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.

Associations between early changes in the neutrophil-to-lymphocyte ratio after radical nephroureterectomy and treatment outcomes.

OBJECTIVES: This study explored the impacts of peri-operative changes in the neutrophil-to-lymphocyte ratio (NLR) on the survival rate after radical nephroureterectomy. METHODS: This retrospective analysis included a multicentric cohort of patients diagnosed with upper tract urothelial carcinoma (UTUC) who had undergone radical nephroureterectomy from 2012 to 2021. We assessed the preoperative NLR, postoperative NLR, delta-NLR (difference between postoperative and preoperative NLRs), and NLR change (ratio of postoperative to preoperative NLR). Additionally, patients were categorized according to increases in their preoperative and/or postoperative NLRs. Associations of survival with peri-operative changes in the NLR were investigated using Cox multivariate regression models. RESULTS: A total of 488 patients were included in the study, with a median age of 73 years. Among the patients, 105 (21.5%) exhibited elevated preoperative and postoperative NLRs, 88 (18.0%) exhibited elevated preoperative NLR only, 53 (10.9%) exhibited elevated postoperative NLR only, and 242 (49.6%) exhibited normal NLRs. Multivariate analysis indicated significant negative correlations between both preoperative and postoperative increased NLRs and oncological outcomes, including nonurothelial tract recurrence-free survival and cancer-specific survival (hazard ratio [HR]: 1.65, P = 0.017; HR: 2.12, P = 0.014, respectively). CONCLUSION: This is the first study to evaluate the association between peri-operative changes in the NLR and the outcomes of patients with UTUC who underwent radical nephroureterectomy. Patients with elevated NLRs at both time points experienced considerably worse outcomes. Further research should explore whether increases in the NLR during long-term follow-up could indicate impending disease recurrence.

Real-world evidence of triplet therapy efficacy in patients with metastatic castration-sensitive prostate cancer: a Japanese multicenter study.

BACKGROUND: Two randomized trials demonstrated that the survival benefits afforded by triplet therapy were greater than those of doublet therapy, thus changing the treatment paradigm for metastatic castration-sensitive prostate cancer (mCSPC). This is the first study to assess the real-world use, performance, and safety of triplet therapy in Japanese patients. METHODS: This retrospective multicenter study included 45 consecutive mCSPC patients who received triplet therapy composed of androgen deprivation therapy (ADT), docetaxel, and darolutamide between January 2023 and June 2024. Baseline patient characteristics and their clinical parameters during triplet therapy were collected. Adverse events (AEs) were graded using Common Terminology Criteria for Adverse Events version 5.0, and imaging responses were evaluated following the RECIST criteria. The prostate-specific antigen (PSA) nadir was defined as the lowest PSA value during follow-up, and the PSA decrease was the initial PSA value minus the PSA nadir. RESULTS: The median patient age was 70 years and the median follow-up duration was 10 months. High-volume disease was present in 82.2% of patients. Concurrent administration of docetaxel and darolutamide was scheduled for 22.2% of cases. The incidence of any AE was 86.7%, with 55.5% of patients experiencing grade 3-4 AEs. Neutropenia was common, but prophylactic granulocyte colony-stimulating factor (G-CSF) significantly reduced the incidence of neutropenia of grade 3 or higher. Febrile neutropenia occurred in four patients (8.9%); these patients had not received prophylactic G-CSF. A decline in PSA of 90% was observed in 95.6% of patients, and an imaging response was seen in 97.8%. CONCLUSIONS: Triplet therapy with ADT, darolutamide, and docetaxel was highly efficacious and tolerable in Japanese mCSPC patients, particularly those with high-volume disease. Prophylactic G-CSF prescription is crucial to manage neutropenia effectively. Further studies with longer follow-ups are needed to confirm these findings and explore the long-term outcomes.

Real-world outcomes of adjuvant immunotherapy candidates with upper tract urothelial carcinoma: results of a multicenter cohort study.

BACKGROUND: Recent clinical trials have reported improved disease-free survival rates of patients with stage pT3-4/ypT2-4 or pN + upper tract urothelial carcinoma (UTUC) on adjuvant nivolumab therapy. However, the appropriateness of the patient selection criteria used in clinical practice remains uncertain. METHODS: We retrospectively analyzed 895 patients who underwent nephroureterectomy to treat UTUC. The patients were divided into two groups: grade pT3-4 and/or pN + without neoadjuvant chemotherapy (NAC) or grade ypT2-4 and/or ypN + on NAC (adjuvant immunotherapy candidates) and others (not candidates for adjuvant immunotherapy). Kaplan-Meier curves were drawn to assess the oncological outcomes, including recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Cox proportional hazards models were used to identify significant prognostic factors for oncological outcomes. RESULTS: The Kaplan-Meier curves revealed notably inferior RFS, CSS, and OS of patients who were candidates for adjuvant immunotherapy. Multivariate analysis revealed that pathological T and N grade and lymphovascular invasion (LVI) status were independent risk factors for poor RFS, CSS, and OS. CONCLUSION: In total, 44.8% of patients were candidates for adjuvant immunotherapy. In addition to pathological T and N status, LVI was a significant predictor of survival, and may thus play a pivotal role in the selection of patients eligible for adjuvant immunotherapy.

Prognosis based on postoperative PSA levels and treatment in prostate cancer with lymph node involvement.

BACKGROUND: The therapeutic role of pelvic lymph node dissection (PLND) during radical prostatectomy (RP) for prostate cancer is not established. In clinical practice, PLND is primarily performed in cases of high-risk prostate cancer. The detection of lymph node metastasis plays a crucial role in determining the need for subsequent treatments. This study aims to evaluate the prognosis of prostate cancer patients with lymph node involvement (LNI) by stratifying them based on postoperative prostate-specific antigen (PSA) levels to identify biomarkers that can guide postoperative treatment strategies. METHODS: Analysis was conducted on 383 patients, selected from 572 initially eligible, who underwent RP with LNI across 33 Japanese Urological Oncology Group institutions from 2006 to 2019. Patients were grouped according to postoperative PSA levels and salvage treatments received. Follow-up focused on castration resistance-free survival (CRFS), metastasis-free survival (MFS), and overall survival (OS). RESULTS: In the persistent PSA group (PSA ≥ 0.1 ng/mL), CRFS and MFS were significantly shorter compared to the non-persistent PSA group (PSA < 0.1 ng/mL), and there was a tendency for shorter OS. In the persistent PSA group, patients with postoperative PSA values above the median (PSA ≥ 0.52 ng/mL) showed shorter CRFS and MFS. Furthermore, in the PSA ≥ 0.52 group, androgen deprivation therapy (ADT) plus radiotherapy (RT) combination had prolonged CRFS and MFS compared with ADT alone. CONCLUSIONS: This study provides valuable insights into stratifying patients based on postoperative PSA levels to tailor postoperative treatment strategies, potentially improving the prognosis of prostate cancer patients with LNI.

Prostate cancer and liquid biopsies: Clinical applications and challenges.

Liquid biopsy has emerged as a valuable and minimally invasive tool for real-time detection of clinically actionable abnormalities across various cancer types. Its applicability is particularly compelling in the realm of prostate cancer, where novel therapeutic agents, including those targeting DNA repair systems, are under development. Despite these advancements, challenges persist in effectively screening for prostate cancer, enhancing risk stratification, and determining optimal approaches for treating advanced disease. Consequently, there is a pressing need for improved biomarkers to aid clinicians in decision-making within these contexts. Cell-free DNA and extracellular vesicle analysis have demonstrated promise in diagnosis, prognostication, assessment of treatment responses, and identification of emerging mechanisms of resistance. Nevertheless, obstacles must be addressed before liquid biopsies can be integrated into routine clinical practice. These challenges encompass preanalytical considerations such as sample collection and storage, methods of extracellular vesicle isolation and enrichment, and the need for enhanced interpretation of generated sequencing data. This review provides a comprehensive overview of current clinical opportunities in managing prostate cancer through blood-based liquid biopsy, highlighting the progress made, and acknowledging the challenges that remain. Additionally, we discuss the next steps required for the effective implementation of liquid biopsies in guiding personalized treatment strategies for prostate cancer.

Prognostic significance of subclassifying pathological T3 upper tract urothelial carcinoma: Results from a multicenter cohort study.

OBJECTIVE: The population with pathological T3 (pT3) upper tract urothelial carcinoma (UTUC) is heterogeneous, thereby making prognostication challenging. We assessed the clinical ramifications of subclassifying pT3 UTUC after nephroureterectomy. METHODS: We conducted a retrospective analysis including 308 patients who underwent nephroureterectomy for pT3N0-1M0 UTUC. pT3 was subclassified into pT3a and pT3b based on invasion of the peripelvic and/or periureteral fat. Cox's proportional hazard models were utilized to determine the significant prognosticators of oncological outcomes, encompassing intravesical recurrence-free survival, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival. RESULTS: Multivariate analysis elucidated that pT3b status, pathological N1 status, and lymphovascular invasion status were independent risk factors for an unfavorable RFS and CSS. Although the RFS and CSS of patients with pT3b UTUC were superior to those in patients with pT4 UTUC, no significant disparities were detected between patients with pT3a and pT2. CONCLUSION: Our findings demonstrate that pT3 UTUC with peripelvic/periureteral fat invasion is independently associated with metastasis and cancer-specific death after nephroureterectomy. These findings provide patients and physicians with invaluable insight into the risk for disease progression in pT3 UTUC patients.

Validation study on the 2 mm diameter cutoff in lymph node-positive cases following radical prostatectomy in accordance with the AJCC/UICC TNM 8th edition: Real-world data analysis from a Japanese cohort.

OBJECTIVES: The American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) 8th edition has proposed micrometastasis as a lymph node metastasis (LN+) of diameter ≤2 mm in prostate cancer. However, supporting evidence has not described. We evaluated LN+ patients' survival after radical prostatectomy (RP) based on the LN maximum tumor diameter (MTD). METHODS: Data from 561 LN+ patients after RP and pelvic LN dissection (PLND) treated between 2006 and 2019 at 33 institutions were retrospectively investigated. Patients were stratified by a LN+ MTD cutoff of 2 mm. Outcomes included castration resistance-free survival (CRFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: In total, 282 patients were divided into two groups (LN+ MTD >2 mm [n = 206] and ≤2 mm [n = 76]). Patients of LN+ status >2 mm exhibited significantly decreased CRFS and MFS, and poorer CSS and OS. No patients developed CRPC in the LN+ status ≤2 mm group when the PLND number was ≥14. Multivariate analysis showed the number of LN removed, RP Gleason pattern 5, and MTD in LN+ significantly predicted CRFS. CONCLUSIONS: Patients of LN+ status ≤2 mm showed better prognoses after RP. In all the patients in the ≤2-mm group, the progression to CRPC could be prevented with appropriate interventions, particularly when PLND is performed accurately. Our findings support the utility of the pN substaging proposed by the AJCC/UICC 8th edition; this will facilitate precision medicine for patients with advanced prostate cancer.

Changes in the treatment landscape of metastatic hormone-sensitive prostate cancer following approval of upfront androgen receptor signaling inhibitors: A multicenter study.

BACKGROUND: A multicenter database was utilized to examine the current treatment landscape and clinical outcomes among patients with metastatic hormone-sensitive prostate cancer (mHSPC) following approval of upfront androgen receptor signaling inhibitors (ARSIs). METHODS: We retrospectively analyzed patients with mHSPC who commenced treatment between February 2018 and June 2023. The Kaplan-Meier method was used to assess oncological outcomes, including time to castration-resistant prostate cancer (CRPC), progression-free survival 2 (PFS2, duration from initial treatment to tumor progression during second-line treatment), cancer-specific survival (CSS), and overall survival (OS). Cox regression analyses were performed to determine the impact of treatment choices on oncological outcomes. In addition, the incidence rate of adverse events was assessed. RESULTS: In total, 829 patients were analyzed; 42.5% received ARSIs with androgen deprivation therapy (ADT), 44.0% received combined androgen blockade (CAB), and 13.5% received ADT alone. Kaplan-Meier curves and multivariate Cox regression analyses indicated higher rates of CRPC and shorter PFS2 in patients treated with CAB versus ARSIs with ADT. By contrast, CSS and OS were not significantly different between the ARSI with ADT group and the CAB group. Grades 3-4 adverse events occurred in 1.9% of patients receiving CAB and 6.0% of those receiving ARSIs with ADT. CONCLUSIONS: Initial treatment with ARSIs in combination with ADT resulted in a longer time to CRPC and longer PFS2 compared to CAB. Although CAB and ADT alone were associated with fewer adverse events, ARSIs with ADT should be considered a first-line treatment option given its superior oncological outcomes.

The clinical impact of ureteroscopy for upper tract urothelial carcinoma: A multicenter study.

BACKGROUND: With the development of kidney-sparing surgery and neoadjuvant chemotherapy, ureteroscopic biopsy (URSBx) has become important for the management of upper tract urothelial carcinoma (UTUC). METHODS: We retrospectively analyzed data from 744 patients with UTUC who underwent radical nephroureterectomy (RNU), stratified into no ureteroscopy (URS), URS alone, and URSBx groups. Intravesical recurrence-free survival (IVRFS) was examined using the Kaplan-Meier method. We conducted Cox regression analyses to identify risk factors for IVR. We investigated differences between clinical and pathological staging to assess the ability to predict the pathological tumor stage and grade of RNU specimens. RESULTS: Kaplan-Meier curves and multivariate Cox regression revealed significantly more IVR and inferior IVRFS in patients who underwent URS and URSBx. Superficial, but not invasive, bladder cancer recurrence was more frequent in the URS and URSBx groups than in the no URS group. Clinical and pathological staging agreed for 55 (32.4%) patients. Downstaging occurred for 48 (28.2%) patients and clinical understaging occurred for 67 (39.4%) patients. Upstaging to muscle-invasive disease occurred for 39 (35.8%) of 109 patients with ≤cT1 disease. Clinical and pathological grading were similar for 72 (42.3%) patients. Downgrading occurred for 5 (2.9%) patients, and clinical undergrading occurred for 93 (54.7%) patients. CONCLUSION: URS and URSBx instrumentation will be risk factors for superficial, but not invasive, bladder cancer recurrence. Clinical understaging/undergrading and upstaging to muscle-invasive disease occurred for a large proportion of patients with UTUC who underwent RNU. These data emphasize the challenges involved in accurate UTUC staging and grading.

Long-term outcomes of radical prostatectomy versus low-dose-rate brachytherapy in patients with intermediate-risk prostate cancer: Propensity score matched comparison.

PURPOSE: To compare long-term outcomes of radical prostatectomy (RP) and low-dose-rate brachytherapy (LDR-BT) using propensity score-matched analysis in patients with clinically localized, intermediate-risk prostate cancer (PCa). METHODS: Between October 2003 and March 2014, our institution treated 1241 patients with intermediate-risk PCa (RP: n = 531; LDR-BT: n = 710). Biochemical recurrence (BCR) was defined as prostate-specific antigen (PSA) levels of 0.2 ng/ml or greater for RP, and as PSA nadir plus 2 ng/ml or higher (Phoenix definition) for LDR-BT. We calculated propensity scores by multivariate logistic regression based on covariates that included age, pretreatment PSA, biopsy Gleason grade, the percentage of positive biopsy cores (PPBC), and clinical T stage. RESULTS: Median follow-up was 108 months for RP and 99 months for LDR-BT. After propensity score adjustment, a total of 642 (321 each) patients remained for further analysis. Kaplan-Meier curves showed no statistically significant difference in overall survival (OS) (p = 0.99). LDR-BT was associated with improved BCR-free survival and salvage therapy-free survival  compared to RP (p < 0.001), and RP was associated with improved metastasis-free survival (MFS, p < 0.001). CONCLUSION: BCR cannot be a surrogate for survival comparison, primarily due to differences between treatment modalities in how this term was defined post-therapy. Long-term follow-up showed that RP was associated with lower MFS in intermediate-risk PCa. However, this has not yet translated into superior OS.

Comparison of neoadjuvant and adjuvant chemotherapy for upper tract urothelial carcinoma in real-world practice: a multicenter retrospective study.

BACKGROUND: Multiple studies have demonstrated the effectiveness of neoadjuvant chemotherapy and adjuvant chemotherapy in patients with upper tract urothelial carcinoma compared with surgery alone. However, no clinical trial has established the superiority of neoadjuvant chemotherapy or adjuvant chemotherapy in terms of perioperative outcomes. METHODS: We conducted a retrospective analysis encompassing 164 upper tract urothelial carcinoma patients who underwent radical nephroureterectomy and received perioperative chemotherapy. Of these patients, 65 (39.6%) and 99 (60.4%) received neoadjuvant chemotherapy and adjuvant chemotherapy, respectively. Recurrence-free survival and cancer-specific survival were computed using the Kaplan-Meier method. Additionally, we conducted Cox regression analyses to evaluate the risk factors for recurrence-free survival and cancer-specific survival. RESULTS: Pathological downstaging was seen in 37% of the neoadjuvant chemotherapy group. However, no pathological complete response was observed in this cohort. The Kaplan-Meier curves demonstrated significantly lower recurrence-free survival and cancer-specific survival in patients who received adjuvant chemotherapy. Multivariate Cox regression analysis revealed patients treated with adjuvant chemotherapy exhibited a marked association with inferior recurrence-free survival and cancer-specific survival. CONCLUSION: Our study has suggested that neoadjuvant chemotherapy would be more effective in high-risk upper tract urothelial carcinoma patients compared with adjuvant chemotherapy.

Comparison of outcomes in high-risk prostate cancer patients treated with low-/high-dose-rate brachytherapy plus external beam radiotherapy.

BACKGROUND: Although brachytherapy is a standard treatment option for patients with high-risk prostate cancer, only a few studies have compared low-dose-rate brachytherapy (LDR-BT) and high-dose-rate brachytherapy (HDR-BT). We applied propensity score-based inverse probability treatment weighting (IPTW) to compare oncological outcomes for LDR-BT and HDR-BT. METHODS: We retrospectively assessed prognosis in 392 patients with high-risk localized prostate cancer who had undergone brachytherapy plus external beam radiation. IPTW was applied to adjust the Kaplan-Meier survival analyses and Cox proportional hazards regression analyses, with the goal of minimizing bias from patient background. RESULTS: The IPTW-adjusted Kaplan-Meier survival analyses showed no statistically significant differences for time to biochemical recurrence, clinical progression, castration-resistant prostate cancer, or death from any cause. The IPTW-adjusted Cox regression analyses also showed that the modality of brachytherapy was not an independent factor in these oncological outcomes. Notably, the two groups differed regarding complications; LDR-BT was associated with a higher rate of acute grade ≥ 2 GU toxicity, and late grade 3 toxicity was noted only in HDR-BT. CONCLUSION: Our analysis of long-term outcomes in patients with high-risk localized prostate cancer shows no significant differences in oncological outcomes between LDR-BT and HDR-BT, but some differences in toxicity, and offers patients and clinicians useful information in deciding management strategies for high-risk localized prostate cancer.

The prognostic significance of the clinical T stage and Grade Group in patients with locally advanced prostate cancer treated via high-dose-rate brachytherapy and external beam radiation.

BACKGROUND: Although the optimal management of locally advanced prostate cancer (PCa) remains unclear, local definitive therapy, thus combined radiotherapy and androgen deprivation, is one option. We evaluated the long-term outcomes of patients with locally advanced PCa who underwent high-dose-rate brachytherapy (HDR-BT) and external beam radiation therapy (EBRT). METHODS: We retrospectively analyzed 173 patients with locally advanced PCa (cT3a-4N0-1M0) who underwent HDR-BT and EBRT. We employed Cox's proportional hazards models to identify pre-treatment predictors of oncological outcomes. Treatment outcomes (biochemical recurrence-free survival [BCRFS], clinical progression-free survival [CPFS], and castration-resistant prostate cancer-free survival [CRPCFS] were compared according to the combination of the pre-treatment predictors. RESULTS: The 5-year BCRFS, CPFS, and CRPCFS rates were 78.5, 91.7, and 94.4% respectively; there were two PCa deaths. Multivariate analysis revealed that the clinical T stage (cT3b and cT4) and Grade Group (GG) 5 status were independent risk factors for poor BCRFS, CPFS, and CRPCFS. In the GG ≤ 4 group, the Kaplan-Meier curves for BCRFS, CPFS, and CRPCFS revealed excellent outcomes. However, in the GG5 group, patients with cT3b and cT4 PCa evidenced significantly poorer oncological outcomes than those with cT3a PCa. CONCLUSION: The clinical T stage and GG status were significantly prognostic of oncological outcomes in patients with locally advanced PCa. In patients of GG ≤ 4 PCa, HDR-BT was effective even in patients with cT3b or cT4 PCa. However, in patients with GG5 PCa, careful monitoring is essential, particularly of patients with cT3b or cT4 PCa.

Clinical characteristics of secondary bladder cancer developing after low-/high-dose-rate brachytherapy to treat localized prostate cancer.

BACKGROUND: To explore correlations between the clinical attributes of secondary bladder cancer and brachytherapy, we retrospectively reviewed our institutional database on patients with localized prostate cancer who underwent low-dose-rate brachytherapy (LDR-BT) or high-dose-rate brachytherapy (HDR-BT) with or without external beam radiation therapy (EBRT) or radical prostatectomy (RP). METHODS: From October 2003 to December 2014, 2551 patients with localized prostate cancer were treated at our institution. Of these, data on 2163 were available (LDR-BT alone: n = 953; LDR-TB with EBRT: n = 181; HDR-BT with EBRT: n = 283; RP without EBRT: n = 746). The times of secondary bladder cancer development subsequent to radical treatment, and their clinical characteristics, were studied. RESULTS: Age-adjusted Cox's regression analyses indicated that brachytherapy did not significantly impact the incidence of secondary bladder cancer. However, the pathological characteristics of such cancer differed between patients treated via brachytherapy and RP without EBRT; invasive bladder cancer was more common in such patients. CONCLUSION: The risk for secondary bladder cancer was not significantly increased after brachytherapy compared to non-irradiation therapy. However, brachytherapy patients exhibited a higher incidence of invasive bladder cancer. Therefore, meticulous follow-up is crucial for early detection and treatment of bladder cancer in such patients.

Patients with PSA below 0.2 ng/mL at 8 years post high-dose-rate brachytherapy have an extremely low risk of subsequent recurrence.

OBJECTIVES: We have analyzed the long-term follow-up data of patients with prostate cancer (PCa) who underwent high-dose-rate brachytherapy (HDR-BT) and external beam radiotherapy (EBRT) combined with long-term androgen deprivation therapy (ADT). The objective was to determine the optimal time for cessation of PSA monitoring after HDR-BT. METHODS: We included 309 patients with clinical stage T1c-T4 N0-1 M0 PCa who received HDR-BT and EBRT combined with long-term ADT between 2005 and 2018. We stratified the patients based on their prostate-specific antigen (PSA) levels and identified the factors associated with biochemical recurrence (BCR) and clinical progression (CP). RESULTS: The median follow-up duration was 98 months (range: 31-207 months). Among the 306 patients, 76 developed BCR and 47 developed CP subsequently. We found that the PSA levels at 3, 5, and 8 years significantly correlated with the oncological outcomes of brachytherapy. No patient with a PSA level ≤ 0.2 ng/mL at 8 years later developed BCR or CP. CONCLUSION: Our long-term data suggest that in the presence of a PSA level ≤ 0.2 ng/mL at 8 years later, PSA monitoring may be safely discontinued due to the extremely low risk of subsequent oncological events. The data presented in this study will assist clinicians in determining the optimal management strategy for patients with PCa following HDR-BT and EBRT combined with long-term ADT.

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.

Clinical significance of unfavorable findings in intermediate-risk prostate cancer patients for predicting treatment outcomes after contemporary, dose-escalated multimodal radiotherapy.

PURPOSE: Few studies have documented the long-term oncological outcomes of favorable and unfavorable intermediate-risk (IR) prostate cancer patients treated via contemporary high-dose irradiation. We analyzed the ultimate clinical outcomes of such patients using the current risk sub-stratification schema. PATIENTS AND METHODS: We included 693 patients with localized IR prostate cancer treated via low-dose-rate brachytherapy (LDR-BT) with or without external beam radiation (EBRT) and with or without androgen-deprivation therapy (ADT) in a single institution. Treatment outcomes (biochemical recurrence-free survival [BCRFS] and clinical progression-free survival [CPFS]) were compared according to the numbers of unfavorable findings. RESULTS: Out of the 693 IR patients, 292 (42.1%) exhibited favorable disease; the remaining 401 (57.9%) exhibited unfavorable disease. Compared with favorable IR status, unfavorable IR status was associated with shorter BCRFS and CPFS (p < 0.001 and p < 0.001, respectively). Patients with two to three unfavorable factors experienced the worst oncological outcomes (p < 0.001 and p < 0.001). Although patients with one or no unfavorable factors responded similarly to LDR-BT monotherapy, this treatment modality was insufficient for preventing biochemical and clinical progression in patients with multiple unfavorable findings. CONCLUSION: Long-term treatment outcomes indicate that patients with IR disease scheduled for LDR-BT should undergo multimodal irradiation if they exhibit two or more unfavorable factors at diagnosis.

Pre-pembrolizumab neutrophil-to-lymphocyte ratio (NLR) predicts the efficacy of second-line pembrolizumab treatment in urothelial cancer regardless of the pre-chemo NLR.

Neutrophil-to-lymphocyte ratio (NLR) was reported to be associated with prognosis of urothelial cancer (UC) patients receiving systemic chemotherapy or immunotherapy. However, it has not been elucidated how preceding first-line chemotherapy affects NLR and subsequent second-line pembrolizumab treatment. This multicenter study analyzed 458 patients with metastatic UC who received first-line chemotherapy and second-line pembrolizumab with regard to pre-chemotherapy and pre-pembrolizumab NLR in association with the efficacy of chemotherapy and pembrolizumab treatment. NLR was increased in 47% while decreased in 53% of patients before and after first-line chemotherapy. High pre-chemotherapy NLR (≥ 3) was significantly associated with unfavorable overall (OS, P = 0.0001) and progression-free (P < 0.0001) survivals after first-line chemotherapy. However, pre-chemotherapy NLR showed only modest influence on radiological response and survival after second-line pembrolizumab treatment, whereas pre-pembrolizumab NLR showed higher association. NLR decrease was associated with partial response or greater objective response by first-line chemotherapy, while NLR increase was associated with higher patient age. In conclusion, immediate pre-chemotherapy and pre-pembrolizumab NLR was significantly associated with efficacy of the following treatment, respectively. However, even patients with high pre-chemotherapy NLR achieved favorable OS if they had their NLR reduced by chemotherapy, whereas those with high pre-chemotherapy NLR yielded unfavorable OS if they had their NLR remained high after chemotherapy, suggesting that chemotherapy may have differential effect on the efficacy of subsequent pembrolizumab treatment in UC patients.

Prognostic value of PSA bounce after definitive radiotherapy revisited.

BACKGROUND: Prostate-specific antigen (PSA) bounce after definitive radiotherapy has been reported as a predictor of improved biochemical recurrence-free survival (BCRFS). We revisited this phenomenon to confirm its clinical impact on oncological outcomes in patients with long-term follow-up who were free of biochemical recurrence (BCR) at least 3 years after treatment. MATERIALS AND METHODS: A total of 541 patients with localized, intermediate-risk prostate cancer underwent low-dose rate brachytherapy with iodine-125 seeds with or without supplemental external beam radiotherapy in combination. Neoadjuvant hormonal therapy was administered to 273 patients (50.5%) with a median duration of 3 months (range 1-108 months). PSA bounce was defined as ≥ 0.2 ng/ml increase above the interval PSA nadir, followed by a decrease below that value. RESULTS: The median age was 69 years (range 49-90 years). The median follow-up duration was 102 months (range 36-205 months). One-hundred and fifty patients (27.7%) had PSA bounce with a median magnitude of 0.47 ng/ml (range 0.2-3.19 ng/ml). Age was significantly associated with the occurrence of PSA bounce [age: hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.93-0.98]. It was found to be independently associated with a decreased risk for BCR (HR 0.29; 95% CI 0.12-0.69) and clinical progression (HR 0.44; 95% CI 0.95-0.98). CONCLUSION: PSA bounce indicated a favorable BCRFS and clinical progression-free survival in patients who had been free of BCR for at least 3 years after definitive radiotherapy.