Treatment patterns and prognosis in patients with Bacillus Calmette-Guérin-exposed high-risk non-muscle invasive bladder cancer: a real-world data analysis.

PURPOSE: The International Bladder Cancer Group designated the subgroup that is resistant to Bacillus Calmette-Guérin (BCG) but does not meet the criteria for BCG-unresponsive NMIBC as "BCG-exposed high-risk NMIBC" to guide optimal trial design. We aimed to investigate the treatment patterns and prognoses of patients with BCG-exposed NMIBC. METHODS: We conducted a retrospective chart review of 3283 patients who received intravesical BCG therapy for NMIBC at 14 participating institutions between January 2000 and December 2019. Patients meeting the criteria for BCG-exposed and BCG-unresponsive NMIBC, as defined by the Food and Drug Administration and International Bladder Cancer Group, were selected. To compare treatment patterns and outcomes, high-risk recurrence occurring more than 24 months after the last dose of BCG was defined as "BCG-treated NMIBC." In addition, we compared prognoses between BCG rechallenge and early cystectomy in patients with BCG-exposed NMIBC. RESULTS: Of 3283 patients, 108 (3.3%), 150 (4.6%), and 391 (11.9%) were classified as having BCG-exposed, unresponsive, and treated NMIBC, respectively. BCG-exposed NMIBC demonstrated intermediate survival curves for intravesical recurrence-free and progression-free survival, falling between those of BCG-unresponsive and treated NMIBC. Among patients with BCG-exposed NMIBC, 48 (44.4%) received BCG rechallenge, which was the most commonly performed treatment, and 19 (17.6%) underwent early cystectomy. No significant differences were observed between BCG rechallenge and early cystectomy in patients with BCG-exposed NMIBC. CONCLUSIONS: The newly proposed definition of BCG-exposed NMIBC may serve as a valuable disease subgroup for distinguishing significant gray areas, except in cases of BCG-unresponsive NMIBC.

Prognostication in Lymph Node-Positive Prostate Cancer with No PSA Persistence After Radical Prostatectomy.

BACKGROUND: This study aimed to create a prognostic model to predict disease recurrence among patients with lymph node involvement but no prostate-specific antigen (PSA) persistence and to explore its clinical utility. METHODS: The study analyzed patients with lymph node involvement after pelvic lymph node dissection with radical prostatectomy in whom no PSA persistence was observed between 2006 and 2019 at 33 institutions. Prognostic factors for recurrence-free survival (RFS) were analyzed by the Cox proportional hazards model. RESULTS: Among 231 patients, 127 experienced disease recurrence. The factors prognostic for RFS were PSA level at diagnosis (≥ 20 vs. < 20 ng/mL: hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.09-2.52; P = 0.017), International Society of Urological Pathology grade group at radical prostatectomy (RP) specimen (group ≥ 4 vs. ≤ 3: HR, 1.63; 95% CI 1.12-2.37; P = 0.010), pathologic T-stage (pT3b/4 vs. pT2/3a: HR, 1.70; 95% CI 1.20-2.42; P = 0.0031), and surgical margin status (positive vs. negative: HR, 1.60; 95% CI 1.13-2.28; P = 0.0086). The prognostic model using four parameters were associated with RFS and metastasis-free survival. CONCLUSION: The prognostic model in combination with postoperative PSA value and number of lymph nodes is clinically useful for discussing treatment choice with patients.

Atmospheric formaldehyde production on early Mars leading to a potential formation of bio-important molecules.

Formaldehyde (H2CO) is a critical precursor for the abiotic formation of biomolecules, including amino acids and sugars, which are the building blocks of proteins and RNA. Geomorphological and geochemical evidence on Mars indicates a temperate environment compatible with the existence of surface liquid water during its early history at 3.8-3.6 billion years ago (Ga), which was maintained by the warming effect of reducing gases, such as H2. However, it remains uncertain whether such a temperate and weakly reducing surface environment on early Mars was suitable for producing H2CO. In this study, we investigated the atmospheric production of H2CO on early Mars using a 1-D photochemical model assuming a thick CO2-dominated atmosphere with H2 and CO. Our results show that a continuous supply of atmospheric H2CO can be used to form various organic compounds, including amino acids and sugars. This could be a possible origin for the organic matter observed on the Martian surface. Given the previously reported conversion rate from H2CO into ribose, the calculated H2CO deposition flux suggests a continuous supply of bio-important sugars on early Mars, particularly during the Noachian and early Hesperian periods.

Use of the anterior prostatic urethral mucosa preservation technique during holmium laser enucleation of the prostate can reduce postoperative stress urinary incontinence.

INTRODUCTION: Holmium laser enucleation of the prostate (HoLEP) is an effective and safe surgery for patients with benign prostatic hyperplasia. However, some patients exhibit postoperative urinary incontinence. Here, we compared surgical outcomes and incidence of stress urinary incontinence between HoLEP with and without anterior prostatic urethral mucosa preservation (APUMP). METHODS: All patients in this study underwent HoLEP with APUMP technique (APUMP group) and without APUMP technique (no-APUMP group). Enucleation weight, enucleation time, max flow rate increase at 3 months, and urinary incontinence rates immediately after catheter removal and at 1 month after surgery were compared between the groups. RESULTS: In the APUMP (n = 340) and no-APUMP (n = 75) groups, the median enucleation weights were 34.5 and 35.0 g, respectively (p = .982). The corresponding median enucleation times were 33.0 and 46.5 min (p < .01), and median max flow rate increases at 1 month were 10.5 and 9.9 mL/s (p = .89). The urinary incontinence rates immediately after catheter removal were 4.1% and 14.7% (p < .01), and were 3.8% and 12.0% (p < .01) at 1 month after surgery. CONCLUSION: HoLEP using the APUMP technique could be performed with a shorter operative time while maintaining efficacy. The incidence of postoperative urinary incontinence could be decreased by APUMP, indicating that such preservation facilitates the maintenance of urinary continence after surgery.

GnRH antagonist monotherapy versus a GnRH agonist plus bicalutamide for advanced hormone-sensitive prostate cancer; KYUCOG-1401.

OBJECTIVES: To compare the effectiveness and safety of gonadotropin-releasing hormone (GnRH) antagonist monotherapy to combined androgen blockade (CAB) with a GnRH agonist and bicalutamide in patients with advanced hormone-sensitive prostate cancer (HSPC). METHODS: The study was conducted as KYUCOG-1401 trial (UMIN000014243) and enrolled 200 patients who were randomly assigned to either group A (GnRH antagonist monotherapy followed by the addition of bicalutamide) or group B (CAB by a GnRH agonist and bicalutamide). The primary endpoint was PSA progression-free survival. The secondary endpoints were the time to CAB treatment failure, radiographic progression-free survival, overall survival, changes in serum parameters, including PSA, hormones, and bone and lipid metabolic markers, and adverse events. RESULTS: PSA progression-free survival was significantly longer in group B (hazard ratio [HR], 95% confidence interval [CI]; 1.40, 1.01-1.95, p = 0.041). The time to CAB treatment failure was slightly longer in group A (HR, 95% CI; 0.80, 0.59-1.08, p = 0.146). No significant differences were observed in radiographic progression-free survival or overall survival. The percentage of patients with serum testosterone that did not reach the castration level was higher at 60 weeks (p = 0.046) in group A. No significant differences were noted in the serum levels of bone metabolic or lipid markers between the two groups. An injection site reaction was more frequent in group A. CONCLUSIONS: The present results support the potential of CAB using a GnRH agonist and bicalutamide as a more effective treatment for advanced HSPC than GnRH antagonist monotherapy.

Paradoxical Expression of R-10G-reactive Antigen in Human Testicular Embryonal Carcinoma.

Thus far, several monoclonal antibodies directed against cell-surface carbohydrate antigens have been generated. Among them, R-10G reportedly reacts selectively with human embryonic stem and induced pluripotent stem cells, but not with embryonal carcinoma (EC) cells. However, EC cells derived from patients' EC tumors may exhibit varying levels of R-10G-reactive antigen expression. Thus, we asked whether human EC tissues or germ cell tumor (GCT) tissues other than EC express R-10G-reactive antigen. To do so, we quantitatively analyzed R-10G-reactive antigen expression in 83 testicular GCT surgical specimens containing a total of 125 various GCT components. Accordingly, in all EC components examined, the EC cell plasma membrane was immunolabeled with R-10G, while most seminoma components were R-10G-negative. In non-seminomatous GCT (NSGCT) other than EC (non-EC NSGCT), R-10G-reactive antigen expression was variable, but signal distribution was focal, and the average intensity was weaker than that seen in EC. The percentages of R-10G-positive cells in these three groups varied with high statistical significance (p<0.001 for all combinations). These findings indicate that the R-10G-reactive antigen is preferentially expressed in human testicular EC tissues and, thus, could be used as a diagnostic marker for this malignancy.

Increasing age predicts adverse pathology including intraductal carcinoma of the prostate and cribriform patterns in deferred radical prostatectomy after upfront active surveillance for Gleason grade group 1 prostate cancer: analysis of prospective observational study cohort.

BACKGROUND: In men undergoing upfront active surveillance, predictors of adverse pathology in radical prostatectomy specimens, including intraductal carcinoma of the prostate and cribriform patterns, remain unknown. Therefore, we aimed to examine whether adverse pathology in radical prostatectomy specimens could be predicted using preoperative patient characteristics. METHODS: We re-reviewed available radical prostatectomy specimens from 1035 men prospectively enrolled in the PRIAS-JAPAN cohort between January 2010 and September 2020. We defined adverse pathology on radical prostatectomy specimens as Gleason grade group ≥3, pT stage ≥3, pN positivity or the presence of intraductal carcinoma of the prostate or cribriform patterns. We also examined the predictive factors associated with adverse pathology. RESULTS: All men analyzed had Gleason grade group 1 specimens at active surveillance enrolment. The incidence of adverse pathologies was 48.9% (with intraductal carcinoma of the prostate or cribriform patterns, 33.6%; without them, 15.3%). The addition of intraductal carcinoma of the prostate or cribriform patterns to the definition of adverse pathology increased the incidence by 10.9%. Patients showing adverse pathology with intraductal carcinoma of the prostate or cribriform patterns had lower biochemical recurrence-free survival (log-rank P = 0.0166). Increasing age at active surveillance enrolment and before radical prostatectomy was the only predictive factor for adverse pathology (odds ratio: 1.1, 95% confidence interval: 1.02-1.19, P = 0.0178; odds ratio: 1.12, 95% confidence interval: 1.02-1.22, P = 0.0126). CONCLUSIONS: Increasing age could be a predictive factor for adverse pathology. Our findings suggest that older men could potentially derive advantages from adhering to the examination schedule in active surveillance.

Genome-wide association studies in advanced prostate cancer: KYUCOG-1401-A study.

Androgen-deprivation therapy (ADT) has been widely used for the treatment of advanced prostate cancer. However, prognosis and adverse events (AEs) vary among patients. This study aimed to identify genetic markers able to predict the outcome of ADT. Japanese patients treated with primary ADT for advanced prostate cancer in the KYUCOG-1401 trial were enrolled as a development set. A distinct population of advanced prostate cancer cases treated with ADT was included as a validation set. Single-nucleotide polymorphisms (SNPs) associated with radiographic progression-free survival (rPFS) at 1 year and AEs including de novo diabetes mellitus (DM), arthralgia, and de novo dyslipidemia were identified in the development set by a genome-wide association study (GWAS). The SNPs associated with rPFS in the development study were then genotyped in the validation set. GWAS followed by validation identified SNPs (rs76237622 in PRR27 and rs117573572 in MTAP) that were associated with overall survival (OS) in ADT. A genetic prognostic model using these SNPs showed excellent predictive efficacy for PFS and OS in ADT. In addition, GWAS showed that several SNPs were associated with de novo DM, arthralgia, and de novo dyslipidemia in ADT. This study identified novel multiple SNPs that correlated with outcomes in ADT. Future studies on correlations affecting the therapeutic efficacy of ADT-based combination therapies would make a valuable contribution to the development of personalized medicine.

Identification of the α2 chain of interleukin-13 receptor as a potential biomarker for predicting castration resistance of prostate cancer using patient-derived xenograft models.

BACKGROUND: Several treatment strategies use upfront chemotherapy or androgen receptor axis-targeting therapies for metastatic prostate cancer. However, there are no useful biomarkers for selecting appropriate patients who urgently require these treatments. METHODS: Novel patient-derived xenograft (PDX) castration-sensitive and -resistant models were established and gene expression patterns were comprehensively compared. The function of a gene highly expressed in the castration-resistant models was evaluated by its overexpression in LNCaP prostate cancer cells. Protein expression in the tumors and serum of patients was examined by immunohistochemistry and ELISA, and correlations with castration resistance were analyzed. RESULTS: Expression of the α2 chain of interleukin-13 receptor (IL13Rα2) was higher in castration-resistant PDX tumors. LNCaP cells overexpressing IL13Rα2 acquired castration resistance in vitro and in vivo. In tissue samples, IL13Rα2 expression levels were significantly associated with castration-resistant progression (p < 0.05). In serum samples, IL13Rα2 levels could be measured in 5 of 28 (18%) castration-resistant prostate cancer patients. CONCLUSION: IL13Rα2 was highly expressed in castration-resistant prostate cancer PDX models and was associated with the castration resistance of prostate cancer cells. It might be a potential tissue and serum biomarker for predicting castration resistance in prostate cancer patients.

Genetic variations predicting progression with docetaxel and novel androgen-receptor pathway inhibitors.

Genetic variations represented by single-nucleotide polymorphisms (SNPs) could be helpful for choosing an effective treatment for patients with prostate cancer. This study investigated the prognostic and predictive values of SNPs associated with the prognoses of pharmacotherapy for prostate cancer through their pharmacological mechanisms. Patients treated with docetaxel or androgen receptor pathway inhibitors (ARPIs), such as abiraterone and enzalutamide, for castration-resistant prostate cancer were included. The SNPs of interest were genotyped for target regions. The prognostic and predictive values of the SNPs for time to progression (TTP) were examined using the Cox hazard proportional model and interaction test, respectively. Rs1045642 in ABCB1, rs1047303 in HSD3B1, rs1856888 in HSD3B1, rs523349 in SRD5A2, and rs34550074 in SLCO2A1 were differentially associated with TTP between docetaxel chemotherapy and ARPI treatment. In addition to rs4775936 in CYP19A1, rs1128503 in ABCB1 and rs1077858 in SLCO2B1 might be differentially associated with TTP between abiraterone and enzalutamide treatments. Genetic predictive models using these SNPs showed a differential prognosis for treatments. This study identified SNPs that could predict progression as well as genetic models that could predict progression when patients were treated with docetaxel versus ARPI and abiraterone versus enzalutamide. The use of genetic predictive models is expected to be beneficial in selecting the appropriate treatment for the individual patient.

Comparison of Safety and Efficacy in Endoscopic Combined Intrarenal Surgery Performed in the Lateral Decubitus and Galdakao-modified Supine Valdivia Positions.

OBJECTIVE: To examine the safety and efficacy of Endoscopic combined intrarenal surgery (ECIRS) between the lateral decubitus (LD) and Galdakao-modified supine Valdivia (GMSV) position. METHODS: We retrospectively reviewed the records of 226 patients with renal stones who underwent ECIRS in the LD and GMSV positions between 2018 and 2022. Surgeries early in the study period were mainly performed in the GMSV position, while later surgeries were mainly performed in the LD position. RESULTS: The number of patients in the LD and GMSV groups was 119 and 107, respectively. The proportion of patients who had no residual stone fragments >2 mm detected on radiography the day after surgery did not significantly differ between the LD group (91.6%) and the GMSV group (97.2%). Operation time was significantly shorter in the LD group (72 vs 81 minutes; P = .02). Total fluoroscopy time was significantly shorter in the LD group (92 vs 189 seconds; P<.001). Complication rates did not significantly differ between the groups. Among the variables analyzed, the patient position was independently impact on the fluoroscopy time (OR 0.309; 95% CI, 0.167-0.571; P<.001). CONCLUSION: ECIRS in the LD position is safe and effective and associated with shorter fluoroscopy than the GSMV position.

The efficacy of sequential therapy with docetaxel and cabazitaxel for castration-resistant prostate cancer: A retrospective multi-institutional study in Japan.

OBJECTIVE: This study investigated the efficacy of docetaxel (DOC) and cabazitaxel (CBZ) and examined the factors associated with the prognosis of patients with castration-resistant prostate cancer (CRPC) receiving DOC-CBZ sequential treatment in Japanese real-world data. METHODS: We retrospectively evaluated data for 146 patients who received DOC followed by CBZ. The correlations of prostate specific antigen (PSA) decrease rate and time to progression between DOC and CBZ treatment were examined. Combined progression-free survival (PFS) of DOC-CBZ and overall survival (OS) from the initiation of DOC and the diagnosis of CRPC were evaluated and compared between patients with high and low PSA levels at the start of DOC and CBZ treatment. RESULTS: No correlations of PSA decrease rate and time to progression were observed between DOC and CBZ. The patients for whom DOC was started in higher PSA levels had significantly shorter combined PFS (p = 0.003) and OS from the initiation of DOC (p = 0.002). In patients who started DOC at high PSA levels, those who switched to CBZ at low PSA levels had longer OS than those who switched at high PSA levels (p = 0.048). The OS from CRPC of patients who started DOC at low PSA levels was significantly longer than those that started at high PSA levels (p = 0.030). CONCLUSIONS: For patients for whom DOC was not effective, sequential CBZ might have change to be effective. The PSA levels at the start of DOC and CBZ might be a potential prognostic biomarker.

Efficacy and Safety of Radium-223 for Castration-resistant Prostate Cancer With Bone Metastasis Before and After Docetaxel.

BACKGROUND/AIM: Radium-223 (Ra-223) therapy provides a survival benefit for castration-resistant prostate cancer (CRPC) patients with bone metastasis. The optimal timing of using Ra-223 has not been determined. We evaluated the efficacy and safety of Ra-223 before and after docetaxel (DOC) therapy. PATIENTS AND METHODS: We retrospectively reviewed 36 CRPC patients with bone metastasis who were treated with Ra-223 in our institution and satellite hospitals. Ra-223 was used before DOC (pre-DOC group) in 17 patients (47%) and after DOC (post-DOC group) in 19 patients (53%). The treatment completion rate of 6 cycles, progression-free survival (PFS), cause-specific survival (CSS) and occurrence rate of adverse events were compared between the groups. RESULTS: The median follow-up duration was 45 months. In the pre-DOC compared with the post-DOC group, treatment completion rate was significantly higher (94% vs. 52%, p<0.01), PFS was significantly longer (median: 8 vs. 5 months, p=0.024) and CSS was significantly longer (median: 32 vs. 15 months, p=0.028). The difference in CSS was significant in multivariate analysis. In the pre-DOC compared with the post-DOC group, the occurrence rate of grade ≥3 adverse events tended to be lower (6% vs. 36%, p=0.322), and the CSS tended to be longer (median: not reached vs. 45 months, p=0.208). CONCLUSION: Ra-223 could be used more safely and more effectively for CRPC patients with bone metastasis before than after DOC therapy.

Prognostic significance of pathogenic variants in BRCA1, BRCA2, ATM and PALB2 genes in men undergoing hormonal therapy for advanced prostate cancer.

BACKGROUND: The prognostic significance of germline variants in homologous recombination repair genes in advanced prostate cancer (PCa), especially with regard to hormonal therapy, remains controversial. METHODS: Germline DNA from 549 Japanese men with metastatic and/or castration-resistant PCa was sequenced for 27 cancer-predisposing genes. The associations between pathogenic variants and clinical outcomes were examined. Further, for comparison, DNA from prostate biopsy tissue samples from 80 independent patients with metastatic PCa were analysed. RESULTS: Forty-four (8%) patients carried germline pathogenic variants in one of the analysed genes. BRCA2 was most frequently altered (n = 19), followed by HOXB13 (n = 9), PALB2 (n = 5) and ATM (n = 5). Further, the BRCA1, BRCA2, PALB2 and ATM variants showed significant association with a short time to castration resistance and overall survival (hazard ratio = 1.99 and 2.36; 95% CI, 1.15-3.44 and 1.23-4.51, respectively), independent of other clinical variables. Based on log-rank tests, the time to castration resistance was also significantly short in patients with BRCA1, BRCA2, PALB2 or ATM somatic mutations and TP53 mutations. CONCLUSIONS: Germline variants in BRCA1, BRCA2, PALB2 or ATM are independent prognostic factors of the short duration of response to hormonal therapy in advanced PCa.

Serum IgG4 Concentration Is a Potential Predictive Biomarker in Glucocorticoid Treatment for Idiopathic Retroperitoneal Fibrosis.

OBJECTIVES: To evaluate the management and outcome of idiopathic retroperitoneal fibrosis (iRPF) in Japan, and to identify its clinical biomarker. METHODS: We retrospectively analyzed 129 patients with iRPF treated between January 2008 and May 2018 at 12 university and related hospitals. Patients treated with glucocorticoid were analyzed to identify a predictive biomarker. These patients were classified into three groups according to overall effectiveness (no change: NC, complete response: CR, and partial response groups: PR), and each parameter was compared statistically. RESULTS: Male-female ratio was 5:1, and median age at diagnosis was 69 (33-86) years. Smoking history was reported in 59.6% of the patients. As treatment, 95 patients received glucocorticoid therapy with an overall response rate of 84%. As a result, serum concentration of IgG4 was significantly decreased in NC group compared with the other two groups (56.6 mg/dL vs. 255 mg/dL, 206 mg/dL, p = 0.0059 and 0.0078). ROC analysis was performed between the nonresponder (NC) and responder groups (CR + PR) to identify the cut-off value of serum IgG4 as a predictive marker. As a result, AUC of 0.793 was confirmed. CONCLUSIONS: Pre-treatment serum IgG4 concentration may have potential as a predictive biomarker of steroid treatment.

Cancer-specific and net overall survival in older patients with de novo metastatic prostate cancer initially treated with androgen deprivation therapy.

OBJECTIVE: This study aimed to assess survival outcomes in older patients with de novo metastatic prostate cancer who initially received androgen deprivation therapy. METHODS: The retrospective multicenter study included 2784 men with metastatic prostate cancer who were treated with androgen deprivation therapy between 2008 and 2017. Patients were classified into <75, 75-79, and ≥80 age groups. Propensity score matching was conducted to assess the cancer-specific survival of the groups. The 5-year net overall survival of each group was derived to evaluate relative survival compared with the general population using the Pohar-Perme estimator and the 2019 Japan Life Table. RESULTS: During the follow-up (median, 34 months), 1014 patients died, of which 807 died from metastatic prostate cancer progression. Compared with the <75 group, the cancer-specific survival of the 75-79 group was similar (hazard ratio 1.07; 95% confidence interval 0.84-1.37; P = 0.580), whereas that of the ≥80 group was significantly worse (hazard ratio 1.41; 95% confidence interval 1.10-1.80; P = 0.006). The 5-year net overall survival of the <75, 75-79, and ≥80 age groups were 0.678, 0761, and 0.718, respectively. The 5-year net overall survival of patients aged ≥80 years with low- and high-volume disease were 0.893 and 0.586, respectively, which was comparable with those in patients aged <75 years (0.872 and 0.586, respectively). CONCLUSIONS: Older metastatic prostate cancer patients aged ≥80 years had poorer cancer-specific survival compared with younger patients. Conversely, 5-year net overall survival in older patients aged ≥80 years was comparable with that in younger patients aged <75 years.

Comprehensive genomics in androgen receptor-dependent castration-resistant prostate cancer identifies an adaptation pathway mediated by opioid receptor kappa 1.

Castration resistance is a lethal form of treatment failure of prostate cancer (PCa) and is associated with ligand-independent activation of the androgen receptor (AR). It is only partially understood how the AR mediates survival and castration-resistant growth of PCa upon androgen deprivation. We investigated integrative genomics using a patient-derived xenograft model recapitulating acquired, AR-dependent castration-resistant PCa (CRPC). Sequencing of chromatin immunoprecipitation using an anti-AR antibody (AR-ChIP seq) revealed distinct profiles of AR binding site (ARBS) in androgen-dependent and castration-resistant xenograft tumors compared with those previously reported based on human PCa cells or tumor tissues. An integrative genetic analysis identified several AR-target genes associated with CRPC progression including OPRK1, which harbors ARBS and was upregulated upon androgen deprivation. Loss of function of OPRK1 retarded the acquisition of castration resistance and inhibited castration-resistant growth of PCa both in vitro and in vivo. Immunohistochemical analysis showed that expression of OPRK1, a G protein-coupled receptor, was upregulated in human prostate cancer tissues after preoperative androgen derivation or CRPC progression. These data suggest that OPRK1 is involved in post-castration survival and cellular adaptation process toward castration-resistant progression of PCa, accelerating the clinical implementation of ORPK1-targeting therapy in the management of this lethal disease.

Radiotherapy plus androgen deprivation therapy for prostate-specific antigen persistence in lymph node-positive prostate cancer.

The treatment for lymph node involvement (LNI) after radical prostatectomy (RP) has not been established. This study aimed to reveal the outcomes of various management strategies among patients with LNI after RP. Retrospectively, 561 patients with LNI after pelvic lymph node dissection (PLND) with RP treated between 2006 and 2019 at 33 institutions participating in the Japanese Urological Oncology Group were investigated. Metastasis-free survival (MFS) was the primary outcome. Patients were stratified by prostate-specific antigen (PSA) persistence after RP. Cox regression models were used to analyze the relationships between clinicopathological characteristics and survival. Survival analyses were conducted using the Kaplan-Meier method and log-rank test with or without propensity score matching. Prognoses, including MFS and overall survival, were prominently inferior among patients with persistent PSA compared with those without persistent PSA. In multivariate analysis, androgen deprivation therapy (ADT) plus radiotherapy (RT) was associated with better MFS than ADT alone among patients with persistent PSA (hazard ratio = 0.37; 95% confidence interval = 0.15-0.93; p = 0.034). Similarly, MFS and overall survival were significantly better for ADT plus RT than for ADT alone among patients with persistent PSA after propensity score matching. This study indicated that PSA persistence in LNI prostate cancer increased the risk of poor prognoses, and intensive treatment featuring the addition of RT to ADT might improve survival.