Despite recent advances, data on allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients aged ≥70 years remain limited. We identified prognostic factors and developed a risk score to guide transplant eligibility. Using the Japanese Transplant Registry Unified Management Program, we retrospectively analyzed 929 patients aged ≥70 years who underwent their first allo-HSCT for hematologic malignancies between 2000 and 2022. Prognostic factors were identified by multivariate Cox regression to construct a scoring system. The median patient age was 71 years (range, 70-88), with acute myeloid leukemia being the most common disease. The 2-year overall survival (OS) rate was 34.2%. Multivariate analysis identified age ≥75 years, ATL, lymphoma, high disease risk, hematopoietic cell transplant-specific comorbidity index ≥5, and performance status ≥2 as adverse factors. Using the hazard ratio-based scoring system derived from multivariate analysis, patients were stratified into low- (0), intermediate-1- (1), intermediate-2- (2-3), and high-risk (4-5) groups, with 2-year OS rates of 57.1%, 35.0%, 18.3%, and 2.5%, respectively (p < 0.01). We identified prognostic factors and developed a scoring system stratifying survival in patients aged ≥70 years, potentially facilitating the selection of older candidates most likely to benefit from allo-HSCT.
OBJECTIVES:To investigate clinical outcomes, treatment, and survival rates of men aged ≥75 years with prostate cancer in Japan. PATIENTS AND METHODS:The study used data from the Prostate Cancer Research International: Active Surveillance (PRIAS)-JAPAN, a nationwide, multicentre prospective cohort study of men with clinically localised prostate cancer managed with active surveillance (AS). The original eligibility criteria were clinical stage T1c-T2 disease, prostate-specific antigen (PSA) level ≤10 ng/mL, PSA density (PSAD) <0.20 ng/mL/mL, and Gleason Score ≤3 + 3 with two or fewer positive biopsy cores. In 2021, magnetic resonance imaging use expanded eligibility to include patients with a PSA level ≤20 ng/mL, PSAD <0.25 ng/mL/mL, and Gleason Score ≤3 + 4 with <50% of biopsy cores positive. PSA was monitored every 3-6 months, and biopsies were scheduled at 1, 4, 7, and 10 years, and every 5 years thereafter. The outcomes in those aged ≥75 years (older group) were compared with those aged <75 years (younger group). RESULTS:Of the 1274 eligible patients enrolled by 29 February 2024, 231 were in the older group and 1043 were in the younger group. In the older group, the median age at enrolment was 77 years. At diagnosis, patients in the older group had significantly larger prostate volumes, higher proportion of Gleason Score 3 + 4, and more T2 disease than those in the younger group. The protocol biopsy acceptance rate decreased over time (first: 82.9%, second: 63.6%, third: 42.2%, fourth: 22.4%), with no significant difference between age groups. The 10-year AS persistence rate in the older group was 8.8%. The overall survival was significantly lower in the older group than in the younger group (hazard ratio: 0.32, 95% confidence interval 0.14-0.74); however, the 10-year metastasis-free survival and cancer-specific survival rates in the older group were both 100%. CONCLUSION:In some patients aged ≥75 years an observation-focused management approach may be appropriate, in which AS is initiated as a structured monitoring phase with planned de-intensification and transition to watchful waiting, to prevent overtreatment while maintaining excellent cancer-specific outcomes.
BACKGROUND/OBJECTIVES:The multicenter randomized trial JCOG0401 showed that initial salvage radiotherapy (SRT) before salvage hormonal therapy (SHT) significantly prolonged time to treatment failure (TTF) compared with SHT alone. This central pathology analysis aimed to explore pathological features potentially associated with reduced relative benefit from SRT, while distinguishing prognostic from predictive effects. METHODS:We re-analyzed 167 patients from JCOG0401 (SHT: 81, SRT ± SHT: 86). Prostatectomy specimens were re-evaluated, focusing on tertiary Gleason pattern (GP) 5 and intraductal carcinoma of the prostate (IDC-P). Cox proportional hazards models assessed exploratory interaction effects between pathological features and the treatment effect of bicalutamide on TTF. Pathological subgroups in which SRT failed to improve TTF over SHT alone were defined as having reduced benefit from SRT. RESULTS:Adverse pathological features associated with shorter TTF with limited SRT included Gleason score (≥8), GP5, tertiary GP5, IDC-P, positive surgical margins, lymphovascular invasion, and advanced pathological T stage. Exploratory Interaction analyses suggested that IDC-P and tertiary GP5 may be associated with reduced relative benefit from SRT. Among patients without IDC-P, SRT significantly improved TTF (HR 0.330, 95%CI 0.161-0.673), whereas no significant benefit was observed in those with IDC-P (HR: 0.771, 95% CI: 0.446-1.332). Similarly, the absence of tertiary GP5 was associated with a marked benefit from SRT (HR: 0.099, 95% CI: 0.021-0.466), whereas this effect was not observed with tertiary GP5 (HR: 0.760, 95% CI: 0.400-1.443). CONCLUSIONS:IDC-P and tertiary GP5 may represent pathological features associated with reduced relative benefit from SRT after radical prostatectomy. These findings are exploratory and hypothesis-generating and require prospective validation in independent cohorts. Careful pathological evaluation may help identify patients who could benefit from treatment intensification or alternative postoperative strategies.
Clear cell papillary renal cell tumor (CCPRCT), formerly known as clear cell papillary renal cell carcinoma, is a low-grade renal neoplasm characterized by cytokeratin 7 and cup-like carbonic anhydrase 9 immunopositivity and absence of von Hippel-Lindau ( VHL ) abnormalities. Given the prognostic differences, distinguishing CCPRCT from clear cell renal cell carcinoma (CCRCC) is clinically important. However, some tumors diagnosed morphologically and immunohistochemically as CCPRCT have been found to harbor VHL abnormalities, which complicates clinical management. This study aimed to clarify how clinical, histologic, and immunohistochemical characteristics varied based on VHL status. Among 17 CCPRCTs analyzed, VHL abnormalities were identified in 10 (58.8%) cases, including VHL mutations in 6 cases and 3p loss of heterozygosity in 7 cases. Tumors were stratified into 3 groups based on VHL allele status: 3 cases with biallelic VHL inactivation (CCPRCT-bi VHL ), 7 with monoallelic VHL inactivation (CCPRCT-mono VHL ), and 7 with wild-type VHL (CCPRCT-wt VHL ). We integrated the molecular with morphologic and immunohistochemical findings, and reclassified 17 cases into 5 CCRCCs mimicking CCPRCT, 5 CCPRCTs-mono VHL , and 7 CCPRCTs-wt VHL cases. All tumors exhibited favorable clinical courses, with no instances of metastasis or recurrence. No significant differences in clinical, pathologic, or immunohistochemical features were observed among the 3 groups or between CCRCCs mimicking CCPRCT and CCPRCTs. This study demonstrated that strict morphologic and immunohistochemical criteria can distinguish most CCRCCs mimicking CCPRCT from CCPRCT. The diagnosis of CCPRCT should be expanded to include tumors with monoallelic VHL alteration exhibiting typical morphologic and immunohistochemical features.
BACKGROUND AND OBJECTIVE:Combined pulmonary fibrosis and emphysema (CPFE) is characterized by coexisting upper-zone emphysema and lower-zone fibrosis, but standardized diagnostic criteria and clinical outcomes remain poorly defined. This study aimed to evaluate survival, acute exacerbation incidence, and disease progression in CPFE patients using international classification criteria with visual assessment of emphysema extent. METHODS:This multicentre prospective cohort study at 29 Japanese hospitals enrolled 1016 patients with idiopathic interstitial pneumonias (IIPs) or chronic obstructive pulmonary disease (COPD) between 2013 and 2016. CPFE was defined as ≥ 5% emphysema determined by visual assessment of CT scans for IIP patients, according to international classification criteria. Patients were followed for 5 years. RESULTS:Among 528 IIP patients, 92 (17.4%) had CPFE. CPFE patients showed a significantly worse 5-year survival compared with non-CPFE IIP patients (51.4% vs. 63.1%, p = 0.026) and COPD patients (51.4% vs. 84.0%, p < 0.001). After adjustment for covariates including IIP subtype, CPFE remained independently associated with increased mortality among IIP patients (HR of 1.85 [95% CI, 1.27-2.69], p < 0.001). CPFE patients also had a significantly higher acute exacerbation rate than did non-CPFE IIP patients (p < 0.001). The prognostic impact of CPFE was most pronounced in patients with idiopathic pulmonary fibrosis (IPF), with CPFE/IPF patients showing the worst outcomes. CONCLUSION:Visual assessment with a ≥ 5% emphysema threshold effectively identified CPFE patients with a distinct clinical phenotype characterized by poor survival and an increased acute exacerbation incidence. These findings validate international classification criteria and emphasize the need for enhanced surveillance and tailored management strategies for this high-risk population.
