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We investigated trends in the use of perioperative therapy and the efficacy of adjuvant immunotherapy on the prognosis of patients with muscle-invasive urothelial carcinoma (MIUC). The usage and trends in neoadjuvant and adjuvant therapy were examined, and the efficacy of adjuvant immunotherapy was assessed using propensity score-adjusted Cox multivariate analysis. We investigated 1383 patients with muscle-invasive bladder cancer and 1124 patients with upper tract urothelial carcinoma; 1095 (43.7%) patients received neoadjuvant therapy and 366 (14.6%) patients received adjuvant therapy. Adjuvant therapy usage rate increased from 30.3% before 2022 to 61% after 2022 in patients with pathological high-risk cancer (pT3-4, ypT2-4, or pN+). The adjuvant immunotherapy usage rate increased from 2.8% before 2022 to 67.5% after 2022. Sixty-three (18.9%) of the 334 patients with pathological high-risk cancer who were treated with adjuvant therapy were treated with adjuvant immunotherapy. The propensity score-adjusted Cox multivariate analysis showed that adjuvant immunotherapy significantly improved disease-free survival (Hazard ratios (HR) 0.39, P  < 0.005) and overall survival (HR 0.20, P  < 0.005) compared with conventional adjuvant chemotherapy. In conclusion, the introduction of adjuvant immunotherapy led to the increased use of adjuvant therapy and improved prognoses in patients with MIUC in real-world practice.

Follow-up of clear cell renal cell carcinoma following adjuvant pembrolizumab is a relatively new clinical problem that is influenced by immune pressure and heterogeneous resistance biology. Adjuvant anti-PD-1 treatment has revolutionized postoperative treatment by improving disease-free survival and the overall survival rate, but a significant proportion of patients develop recurrence with unique timing and clinical and molecular patterns, which have important implications. This review attempts to summarize and explain the available data on recurrence phenotypes, including timing, disease burden, and molecular determinants, and then elucidates how these factors influence the choice of subsequent treatment strategies. Early recurrence may suggest primary immune resistance, supporting a mechanism switch towards vascular endothelial growth factor (VEGF)-targeted or hypoxia-inducible factor-2α (HIF-2α)-targeted therapy, although this interpretation remains a hypothesis rather than an established mechanistic truth. Conversely, late recurrence may be associated with residual immunological sensitivity, potentially permitting immune checkpoint inhibitors–tyrosine kinase inhibitors combinations or immunotherapy rechallenge in carefully selected patients. The status of focal therapy in the oligometastatic relapse, emerging treatment trends in the real world, and recommendations provided by the modern global guidelines are addressed. In the setting where there are no prospective trials in the post-adjuvant setting, a biologically informed, mechanism-based approach is required to streamline sequencing strategies in this unique and more frequently observed population of patients.

Backgrounds While adjuvant immunotherapy (AIT) is recommended for non-pathological complete response (non-pCR) patients, its role in ypStage I esophageal cancer (EC) patients with low tumor burden remains unclear. The study aims to evaluate the necessity of AIT for esophageal cancer patients achieving ypStage I following neoadjuvant immunochemotherapy (NICT) and surgery. Methods This retrospective study analyzed 157 ypStage I (ypT0-2N0M0) EC patients treated with NICT followed by surgery in Sun Yat-sen University Cancer Center between 2019 and 2024. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) adjusted for baseline imbalances between the none adjuvant therapy (NAT, n = 121)  group and AIT (n = 36) group. Survival outcomes analyses and Cox regression analyses were performed. Results In the unmatched cohorts, 3-year overall survival (3-y OS) was 93.53% (NAT) versus 87.68% (AIT) ( p  = 0.76), and 3-year disease-free survival (3-y DFS) was 86.38% versus 84.17% ( p  = 0.60). Post-PSM (OS: 91.95% vs. 87.68%, p  = 0.81 and DFS: 88.58% vs. 84.17%, p  = 0.45) and IPTW-adjusted analyses (OS: 93.74% vs. 87.76%, p  = 0.76 and DFS: 87.96% vs. 79.08%, p  = 0.60) confirmed no survival advantage for AIT. Cox regression revealed no significant prognostic value of AIT for OS (unmatched cohorts: HR = 1.29, p  = 0.757; PSM: HR = 1.270, p  = 0.810; and IPTW: HR = 1.760, p  = 0.536) or DFS (unmatched cohorts: HR = 1.320, p  = 0.597; PSM: HR = 1.720, p  = 0.459; and IPTW: HR = 2.230, p  = 0.207). Conclusions Patients with ypStage I EC following NICT and surgery might not benefit from AIT. This study provides a hint for the risk–benefit balance of prolonged immunotherapy exposure in ypStage I patients while preserving clinical efficacy. Further studies are warranted.

Our earlier multicenter randomized controlled trial showed that adjuvant immunotherapy with cytokine-induced killer (CIK) cells resulted in longer recurrence-free survival (RFS) and overall survival (OS) as well in patients who received curative treatment for hepatocellular carcinoma (HCC). In the present study, we determined if the efficacy of CIK cell therapy continued after end of repeated CIK cell injections. We performed a follow-up study of our preceding trial. We included 226 patients: 114 patients in the immunotherapy group (injection of 6.4 × 109 CIK cells, 16 times during 60 weeks) and 112 patients in the control group (no treatment) after potentially curative treatment for HCC. In total, 162 patients (89 of the immunotherapy group and 73 of controls) underwent an extended follow-up for 60 months after randomization of the last patient. The primary endpoint was RFS, and secondary endpoints included OS. During follow-up time of median 68.5 months (interquartile range 45.0–82.2 months), the immunotherapy group continued to show a significantly lower risk of recurrence or death [hazard ratio (HR) 0.67; 95% confidence interval (CI) 0.48–0.94; P = 0.009 by one-sided log-rank test]. At 5 years, RFS rate was 44.8% in the immunotherapy group and 33.1% in the control group. The risk of all-cause death was also lower in the immunotherapy group compared to the control group (HR 0.33; 95% CI 0.15–0.76; P = 0.006). In patients who received curative treatment for HCC, the significant improvement in RFS and OS as a result of adjuvant CIK cell immunotherapy lasted over 5 years without boosting.

Immune checkpoint inhibitors (ICIs) have fundamentally altered the therapeutic paradigm for head and neck squamous cell carcinoma (HNSCC); however, durable clinical benefit remains limited to biologically defined patient populations. These clinical limitations necessitate a shift away from empirical monotherapy toward precision-guided combination strategies that actively reprogram immune resistance. In this review, we integrate contemporary clinical and translational evidence regarding ICI-based combinations with radiotherapy (RT), chemotherapy, and emerging non-cytotoxic sensitization approaches, with particular emphasis on neoadjuvant and perioperative treatment settings. Central to these strategies is the dynamic remodeling of the tumor immune microenvironment (TIME), rather than simple amplification of immune activation. Recent studies demonstrate that immune-sensitizing interventions – including RT-induced immunogenic cell death, innate immune pathway activation, metabolic and microbiome modulation, and bioengineered drug delivery systems—can convert immunologically inert tumors into immune-interrogable tissues by restoring antigen presentation, spatial immune organization, and effector T-cell competence. Concurrently, integrative biomarker frameworks—encompassing PD-L1 expression, tumor mutational burden, tertiary lymphoid structures, tissue-resident memory T cells, and immune spatial organization—are redefining approaches to patient stratification and therapeutic sequencing. Despite compelling mechanistic rationale, clinical translation remains hindered by inadequate biomarker integration, heterogeneous clinical trial design, and discordance between biological endpoints and survival outcomes. Collectively, these advances delineate a transition from empiric combination therapy toward immune-centric precision immuno-oncology in HNSCC, underscoring the necessity for biomarker-driven trial design, longitudinal immune monitoring, and multidisciplinary collaboration to translate mechanistic synergy into durable clinical benefit.

Background Radical or partial nephrectomy followed by adjuvant pembrolizumab is the standard of care for high-risk localized renal cell carcinoma (RCC), yet around 40% of patients relapse within 5 years. We investigated patterns of disease recurrence and the clinical management of RCC patients treated with adjuvant immunotherapy. Materials and methods We collected patients with high-risk RCC who received adjuvant immunotherapy after radical surgery in our Institution. The primary endpoint was the rate and pattern of disease recurrence. Secondary endpoints were disease-free survival (DFS), overall survival (OS), post-progression survival (OS2) and treatments at recurrence. Results From March 2018 to September 2025, 70 patients were included, most received adjuvant pembrolizumab (71%), followed by nivolumab + ipilimumab (16%), and nivolumab monotherapy (13%). 15 patients (21%) experienced recurrence, including 7 (10%) who relapsed on adjuvant treatment. Oligometastatic disease was observed in 10 cases (67%), mainly involving lung (60%), lymph nodes (33%) and renal bed (13%). At recurrence, 9 patients (60%) started first-line therapy, while 5 patients (33%) received loco-regional treatments. After a median follow-up of 30.2 months, 30-month DFS and OS rates were 74% and 94%, respectively, in the overall population. Among patients who progressed, the 24-month OS2 rate was 100% after local therapy alone and 86% with systemic therapy. Conclusions High-risk RCC patients treated with adjuvant immunotherapy remain at considerable risk of relapse, frequently with oligometastatic disease. Excellent post-progression outcomes after loco-regional treatment support a multidisciplinary, metastasis-directed approach to recurrence after adjuvant immunotherapy.

Background Most adjuvant therapies for hepatocellular carcinoma (HCC) have failed except for autologous cytokine-induced killer (CIK) therapy, which prolonged recurrence-free survival (RFS) in a previously reported randomized controlled trial (RCT) and real-world data (RWD). Methods This study aimed to assess the long-term outcomes of adjuvant CIK therapy using both an extended follow-up of the original RCT and a retrospective cohort study. An extended follow-up analysis of the RCT included 226 patients (114 in the CIK group and 112 in the control group). The follow-up duration was extended from 2 to 9 years after the enrollment of the last patient. In parallel, a retrospective RWD study was performed involving 577 patients from two tertiary centers in Korea, including 251 who received adjuvant CIK therapy and 326 controls. Propensity score matching (PSM) was applied to adjust for baseline imbalances. The primary endpoint was RFS in both studies. Results In the RWD study (median follow-up = 57.2 months), the CIK group demonstrated significantly prolonged RFS than controls both before PSM (median = 101.2 versus 64.7 months; HR = 0.69, 95% CI 0.53–0.90, P  = 0.006) and after PSM (median = 101.2 vs. 65.7 months; HR = 0.64, 95% CI 0.45–0.91, P  = 0.01). In the extended follow-up of the RCT (median follow-up = 116.1 months), the CIK group exhibited significantly prolonged RFS (median = 44.0 vs. 30.0 months; hazard ratio [HR] = 0.72, 95% confidence interval [CI] 0.54–0.97, P  = 0.033) compared to the control group. Conclusions Adjuvant CIK cell therapy significantly improved RFS in both a RWD study and a 9-year extended RCT follow-up, supporting its reproducible benefit in reducing recurrence after curative treatment of HCC. These consistent findings provide strong evidence for the clinical utility of CIK therapy as a durable adjuvant immunotherapeutic strategy for HCC.

The role of immunotherapy in the adjuvant setting seems promising in recent years. As per the findings of the CheckMate 577 trial, patients with esophageal cancer (EC) who had neoadjuvant chemoradiation with residual pathologic disease should be considered adjuvant immunotherapy (AIT). However, it is unknown if individuals with esophageal squamous cell carcinoma (ESCC) who have received neoadjuvant immunochemotherapy (NICT) followed by radical surgery also require AIT. A retrospective analysis was performed on the data from patients who underwent NICT and radical surgery for ESCC between 2019 and 2020. To compare disease-free survival (DFS) and overall survival (OS), Kaplan-Meier survival curves were produced. To determine the parameters linked to DFS and OS, a Cox model using hazard ratios (HRs) was completed. Among the 292 eligible patients, 215 cases with a mean age of 63.3 ± 6.8 years, including 190 (88.4%) men and 25 (11.6%) women, were finally recruited. The percentage of R0 resection was 98.3%. After NICT, 65 (30.2%) patients achieved pathological complete response. AIT was given to 78 (36.3%) patients following radical resection. For all patients, the 3-year DFS and OS were 62.3% and 74.0%, respectively. In terms of 3-year DFS (61.5% vs. 62.8%, P=0.984) or OS (76.9% vs. 72.3%, P=0.384), no statistically significant difference was found between patients with and without AIT. AIT significantly improved survival in patients with ypT+N+ (DFS: 23.9% vs. 38.5%, P=0.036; OS: 37.0% vs. 61.5%, P=0.010), but not in those with ypT0N0 or ypT+N0. It was found that AIT was related to both DFS (HR: 0.297; P<0.001) and OS (HR: 0.321; P=0.001) in patients with ypT+N+. In ypT+N+ ESCC patients, AIT after NICT followed by radical surgery reduces the recurrence and death, thereby improving the DFS and OS. Randomized controlled trials ought to be conducted to further assess the results of this retrospective investigation.

The majority of locally advanced esophageal squamous cell carcinoma (ESCC) patients do not achieve a pathological complete response (NPCR) after neoadjuvant chemoimmunotherapy (NCIT), and their prognosis exhibits significant heterogeneity. This study aimed to establish a pathological subtyping system for NPCR patients to guide precision adjuvant therapy. We conducted a retrospective analysis of 243 patients with locally advanced ESCC who underwent NCIT followed by esophagectomy. NPCR patients were categorized into three pathological subtypes based on the anatomical sites of residual disease: T+N+ (residual tumor in both primary site and lymph nodes), T+N0 (residual tumor confined to primary site only), and T0N+ (residual disease in lymph nodes only). Survival outcomes were compared, and the efficacy of adjuvant immunotherapy was evaluated within each subtype. Prognostic nomograms for disease-free survival (DFS) and overall survival (OS) were constructed and validated. Among 176 NPCR patients, the novel subtyping system achieved significant prognostic stratification. The T+N+ subtype demonstrated the poorest survival outcomes, while the T0N+ subtype did not significantly differ from the PCR cohort. Notably, adjuvant immunotherapy provided significant survival benefits exclusively in the T+N0 subtype (DFS: HR = 3.45, 95% CI: 1.17-10.17, P = 0.025; OS: HR = 4.17, 95% CI: 1.07-16.23, P = 0.039), with no significant benefits observed in either the T+N+ or T0N+ subtypes. Based on these findings, we developed and internally validated prognostic nomograms integrating pathological subtype, ypTNM stage, and other key clinicopathological variables, which demonstrated good predictive accuracy (C-index >0.75) for individualized risk assessment. We propose a novel and practical pathological subtyping framework for NPCR ESCC patients that effectively resolves prognostic heterogeneity and identifies, the T+N0 subtype as the primary beneficiary of adjuvant immunotherapy. The developed nomograms provide a user-friendly tool to facilitate personalized postoperative management and adjuvant therapy decisions.

Background: To date, no adjuvant treatment has been shown to have a clear benefit in patients with hepatocellular carcinoma (HCC). In this prospective phase I/IIa study, we evaluated the safety and efficacy of adjuvant dendritic cell (DC) therapy in HCC patients who received primary treatment for HCC. Methods: Twelve HCC patients who had no viable tumour after primary treatments were included. Dendritic cell vaccines pulsed with cytoplasmic transduction peptide-attached alpha-fetoprotein, glypican-3 and melanoma-associated antigen 1 recombinant fusion proteins were injected subcutaneously near to inguinal lymph nodes. Adverse effects, time to progression (TTP), and associated immune responses were evaluated after DC vaccination. Results: Nine of 12 patients had no tumour recurrence up to 24 weeks after DC vaccination. Among a total of 144 adverse events, 129 events (89.6%) were regarded as adverse drug reactions, all of which were grade 1 or 2. The majority of patients showed enhanced anti-tumour immune responses after DC vaccination. Recurrence-free patients exhibited relatively stronger anti-tumour immune responses than patients who developed recurrence after DC vaccination, as evidenced by lymphocyte proliferation and IFN- γ ELISPOT assays. The median time of TTP was 36.6 months in the DC-vaccination group and 11.8 months in the control group (hazard ratio, 0.41; 95% confidence interval, 0.18–0.95; P =0.0031 by log-rank test). Conclusions: Adjuvant DC vaccine for HCC was safe and well tolerated in phase I/IIa study, and preliminary efficacy data are encouraging to warrant further clinical study in patients with HCC after primary treatments.