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.

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.

Does age impact clinical outcomes of radical nephroureterectomy in the elderly?-results from a multicenter retrospective study.

Background: Few studies have addressed the efficacy of nephroureterectomy for managing upper tract urothelial carcinoma (UTUC) in very elderly patients (those aged 85 years and older). We aimed to elucidate the association between age and clinical outcomes in patients with UTUC who underwent radical nephroureterectomy. Methods: We retrospectively analyzed data from 847 patients who underwent nephroureterectomy for UTUC. These patients were classified into four age brackets: young (≤64 years, n=177), intermediate (65-74 years, n=300), elderly (75-84 years, n=312), and very elderly (≥85 years, n=58). We applied logistic regression models to ascertain predictors of postoperative complications. Cox's proportional hazards models were used to evaluate key prognostic factors affecting non-urothelial tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS). Results: In all, 56 patients reported postoperative complications. An Eastern Cooperative Oncology Group performance status ≥2 was identified as a significant predictor for postoperative complications whereas age did not show a noteworthy correlation. Kaplan-Meier survival analyses indicated that very elderly patients had notably poorer OS than younger groups. Nevertheless, the differences in NUTRFS and CSS across the age brackets were not statistically significant. In multivariable analyses, very elderly age was a substantial independent determinant of OS but not NUTRFS or CSS. Conclusions: The therapeutic benefits of surgical procedures are relatively consistent across age groups. This underscores the potential of considering surgical treatment for UTUC in patients aged 85 and above, provided they are deemed fit to withstand the surgical rigors and associated invasiveness.

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.

Perioperative renal function change and oncological outcomes of radical nephroureterectomy in patients with upper tract urothelial carcinoma: A multicenter retrospective study.

BACKGROUND: The effect of radical nephroureterectomy (RNUx) on postoperative renal function in patients diagnosed with upper tract urothelial carcinoma (UTUC) has not been thoroughly explored. METHODS: We conducted a retrospective analysis including 785 patients who underwent RNUx for UTUC. We assessed the preoperative and postoperative estimated glomerular filtration rates (eGFRs) and factors related to the decline in eGFR. Additionally, we examined the effect of comorbidities (diabetes or hypertension) on the postoperative eGFR at 1 year. Cox proportional hazard models were employed to investigate the clinical effect of RNUx on oncological outcomes, including non-urothelial tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: The median preoperative and postoperative eGFR levels were 54.7 and 40.6 ml/min/1.73 m2 respectively. The proportions of patients with preoperative and postoperative eGFR ≥60 mL/min/1.73 m2 were 35.9% and 5.1%, respectively. The median decline in the eGFR after surgery was 26.8%. Patients with preoperative eGFR <60 ml/min/1.73 m2 demonstrated significantly lower odds of a postoperative decline in eGFR of 25% or more. The effect of comorbidities on postoperative eGFR at 1 year was significant (P = 0.048). The 3-year NUTRFS, CSS, and OS rates were 72.9%, 85.2%, and 81.5%, respectively. Preoperative chronic kidney disease was an independent factor associated with inferior NUTRFS, CSS, and OS. CONCLUSION: Different degrees of impairment of renal function occur among UTUC patients. Only 5.1% of patients retain a postoperative eGFR ≥60 ml/min/1.73 m2. Preoperative renal impairment was linked to reduced odds of postoperative eGFR decrease and associated with survival. In addition, the presence of comorbidities had a significant effect on the decline in eGFR. These findings emphasize the importance of developing evidence-based perioperative treatment strategies for UTUC patients with impaired renal function.

Site-Specific Differences of Eligibility for Adjuvant Immunotherapy Among Urothelial Carcinoma Patients Treated With Radical Surgery: Results From a Multicenter Cohort Study.

BACKGROUND: The CheckMate274 trial has reported enhanced disease-free survival rates in patients with stage pT3-4/ypT2-4 or pN+ urothelial carcinoma (UC) undergoing adjuvant nivolumab therapy. This study compares prognostic differences between urothelial carcinoma of the bladder (UCB) and upper tract urothelial carcinoma (UTUC). METHODS: We retrospectively analyzed data from 719 patients with UC who underwent radical surgery, stratifying to patients at stage pT3-4 and/or pN+ without neoadjuvant chemotherapy (NAC) or at ypT2-4 and/or ypN+ with NAC (potential candidates for adjuvant immunotherapy), and to those who were not candidates for adjuvant immunotherapy. We used Kaplan-Meier curves to assess oncological outcomes, particularly nonurothelial tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS). Risk factors were identified by Cox regression analysis. RESULTS: Kaplan-Meier curves showed significantly lower NUTRFS, CSS, and OS for potential adjuvant immunotherapy candidates than for noncandidates in each UCB and UTUC group. NUTRFS, CSS, and OS did not differ significantly between adjuvant immunotherapy candidates with UBC or UTUC. Trends were similar among patients ineligible for adjuvant immunotherapy. Pathological T stage (pT3-4 or ypT2-4), pathological N stage, and lymphovascular invasion (LVI) were independent predictors of oncological outcomes on multivariate analysis. CONCLUSION: The criteria for adjuvant immunotherapy candidates from the CheckMate 274 trial can also effectively stratify UC patients after radical surgery. Substantial clinical significance is attached to LVI status as well as to pathological T and N status, suggesting that LVI status should be considered when selecting suitable candidates for adjuvant immunotherapy.

Effect of a variant histology on the oncological outcomes of Japanese patients with upper tract urothelial carcinomas after radical nephroureterectomy: a multicenter retrospective study.

Background: An earlier systematic review and meta-analysis found that patients with a certain histological variant of upper tract urothelial carcinoma (UTUC) exhibited more advanced disease and poorer survival than those with pure UTUC. A difference in the clinicopathological UTUC characteristics of Caucasian and Japanese patients has been reported, but few studies have investigated the clinical impact of the variant histology in Japanese UTUC patients. Methods: We retrospectively enrolled 824 Japanese patients with pTa-4N0-1M0 UTUCs who underwent radical nephroureterectomy without neoadjuvant chemotherapy. Subsequently, we explored the effects of the variant histology on disease aggressiveness and the oncological outcomes. We used Cox's proportional hazards models to identify significant predictors of oncological outcomes, specifically intravesical recurrence-free survival (IVRFS), recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Results: Of the 824 UTUC patients, 32 (3.9%) exhibited a variant histology that correlated significantly with a higher pathological T stage and lymphovascular invasion (LVI). Univariate analysis revealed that the variant histology was an independent risk factor for suboptimal RFS, CSS, and OS. However, significance was lost on multivariate analyses. Conclusions: The variant histology does not add to the prognostic information imparted by the pathological findings after radical nephroureterectomy, particularly in Japanese UTUC patients.

Impact of timing of urinary drainage on clinical outcomes in patients with obstructive pyelonephritis associated with upper urinary tract stones: a propensity score-matched analysis.

OBJECTIVE: We aimed to assess the impact of the timing of urinary drainage on clinical outcomes in patients with obstructive pyelonephritis (OPN) associated with upper urinary tract (UUT) stones. METHODS: We retrospectively evaluated the multicenter dataset of 240 patients with OPN associated with UUT stones who underwent urinary drainage. We divided the patients into two groups depending on the timing of urinary drainage; emergency drainage, defined as within 12 h from admission, and delayed drainage, defined as between 12 and 48 h from admission. The outcomes were the length of hospital stay, time to leukocyte normalization, and time to body temperature normalization. One-to-two propensity score matching (PSM) was applied to minimize the effect of confounders between the two groups. Subsequently, predictive patient factors for emergency drainage were analyzed using the logistic regression model. RESULTS: Only the time from admission to normal body temperature was significantly shorter in the emergency drainage group when compared with the delayed drainage group (median: 2 vs. 3 days; p = 0.02), while there was no difference in time from drainage to body temperature normalization between the two groups. On multivariable analysis, high pretreatment C-reactive protein (CRP) was associated with implementing emergency drainage within 12 h. CONCLUSIONS: The timing of urinary drainage was only associated with the duration of high fever, but it did not affect the postdrainage course. Emergency urinary drainage is more likely to be performed in severe patients, such as high pretreatment CRP.

Association between comorbidities and survival in patients with metastatic urothelial carcinoma treated with pembrolizumab.

BACKGROUND: This study aims to investigate the relationship between comorbidities and survival in patients with mUC treated with pembrolizumab as a second-line treatment. METHODS: From February 2018 to October 2021, we analyzed the data of 185 consecutive patients with metastatic UC who received pembrolizumab as second-line therapy at The Jikei University Hospital and five affiliated hospitals. We used the Charlson Comorbidity Index (CCI) to assess the comorbidities. The outcomes of interest were progression-free survival (PFS) and overall survival (OS). To compare the survival differences, inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and the IPTW-adjusted Cox regression hazards model were used. RESULTS: After IPTW adjustment, patient characteristics were well-balanced between patients with high CCI and those with low CCI. The IPTW-adjusted Kaplan-Meier curves of PFS and OS based on CCI revealed that the patients with high CCI (2 or more) had a shorter PFS (median, 1.6 vs. 2.8 months) and a shorter OS (median, 12.4 vs. 18.8 months) (0-1). Similarly, in the IPTW-adjusted Cox regression hazards model, patients with high CCI had significantly shorter PFS [HR, 1.84 (95% CI 1.26-2.68; p = 0.002)] and OS [HR, 1.98 (95% CI 1.20-3.27; p = 0.008)] than those with lower CCI. CONCLUSIONS: High CCI was associated with a higher risk of disease progression as well as overall mortality in mUC patients treated with second-line pembrolizumab.

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.

Clinical Significance of Intraductal Carcinoma of the Prostate After High-Dose Brachytherapy With External Beam Radiation Therapy: A Single Institution Series and an Updated Meta-Analysis.

BACKGROUND: We compared oncological outcomes between prostate cancer (PCa) patients with and without intraductal carcinoma of the prostate (IDC-P) after high-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT). METHODS: We performed a retrospective analysis of 138 patients with clinically high-risk, very high-risk, or locally advanced PCa who received HDR-BT with EBRT. Of these, 70 (50.7 %) patients were diagnosed with IDC-P; 68 (49.3 %) patients with acinar adenocarcinoma of prostate. The oncological outcomes, including biochemical recurrence-free survival (BCRFS) and clinical progression-free survival (CPFS), were assessed using Kaplan-Meier curves. Additionally, Cox proportional hazards models were used to identify significant prognostic indicators or biochemical recurrence (BCR). Meta-analysis of existing literatures was performed to evaluate the risk of BCR in patients with IDC-P after radiation therapy, compared to those without IDC-P. RESULTS: Kaplan-Meier curves demonstrated significantly inferior BCRFS and CPFS in patients with IDC-P. Multivariate analysis revealed that IDC-P and Grade Group 5 status were associated with increased BCR risk. in our meta-analysis, IDC-P was associated with BCR (HR = 2.13, P = .003). CONCLUSION: Amongst the patients who received HDR-BT, patients with IDC-P displayed significantly more rapid disease progression, compared with patients who did not have IDC-P.

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.

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.

Phenomenological interpretations of the mechanism for the concentration-dependent positive effect of antibiotic lincomycin on Streptomyces coelicolor A3(2).

The antibiotic lincomycin binds to the 23S ribosomal RNA peptidyl transferase loop region to inhibit protein synthesis. However, lincomycin can also stimulate the growth and secondary metabolism of actinomycetes in a concentration-dependent manner. In Streptomyces coelicolor A3(2), lincomycin stimulates the production of the blue-pigmented antibiotic actinorhodin at concentrations below the minimum inhibitory concentration. To better understand the molecular mechanism underlying these concentration-dependent positive effects, this study investigated how the target molecule, the ribosome, undergoes dynamic changes in the presence of lincomycin and explored the ribosome-related factors involved. Lincomycin, at a concentration that stimulates actinorhodin production of S. coelicolor A3(2), could restore temporarily arrested ribosome function by utilizing ribosome-related proteins and translation factors, presumably under the control of the transcription factor WblC protein that confers intrinsic resistance to multiple translation-inhibiting antibiotics, to eventually produce stable and active ribosomes even during the late growth phase. This qualitatively and quantitatively positive ribosome alteration can be advantageous for producing actinorhodin biosynthetic enzymes. A series of gene expression and biochemical analyses revealed that lincomycin at the concentration that induces ribosomal stabilization in S. coelicolor A3(2) could influence the localization of the 20S proteasome-related proteins, resulting in reduced proteasome activity. These findings suggest that the functional analysis of 20S proteasome represents a potential pivotal challenge for understanding the molecular mechanism of ribosome stabilization induced by lincomycin. Therefore, as lincomycin can dynamically alter its target molecule, the ribosome, we discuss the future issues and prospects for an increased understanding of the concentration-dependent properties of antibiotics. IMPORTANCE Antibiotics were originally defined as chemical compounds produced by a microbe that inhibits the growth of other microbes. However, an unexplained effect of this is that a low concentration of antibiotics, such as those below the minimum inhibitory concentration, can positively affect microbial growth and metabolism. The secondary metabolic activation of streptomycetes in the presence of the translation-inhibiting antibiotic lincomycin illustrates the concentration-dependent positive effect of the antibiotic. The significance of this study is that the phenomenological interpretation of the molecular mechanism of the concentration-dependent positive effect of lincomycin in Streptomyces coelicolor A3(2) has provided novel insight into the possible role of antibiotics in making their target molecules stable and active with the assistance of various related factors that benefit their function. Further exploration of this idea would lead to an essential understanding of antibiotics, including why actinomycetes make them and their role in nature.

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.

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.

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.

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.

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.