise mutation genotyping has gained importance following the recent approval of KRAS -specific inhibitors. Although KRAS , NRAS , and BRAF testing is routinely performed in Serbia, specific mutation subtypes in EOCRC patients have not yet been published. This retrospective cohort study aimed to investigate temporal trends in EOCRC incidence in Serbia and characterize the mutational profile of KRAS , NRAS , and BRAF in EOCRC patients. Methods: National cancer registry data from 2016 to 2022 were analyzed to assess EOCRC incidence trends. Molecular testing for KRAS , NRAS , and BRAF was performed on 681, 420, and 67 EOCRC patients, respectively, using qPCR-based diagnostic assays, complemented by Sanger sequencing on 54 cases to characterize KRAS exon 2 and BRAF V600E mutations. Results: Registry data revealed a consistent upward trend in EOCRC incidence, especially in the 45-49 years’ age group. In the qPCR-tested cohort, KRAS mutations were detected in 44.3% (302/681), NRAS in 6.4% (27/420), and BRAF in 8.9% (6/67). In the sequenced subset, KRAS mutations were found in 20.4%, including G12D (36.4%), G13D (27.3%), G12 C (18.1%), and G12S/G12 V (9.1%) variants. BRAF V600E was detected in 3.7%. Conclusions: We report a rise in EOCRC in Serbia, especially in ages 45-49, and recommend policy makers to lower the screening age to 45. We present the first detailed molecular profile of Serbian EOCRC and recommend that policy makers implement routine KRAS variant testing and ensure access to KRAS G12C-targeted therapies to improve personalized care.

Background: Single-agent pembrolizumab represents a standard of care in the first-line treatment of patients with metastatic non-small cell lung cancer (mNSCLC) with a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) of ≥50%. Real-world evidence is of increasing importance in oncology, as clinical trial inclusion criteria may not be truly reflective of the patient population seen in daily clinical practice. Methods: We performed a prospective–retrospective single-center study including 121 patients who received pembrolizumab as a first-line therapy for mNSCLC with a PD-L1 TPS ≥ 50%. Our aims were to make a comparison with published clinical trial results by assessing the efficacy and safety of pembrolizumab monotherapy in our population. We collected patient demographics, clinical characteristics of the disease, and treatment outcomes, including efficacy and safety. Results: A total of 121 patients were included, with a median follow-up of 40.77 months. The median progression-free survival in the real world (rwPFS) was 20.73 months (95% CI 12.24–29.22), and the median overall survival (OS) was 29.30 months (95% CI 16.57–42.04). Immune-mediated adverse events (irAEs) occurred in 42% of patients, with serious events (grade 3 or more) occurring in 12%. ECOG PS 2, male gender, squamous histology, pleural and visceral metastases, and treatment with corticosteroids prior to initiation of pembrolizumab were found to be negative predictors for overall survival, while the occurrence of irAEs was the predictor of longer survival. Conclusions: This study provides further real-world insights into the efficacy of pembrolizumab in a heterogeneous patient population with advanced NSCLC in a single center in Serbia. It also confirmed the value of good ECOS PS and the occurrence of irAEs as predictors of favorable outcomes.