We evaluated the significance of spread through alveolar space (STAS) as a predictor of cancer recurrence in epidermal growth factor receptor (EGFR)-mutated pathological stage IA lung adenocarcinomas. Between 2011 and 2020, data from 856 patients with surgically resected pathological stage IA EGFR-mutated lung adenocarcinoma were evaluated to investigate the oncological and prognostic roles based on the presence of STAS. The cumulative incidence of recurrence (CIR) was estimated using the Fine-Gray test. Survival outcomes were assessed using Kaplan-Meier analysis and log-rank tests. Seventy patients (8.2%) were STAS-positive, demonstrating a higher proportion of larger tumor size, lymphovascular invasion, nonlepidic predominant lesions, and the Ex19 subtype (P < .001). Postoperative cancer recurrence was significantly higher in the STAS-positive group (total: 18.6% vs. 5.7%, P < .001; locoregional: 10.0% vs. 3.8%, P = .015; distant: 15.7% vs. 3.7%, P < .001). Both CIR and recurrence-free survival (RFS) differed significantly according to the presence of STAS (5y-CIR: 14.4% vs. 4.2%, P < .001; 5y-RFS: 83.2% vs. 91.8%, P = .001). Multivariate analysis revealed that the presence of STAS (P = .028), lymphovascular invasion (P = .020), pathologic tumor size (P = .036), and absence of a lepidic component (P < .001) were independent significant factors for CIR. When combined with STAS, these factors further increased recurrence prediction (STAS and absence of a lepidic component, 5y-CIR: 26.8% vs. 4.0%, P < .001; STAS and larger tumor size, 18.1% vs. 4.3%, P < .001; STAS and lymphovascular invasion, 27.1% vs. 4.5%, P < .001). STAS is an important risk factor for predicting postoperative cancer recurrence in EGFR-mutated pathological stage IA lung adenocarcinomas.

Residual or recurrent esophageal squamous cell carcinoma (ESCC) after definitive chemoradiotherapy (CRT) is a therapeutic challenge. Salvage surgery is invasive, and endoscopic resection is limited by radiation-induced fibrosis. Argon plasma coagulation (APC) and photodynamic therapy (PDT) are less invasive salvage options, however their role in depth-oriented organ-preserving strategies remains unclear. We analyzed 52 consecutive patients with residual or recurrent ycT1-2 ESCC who underwent CRT. APC is indicated for ycT1a lesions, and PDT is indicated for ycT1b-T2 lesions, with flexibility. We evaluated the survival rates, adverse events, and predictors of local failure. Thirteen patients underwent APC, and 39 underwent PDT. The overall local complete response rate was 78.8% (92.3% APC and 74.3% PDT). During a median follow-up of 24.7months (range, 1.9-110.5months), the 2-year overall survival, progression-free survival, disease-specific survival, and esophagectomy-free survival rates were 82.8%, 44.0%, 86.7%, and 75.9%, respectively. Adverse events occurred in 30.8% of APC patients and 41.0% of PDT patients, all of which were manageable without treatment-related mortality. Multivariate analysis identified ycT2 stage (hazard ratio [HR]: 9.61, 95% confidence interval [CI]: 1.04-88.55, P=.04) and tumor location in the upper thoracic esophagus (HR 3.48, 95% CI 1.02-11.85; P=.04) as independent predictors of local failure. A salvage endoscopic strategy applying APC for ycT1a and PDT for ycT1b-T2, with flexibility based on tumor depth, is feasible, safe, and effective. Tailoring treatment to invasion depth may optimize organ preservation and local control in residual or recurrent ESCC after CRT.

The phase III TALAPRO-2 trial showed that talazoparib plus enzalutamide significantly improves radiographic progression-free survival (rPFS) in patients with metastatic castration-resistant prostate cancer. In contrast, the Japanese subgroup (n=116) demonstrated non-significant results with wide confidence intervals, as expected, because of the limited sample size. We attempted to provide complementary insights using Bayesian methods to quantify the probability of treatment benefit. We performed a Bayesian analysis using published data from the TALAPRO-2 trial. Prior distributions were set across four scenarios based on global trial data: neutral prior (no borrowing), conservative borrowing (prior standard deviation [SD]=2×standard error [SE]), moderate borrowing (prior SD=1.5×SE), and strong borrowing (prior SD=SE). The posterior distributions for the Japanese subgroup were derived using normal-normal conjugate updating. The 'treatment effectiveness (hazard ratio [HR] < 1)' probability in Japanese all-comers reached 98% with conservative borrowing and>99% with moderate and strong borrowing. With moderate borrowing, the posterior mean HR was 0.67 (95% credible interval 0.50-0.89). In the homologous recombination repair-deficient subgroup, all borrowing scenarios excluded HR=1.0, with P(HR<1.0) exceeding 99%. Using Bayesian evidence synthesis with prespecified borrowing levels, the Japanese subgroup results were compatible in direction and magnitude with the overall TALAPRO-2 effect. These findings reduce uncertainty around local extrapolation; a dedicated randomized study would be required to establish efficacy independently in Japanese patients.

Patients undergoing curative surgery for upper gastrointestinal (UGI) cancers often experience substantial postoperative weight loss and reduction in muscle mass, one contributing factor being decreased ghrelin secretion following surgery. Anamorelin, a ghrelin receptor agonist, has been shown to improve appetite and increase lean body mass in patients with cancer cachexia; however, its efficacy in the postoperative setting has not been established. The CLEAR-UP study is a multicenter, open-label, randomized controlled trial designed to investigate the clinical effects of anamorelin in patients who have undergone curative resection for gastric or esophageal cancer. A total of 160 patients will be randomly assigned in a 1:1 ratio to receive either anamorelin (100mg orally once daily for 12weeks) or standard postoperative care without pharmacological intervention. Randomization will be stratified by cancer type (gastric vs. esophageal) and baseline body mass index (BMI <18.5 vs. ≥18.5). All patients will be followed for 48weeks. The primary endpoint is the percent change in lean body mass at 12weeks, assessed using multifrequency bioimpedance analysis. Secondary endpoints include changes in body weight, fat mass, muscle, and fat cross-sectional area on CT, muscle strength, appetite, quality of life, hormonal markers, nutritional indicators, and adverse events. This study aims to clarify the potential benefits of anamorelin in mitigating postoperative deterioration of body composition in patients with UGI cancer and to provide essential preliminary data to inform the design of future confirmatory trials.

Radical cystectomy (RC) remains the standard treatment for muscle-invasive bladder cancer (MIBC), but is highly invasive and may cause functional decline, especially among geriatric patients. This study evaluated age-stratified outcomes of RC through a nationwide, multi-institutional cohort in Japan. We analyzed 1867 patients with MIBC who underwent RC at 36 institutions, stratified into five age groups: <60, 60-69, 70-74, 75-79, and≥80years. The baseline characteristics, perioperative factors, and oncological outcomes were compared. Patients aged ≥80years had significantly worse overall survival (OS, P<.001), cancer-specific survival (CSS, P=.006), and disease-free survival (DFS, P=.004) after RC. Although preoperative clinical T stage was comparable (P=.22), patients aged ≥80years less frequently received neoadjuvant chemotherapy (NAC), and more often showed pathological extravesical extension and positive surgical margins (all P<.001). The incidence of grade≥3 complications and 30-day mortality were comparable, whereas 90-day mortality was higher in this group (P=.047). Multivariable Cox analysis confirmed age≥80years as an independent predictor for unfavorable OS (P<.001), CSS (P=.017), and DFS (P=.018). Among patients aged ≥80years, the use of NAC was associated with better OS (P=.033), particularly in those with Eastern Cooperative Oncology Group performance status of 0 (P=.015). Patients aged ≥80years had significantly worse oncological outcomes after RC. NAC may improve OS in selected older patients with good performance status.

Intraductal carcinoma of the prostate (IDC-P) and phosphatase and tensin homolog (PTEN) alteration are established adverse features in prostate cancer. However, their coexistence and prognostic relevance in the era of androgen receptor pathway inhibitor (ARPI) therapy for metastatic castration-sensitive prostate cancer (mCSPC) remain unclear, particularly in Japanese populations. We evaluated the prevalence, concordance, and prognostic significance of IDC-P and PTEN loss in patients with mCSPC treated with ARPI plus androgen deprivation therapy (ADT). We retrospectively analyzed consecutive patients with mCSPC who received ARPI plus ADT between February 2018 and June 2024 across three Japanese institutions. IDC-P was assessed on hematoxylin-eosin-stained biopsy specimens. PTEN loss was defined as ≥90% absence of cytoplasmic staining, consistent with the CAPItello-281 trial criteria. The primary endpoint was castration-resistant prostate cancer-free survival (CRPC-FS). Overall survival was evaluated as a secondary endpoint. Survival outcomes were assessed using Kaplan-Meier analysis and multivariable Cox regression modeling. In total, 121 patients were included. IDC-P was identified in 68.6% of biopsy specimens, and PTEN loss in 15.7%. Patients with IDC-P more frequently presented with CHAARTED high-volume and LATITUDE high-risk disease. During a median follow-up of 36months, 44 patients (36.4%) developed CRPC. IDC-P was independently associated with shorter CRPC-FS [hazard ratio [HR] 2.4, 95% confidence interval (CI) 1.14-5.04; P=.02], whereas PTEN loss was not significantly associated with CRPC-FS or overall survival. Combined assessment of IDC-P and PTEN loss did not demonstrate additive prognostic value. In this multicenter Japanese cohort, IDC-P, but not PTEN loss, independently predicted earlier progression to CRPC in patients with mCSPC treated with ARPI plus ADT. The limited overlap between IDC-P and PTEN loss suggests distinct biological mechanisms in Japanese populations. IDC-P remains a strong morphologic indicator of aggressive disease, whereas PTEN loss may serve as a therapeutic biomarker for phosphoinositide 3-kinase/AKT-targeted strategies.

To evaluate the palliative efficacy of re-irradiation stereotactic body radiotherapy (SBRT) for painful spinal metastases. In this single-centre, single-arm, phase II study, patients with painful spinal metastases (pain score ≥2 on a 0-10 scale) from solid tumours were enrolled. Eligibility criteria included absence of epidural spinal cord compression, and irradiation history (excluding SBRT) with an interval of ≥3months. The prescribed dose was 24Gy in two fractions; the maximum spinal cord dose constraint was 12.2Gy. The primary endpoint was the pain response rate at 6months in evaluable patients. Among 35 spinal lesions in 34 patients registered between July 2019 and June 2024, 11 (31%) lesions were severely painful (score, 8-10), 16 (46%) were radioresistant, and 14 (40%) involved ≥3 consecutive vertebrae. The median prior equivalent dose in 2-Gy fractions (α/β=10) was 33 (range, 23-70) Gy, and median interval between irradiations was 12 (range, 3-114) months. The median follow-up period was 9 (range, 2-51) months. Among evaluable patients, pain response was 84% at 3months and 83% at 6months, whereas complete response (CR) was 48% and 56%, respectively. In the intention-to-treat analysis, pain response was 60% at 3months and 43% at 6months, whereas CR was 34% and 29%, respectively. The 6-month local failure rate was 7%. Two (6%) patients experienced grade 3 toxicities. Re-irradiation SBRT achieved substantial pain relief with acceptable toxicity, warranting larger randomized trials against conventional radiotherapy.

While opioid analgesics are widely used to manage moderate-to-severe cancer-related pain, dosing is mostly based on subjective pain reports rather than objective physiological indicators, potentially contributing to inconsistent dosing and suboptimal pain control. This study investigated whether model-predicted oxycodone serum concentrations could guide opioid dosing and whether wearable-derived heart rate and step count, combined with these predictions, could complement conventional numerical rating scale (NRS) pain assessments. Sixteen patients with advanced genitourinary cancer receiving oxycodone were prospectively monitored. Clinically collected serum concentrations were used to simulate individual pharmacokinetic profiles. Pain intensity was assessed using the NRS, and physiological parameters were recorded using wearable devices. Linear mixed-effects models were constructed to evaluate the associations between simulated serum oxycodone concentrations, NRS, and physiological variables. In the linear mixed-effects model, simulated serum oxycodone concentrations were significantly associated with lower NRS scores (β=-0.26, P=.0177). Although neither heart rate nor step count independently predicted NRS, incorporating heart rate into the model improved the overall fit. Thus, heart rate may capture pain-related physiological responses not fully explained by oxycodone concentration alone, thereby enhancing the explanatory power of the model. Model-based simulated serum oxycodone concentrations may serve as an objective reference for individualized pain assessment and opioid titration. Combining wearable-derived physiological signals, particularly heart rate, with model-predicted oxycodone concentrations may further improve the precision and adaptability of pain management in palliative care.