Predrag Nikic

Background: Organized cervical cancer screening aims to reduce the burden of advanced disease through earlier detection. However, a substantial proportion of women continue to present with locally advanced cervical cancer (LACC) requiring definitive chemoradiation. This study evaluated temporal changes in the demographic and clinicopathological characteristics of women with LACC treated with definitive chemoradiation before and after implementation of the organized cervical cancer screening program in Serbia. Methods: This retrospective single-center cohort study included 200 consecutive women with histologically confirmed LACC treated with definitive chemoradiation at the Institute of Oncology and Radiology of Serbia. Two cohorts were analyzed: a pre-screening cohort (2010–2011, n = 100) and a post-screening cohort (2022–2023, n = 100). Demographic and clinicopathological characteristics, including age, histopathology, FIGO stage, lymph node involvement, and geographic distribution, were compared. For study purposes, all patients were retrospectively restaged according to the FIGO 2018 classification using the best available clinical, radiological, and pathological data. Results: Women in the post-screening cohort were significantly older at diagnosis than those in the pre-screening cohort (mean age 54.9 vs. 49.7 years, p = 0.0046), with a substantially higher proportion of patients older than 64 years (28% vs. 2%, p < 0.0001). Although the overall distribution of FIGO stages II–IV did not differ significantly, a marked redistribution of FIGO 2018 substages was observed (p < 0.0001), characterized by an increased proportion of stage IIIC disease and significantly more frequent lymph node involvement (63% vs. 41%, p = 0.0018). Geographic distribution remained stable, with most patients referred from the Belgrade administrative district. Conclusions: This study demonstrated clinically relevant temporal changes in the demographic and clinicopathological characteristics of women requiring definitive chemoradiation for LACC in Serbia. More than a decade after implementation of organized cervical cancer screening, tertiary referral centers continue to manage a substantial burden of patients with locally advanced disease requiring complex, resource-intensive treatment. These findings should not be interpreted as a direct evaluation of the national screening program but may provide valuable insights for healthcare planning in Serbia and other countries with similarly resource-constrained healthcare systems. Strengthening participation in organized screening, ensuring timely diagnostic evaluation, and improving HPV vaccination uptake remain essential to reduce the burden of advanced cervical cancer.

Introduction: Patients with locally advanced cervical cancer (LACC) are commonly treated with definitive chemoradiotherapy (CRT), consisting of external beam radiotherapy (EBRT), concurrent chemotherapy, and brachytherapy. Advances in radiotherapy techniques and imaging over the past decade have led to important changes in treatment delivery. This study aimed to evaluate temporal changes in CRT delivery in patients with LACC. Methods: This retrospective single-center cohort study included 200 patients with LACC treated with definitive CRT at the Institute for Oncology and Radiology of Serbia. Two cohorts were analyzed: 100 patients treated in 2010-2011 and 100 patients treated in 2022-2023. Clinical and treatment-related parameters, including chemotherapy administration, EBRT technique, dose and fractionation, brachytherapy characteristics, and baseline patient characteristics, were compared. Results: Significant differences were observed between the two cohorts. The use of concurrent chemotherapy and the number of administered cycles differed significantly between the two cohorts (p < 0.001). A complete transition from conventional radiotherapy techniques to IMRT/VMAT was observed in the later period (p < 0.001), along with the introduction of simultaneous integrated boost (SIB). Differences were also identified in EBRT fractionation and total dose (p < 0.001). In brachytherapy, significant variations in dose and fractionation were observed (p < 0.001 and p < 0.05), while applicator type remained comparable. Conclusion: Significant temporal changes in CRT delivery were observed, reflecting the adoption of modern radiotherapy techniques and evolving treatment strategies. These findings indicate increasing treatment individualization and greater use of contemporary radiotherapy approaches in routine clinical practice within a middle-income setting.

Prostate cancer is one of the most prevalent malignancies in men, posing a significant public health challenge due to its high incidence and long-term treatment-related toxicities. Long-lived patients often experience prolonged side effects that can severely diminish their quality of life. Despite advancements in radiotherapy techniques like IMRT and VMAT, some patients still experience acute and late side effects. Current treatment protocols do not account for individual variability in normal-tissue radiosensitivity, highlighting the need for predictive tools and a personalised treatment approach. Genetic factors and molecular regulators like microRNAs (miRNAs) contribute to these variations by influencing DNA repair, inflammation, and apoptosis. This review explores potential biomarkers of radiotoxicity, focusing on immune-related factors such as IL-6 and TGF-β1, SNPs influencing radiosensitivity, miRNAs involved in radiation responses, and functional assays including the radiation-induced lymphocyte apoptosis (RILA) test. These approaches offer promising tools for identifying radiosensitive patients and enabling risk-adapted radiotherapy.

Background and Objectives: Radical prostatectomy (RP) stands as the predominant instigator of postoperative stress urinary incontinence. Techniques such as the preservation of the neurovascular bundles, bladder neck preservation, and ensuring longer postoperative urethral length have shown positive impacts on continence. The posterior reconstruction is another method that aids in early continence recovery. Anterior suspension as simulator of puboprostatic ligaments is another factor. Materials and Methods: This study was conducted in the Clinic of Urology, University Clinical Center of Serbia, between December 2014 and January 2020, employing a prospective, non-randomized comparative design. Data were meticulously gathered from 192 consecutive patients. The process of regaining continence was monitored at intervals of 1, 3, 6, 12, and 24 months after surgery. The main criterion for assessing the level of urinary continence was the number of pads used daily. Results: The distribution of overall continence rates in the BNP vs. no-BNP group at 3, 6 and 12 months was 86% vs. 60% (p < 0.0001), 89% vs. 67% (p < 0.0001), 93% vs. 83% (p = 0.022). Continence rates in non-posterior reconstruction group (10%, 22%, 34%, and 54% at 1, 3, 6, and 12 months) were statistically significantly lower (p < 0.0001). The patients who underwent urethral suspension exhibited significantly higher rates of overall continence at 1 mo (73% vs. 29%, p < 0.0001), 3 mo (85% vs. 53%, p < 0.001), 6 mo (89% vs. 62%, p < 0.0001), 12 mo (95% vs. 76%, p < 0.0001), and 24 mo (93% vs. 81%, p = 0.007). Patients who underwent urethral suspension had a four-fold greater likelihood of regaining continence (p = 0.015). Conclusions: Patients who underwent urethral suspension or BNP or posterior reconstruction had higher continence rates. Only the urethral suspension was found to be a significant prognostic factor of continence recovery.

Considering the divergent biological behaviors of certain histological subtypes of urothelial carcinoma, it would be of great importance to examine the impact of variant histology and to predict its presence in patients with bladder cancer. A single-center cohort study included 459 patients who underwent radical cystectomy for urothelial carcinoma between 2017 and 2021. Patients were followed up with until July 2022. We compared clinical, laboratory, and histopathologic characteristics and the overall survival between patients with pure urothelial carcinoma and variant histologies. Our results showed that the patients with variant histology were older and preoperatively more frequently had hydronephrosis and higher values of leukocytes and neutrophils. Also, we found a significant association between variant histology and an advanced stage of tumor disease, the presence of lymphovascular invasion, positive surgical margins, and metastases in surgically resected lymph nodes. The number of neutrophils was identified as an independent preoperative predictor of the presence of variant histology after a radical cystectomy. The overall survival of the patients with variant histology was significantly lower compared to the patients with pure urothelial carcinoma. According to our results, the presence of variant histology represents a more aggressive form of the disease. Preoperative neutrophil counts may indicate the presence of variant histology of urothelial carcinoma in patients with bladder cancer.

At the time when mass COVID-19 vaccination began, providing appropriate vaccination advice to uro-oncology patients became a challenge. This was a single-center cross-sectional observational study aimed to investigate the rate of COVID-19 vaccination among uro-oncology patients receiving systemic therapy for metastatic renal cell carcinoma and metastatic castration-resistant prostate cancer. Furthermore, we aimed to assess patients’ attitudes and identify factors influencing their decision to vaccinate against COVID-19. Data on patients’ sociodemographic characteristics, vaccination status, and awareness and attitudes about COVID-19 vaccination were collected from questionnaires completed by the patients. A total of 173 patients were enrolled in this study, and 124 (71.7%) of them completed the COVID-19 vaccination. Significantly higher vaccination rates were found in male patients, and also in older patients, highly educated patients, and those who lived with one household member. Furthermore, we found significantly higher vaccination rates in patients who had consulted with doctors involved in their treatment, particularly with urologists. A significant association was observed between COVID-19 vaccination and doctor’s advice, family member influence, and personal beliefs toward the vaccination. Our study showed multiple associations of patients’ sociodemographic characteristics with vaccination rates. Furthermore, consultation with doctors who are particularly involved in oncology treatment and advice received from them were associated with significantly higher vaccination rates among uro-oncology patients.

Background and Objectives: Oxidative stress induced by increased reactive oxygen species (ROS) production plays an important role in carcinogenesis. The entire urinary tract is continuously exposed to numerous potentially mutagenic environmental agents which generate ROS during their biotransformation. In first line defense against free radicals, antioxidant enzymes superoxide dismutase (SOD2) and glutathione peroxidase (GPX1) both have essential roles. Altered enzyme activity and decreased ability of neutralizing free oxygen radicals as a consequence of genetic polymorphisms in genes encoding these two enzymes are well described so far. This study aimed to investigate the association of GPX1 (rs1050450) and SOD2 (rs4880) genetic variants with the urothelial bladder cancer (UBC) risk independently and in combination with smoking. Furthermore, we aimed to determine whether the UBC stage and pathological grade were influenced by GPX1 and SOD2 polymorphisms. Material and Methods: The study population included 330 patients with UBC (mean age 65 ± 10.3 years) and 227 respective controls (mean age 63.4 ± 7.9 years). Single nucleotide polymorphism (SNP) of GPX1 (rs1050450) was analyzed using the PCR-RFLP, while SOD2 (rs4880) SNP was analyzed using the q-PCR method. Results: Our results showed that UBC risk was significantly increased among carriers of at least one variant SOD2 Val allele compared to the SOD2 Ala16Ala homozygotes (OR = 1.55, p = 0.03). Moreover, this risk was even more pronounced in smokers with at least one variant SOD2 Val allele, since they have even 7.5 fold higher UBC risk (OR = 7.5, p < 0.001). Considering GPX1 polymorphism, we have not found an association with UBC risk. However, GPX1 genotypes distribution differed significantly according to the tumor stage (p ˂ 0.049) and pathohistological grade (p ˂ 0.018). Conclusion: We found that SOD2 genetic polymorphism is associated with the risk of UBC development independently and in combination with cigarette smoking. Furthermore, we showed that GPX1 genetic polymorphism is associated with the aggressiveness of the disease.

The COVID-19 pandemic affected the functioning of health care systems, including emergency services worldwide. The aim of this study was to examine the impact of the pandemic and lockdown on the care of urgent urological patients in daily practice. Methods. Data were retrospectively collected from patients urgently hospitalized at Emergency Department of Clinic of Urology, University Clinical Center of Serbia, during the first three months of lockdown between Mar 15, 2020 and Jun 15, 2020, and compared to the same period in 2019. The collected data included demographic and clinical characteristics, as well as treatment characteristics and treatment outcomes. Results. This study included 80 patients who were hospitalized during the lockdown in 2020 and 68 patients who were hospitalized in the same period in 2019. There was no difference in total number of hospitalized patients, age and gender comparing these two periods. Among patients with urinary tract infection, the number of patients with urosepsis was significantly higher in 2020 (p = 0.028). The median time from symptoms onset to hospitalization was significantly longer in patients who were hospitalized in 2020 (p=0.049). No difference was found in duration of hospitalization and characteristics of treatment between two periods. The number of deaths was significantly higher in 2020 (p = 0.034). Conclusion. During lockdown in Serbia, patients applied to the emergency urology service significantly later. Furthermore, a higher number of patients with urosepsis and a higher number of deaths among hospitalized patients were found during lockdown compared to the previous year.

Background: The emerging new standard of care for metastatic clear cell renal carcinoma (mRCC) becomes a challenge when access to new drugs is limited. In Serbia, sunitinib and pazopanib are the only available first-line therapies. The second-line treatment for mRCC has never been and is still not available. We aimed to assess overall survival (OS) in patients with mRCC who received first-line sunitinib or pazopanib when access to second-line treatment was not available. Methods: This retrospective observational study analyzed data from a nationally representative cohort of 759 patients who started on first-line sunitinib or pazopanib between 1 January 2012 and 30 June 2019, in 4 centers in Serbia. The data cut-off date was 31 December 2019. Key eligibility criteria were clear cell RCC histology, measurable metastatic disease, performance status 0 or 1, and the Memorial Sloan Kettering Cancer Center favorable or intermediate prognosis. The primary outcome was OS from the start of first-line treatment to death or data cut-off date. Results: The study population included 759 patients with mRCC who started with first-line sunitinib (n = 673; [88.7%]) or pazopanib (n = 86; [11.3%]). Overall, the mean age was 61.0 ± 9.7 years at treatment baseline, and 547 (72%) were men. mRCC was primarily diagnosed in 230 (30%) patients, and most of them underwent cytoreductive nephrectomy prior to systemic therapy (n = 181 [79%]). Additional treatment of metastases prior to and/or during treatment was used in 169 patients (22.3%). Grade 3 and 4 adverse events occurred in 168 (22.1%) and 47 patients (6.2%), respectively, and treatment was permanently stopped because of toxicity in 41 (6.9%). The OS was calculated from the start of first-line treatment, and the median follow-up was 14 months (range, 0–97). The median OS in the entire cohort was 17 months (95% CI, 14.6–19.4). Conclusions: With only available sunitinib and pazopanib in first-line treatment, modest improvements are seen in the overall survival of patients with mRCC in real world clinical practice. In circumstances of limited availability of cancer medicines, our results can contribute to accelerating patient access to novel cancer therapies that have been shown to prolong survival in mRCC.