ctDNA predicts clinical T1a to pathological T3a upstaging after partial nephrectomy.

Most patients diagnosed with clear cell renal cell carcinoma (ccRCC) are also detected with small and organ-confined tumors, and the majority of these are classified as clinical tumor stage 1a (cT1a). A considerable proportion of patients with cT1 RCC shows tumor upstaging to pathological stage 3a (pT3a), and these patients have worse oncological outcomes. The role of circulating tumor DNA (ctDNA) in RCC has been limited to monitoring treatment response and resistance. Therefore, the present study aimed to evaluate the potential of ctDNA in predicting pT3a upstaging in cT1a ccRCC. We sequenced plasma samples preoperatively collected from 48 patients who had undergone partial nephrectomy for cT1a ccRCC using data from a prospective cohort RCC. The ctDNA were profiled and compared with clinicopathological ccRCC features to predict pT3a upstaging. Associations between ctDNA, tumor complexity, and pT3a upstaging were evaluated. Tumor complexity was assessed using the anatomical classification system. Univariate analysis used chi-squared and Student's t-tests; multivariate analysis considered significant factors from univariate analyses. Of the 48 patients with cT1a ccRCC, 12 (25%) were upstaged to pT3a, with ctDNA detected in 10 (20.8%), predominantly in patients with renal sinus fat invasion (SFI; n = 8). Among the pT3a group, ctDNA was detected in 75%, contrasting with only 2.8% in patients with pT1a (1/36). Detection of ctDNA was the only significant preoperative predictor of pT3a upstaging, especially in SFI. This study is the first to suggest ctDNA as a preoperative predictor of pT3a RCC upstaging from cT1a based on preoperative radiological images.

Role of Maximal Transurethral Resection Preceding Partial Cystectomy for Muscle-Invasive Bladder Cancer.

PURPOSE: We aimed to evaluate whether maximal transurethral resection (TUR) affects the oncological outcome of partial cystectomy (PC) performed in patients with muscle-invasive bladder cancer (MIBC), although radical cystectomy (RC) and trimodal therapy (TMT) are regarded as standard treatments for MIBC. METHODS: In this retrospective study, we evaluated the data of 98 patients who underwent PC due to MIBC between January 2006 and December 2018. Of the 98 patients, 71 underwent maximal TUR. We evaluated the recurrence-free survival (PFS), pelvic recurrence-free survival (pPFS), cancer-specific survival (CSS), and overall survival (OS) using the Kaplan-Meier method according to the maximal TUR status. Variables associated with survival were analyzed using Cox regression analyses. RESULTS: The 5-year PFS (42.5% vs. 20.3%, p = 0.008), pPFS (50.7% vs. 24.1%, p = 0.003), and CSS (74.0% vs. 51.0%, p = 0.016) were also higher in patients who underwent maximal TUR. The multivariable Cox regression analysis showed that maximal TUR was associated with PFS (hazard ratio [HR] = 0.500, p = 0.029), pPFS (HR = 0.353, p = 0.004), and CSS (HR = 0.416, p = 0.027). However, maximal TUR did not affect the OS (HR = 0.618, p = 0.132). CONCLUSION: PC resulted in acceptable oncological outcomes in patients with MIBC, while maximal TUR played an important role in improving the oncological outcomes. PC after maximal TUR can be suggested as a treatment option for MIBC patients who are unable to undergo RC and TMT.

PD-1 inhibitor plus oncolytic vaccinia virus is a safe and effective treatment option for metastatic renal cell carcinoma.

BACKGROUND: Although a combination of immune checkpoint inhibitors (ICIs) is recommended as the first line treatment option for metastatic renal cell carcinoma (mRCC), several immune-related adverse events (irAEs) occur, especially hepatitis. We explored the therapeutic benefits and safety profile of combining oncolytic vaccinia virus, JX-594, with a programmed cell death protein-1 (PD-1) inhibitor. METHODS: We used early-stage and advanced-stage orthotopic murine mRCC models developed by our group. PD-1 inhibitor monotherapy or a PD-1 inhibitor combined with either JX-594 or a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor were systemically injected through the peritoneum. An immunofluorescence analysis was performed to analyze the tumor immune microenvironment (TIME). irAEs were assessed in terms of hepatitis. RESULTS: In the early-stage mRCC model mice, the combination of JX-594 and a PD-1 inhibitor significantly decreased the primary tumor size and number of lung nodules, compared with the ICI combination, but the JX-594 and PD-1 inhibitor combination and ICI combination did not differ significantly in the advanced-stage mRCC model mice. The JX-594 and PD-1 inhibitor combination induced tumor-suppressing TIME changes in both the early- and advanced-stage mRCC models. Furthermore, mice treated with the ICI combination had significantly greater hepatic injuries than those treated with the JX-594 and PD-1 inhibitor combination which was evaluated in early-stage mRCC model. CONCLUSIONS: The JX-594 and PD-1 inhibitor combination effectively reduced primary tumors and the metastatic burden, similar to ICI combination therapy, through dynamic remodeling of the TIME. Furthermore, hepatitis was significantly decreased in the JX-594 and PD-1 inhibitor combination group, suggesting the potential benefit of that combination for reducing ICI-induced toxicity.

Characteristics of BRCA2 Mutated Prostate Cancer at Presentation.

Genetic alterations of DNA repair genes, particularly BRCA2 in patients with prostate cancer, are associated with aggressive behavior of the disease. It has reached consensus that somatic and germline tests are necessary when treating advanced prostate cancer patients. Yet, it is unclear whether the mutations are associated with any presenting clinical features. We assessed the incidences and characteristics of BRCA2 mutated cancers by targeted sequencing in 126 sets of advanced prostate cancer tissue sequencing data. At the time of diagnosis, cT3/4, N1 and M1 stages were 107 (85%), 54 (43%) and 35 (28%) samples, respectively. BRCA2 alterations of clinical significance by AMP/ASCO/CAP criteria were found in 19 of 126 samples (15.1%). The BRCA2 mutated cancer did not differ in the distributions of TNM stage, Gleason grade group or histological subtype compared to BRCA2 wild-type cancers. Yet, they had higher tumor mutation burden, and higher frequency of ATM and BRCA1 mutations (44% vs. 10%, p = 0.002 and 21% vs. 4%, p = 0.018, respectively). Of the metastatic subgroup (M1, n = 34), mean PSA was significantly lower in BRCA2 mutated cancers than wild-type (p = 0.018). In the non-metastatic subgroup (M0, n = 64), PSA was not significantly different (p = 0.425). A similar trend was noted in multiple metastatic prostate cancer public datasets. We conclude that BRCA2 mutated metastatic prostate cancers may present in an advanced stage with relatively low PSA.

Clinical Outcomes After Urinary Diversion for Malignant Ureteral Obstruction Secondary to Non-urologic Cancer: An Analysis of 778 Cases.

BACKGROUND: This study investigated patient outcomes after urinary diversion in order to manage malignant ureteral obstruction caused by non-urologic cancers and to evaluate predictive factors for overall survival. METHODS: The study retrospectively reviewed patients with non-urologic malignancies who underwent ureteral stenting or percutaneous nephrostomy for ureteral obstruction between 2006 and 2014. The variables for predicting overall survival were identified by Cox regression analysis. RESULTS: The study enrolled 778 patients, including 522 patients who underwent ureteral stenting and 256 patients who underwent percutaneous nephrostomy. Renal function was assessed immediately and then 2 weeks after urinary diversion. The median survival period was 5 months (interquartile range [IQR] 2-12 months). A total of 708 patients died. The patients who received chemotherapy after urinary diversion had a survival gain of 7 months compared with the patients who did not receive subsequent chemotherapy (p < 0.001). The survival rate did not differ between the various types of urinary diversion (p = 0.451). In the multivariate analysis, lower survival rates were significantly associated with male sex; previous chemotherapy without radiotherapy; an increasing number of events related to malignant dissemination; low preoperative hemoglobin (< 10 mg/dL), albumin (< 3 g/dL), and estimated glomerular filtration (< 60 mL/min/1.73 m2) rates; and no subsequent chemotherapy or radiotherapy. CONCLUSIONS: In cases of ureteral obstruction caused by non-urologic malignancies, the overall survival was poor. However, the patients who received chemotherapy after urinary diversion had a survival gain of 7 months. Therefore, urinary diversion could be considered to preserve renal function for subsequent chemotherapy, whereas patients with the poor prognostic factors should be presented with the option of no intervention.

Comparison of Biochemical Recurrence After Robot-assisted Laparoscopic Radical Prostatectomy with Volatile and Total Intravenous Anesthesia.

Aims: Recurrence after cancer surgery is a major concern in patients with cancer. Growing evidence from preclinical studies has revealed that various anesthetics can influence the immune system in different ways. The current study compared the long-term biochemical recurrence of prostate cancer after robot-assisted laparoscopic radical prostatectomy (RALP) in terms of selection of anesthetic agent between total intravenous anesthesia (TIVA) with propofol/remifentanil and volatile anesthetics (VA) with sevoflurane or desflurane/remifentanil. Methods: We followed up oncologic outcomes of patients who underwent RALP from two previous prospective randomized controlled trials, and the outcomes of those who received TIVA (n = 64) were compared with those who received VA (n = 64). The follow-up period lasted from November 2010 to March 2019. Results: Both TIVA and VA groups showed identical biochemical recurrence-free survivals at all-time points after RALP. The following predictive factors of prostate cancer recurrence were determined by Cox regression: colloid input [hazard ratio (HR)=1.002, 95% confidence interval (CI): 1.000-1.003; P = 0.011], initial prostate-specific antigen level (HR=1.025, 95% CI: 1.007-1.044; P = 0.006), and pathological tumor stage 3b (HR=4.217, 95% CI:1.207-14.735; P = 0.024), but not the anesthetic agent. Conclusions: Our findings demonstrate that both TIVA with propofol/remifentanil and VA with sevoflurane or desflurane/remifentanil have comparable effects on oncologic outcomes in patients undergoing RALP.

External validation of the post-varicocele repair semen analysis nomogram to predict total motile sperm count: A multicenter study.

Total motile sperm count is an important parameter for predicting the probability of natural pregnancy. We have externally validated the Samplaski's post-varicocele repair semen analysis nomogram to confirm the predictive accuracy of total motile sperm count. A total of 300 patients who had undergone varicocelectomy between July 2016 and July 2019 from 4 treatment centres were included in this validation cohort study. The predictive performance of the externally validated nomogram was revealed by applying the Pearson correlation coefficient (R = 0.328; 95% confidence interval (CI) 0.220-0.435; p < .001). Compared to Samplaski's nomogram result (R = 0.581; 95% CI 0.186-0.729), our study also revealed a statistically significant rate. However, it had a relatively lower correlation coefficient rate. Notably, the predicted total motile sperm count was lower than the observed post-varicocelectomy total motile sperm count. The calibration plot revealed that the discrepancy between the predicted and observed total motile sperm count was plausible. However, it had low explanatory power in this nomogram model. This validation study demonstrates that the post-varicocele repair Samplaski's nomogram predicts a relatively lower total motile sperm count than the observed count.

The prognostic impact of downgrading and upgrading from biopsy to radical prostatectomy among men with Gleason score 7 prostate cancer.

BACKGROUND: Recently, a new prostate cancer (PC) grading system was introduced, where Gleason score (GS) 7 was divided into 3 + 4 = 7 and 4 + 3 = 7 due to the different prognoses associated with each tumor type. However, whether downgrading or upgrading from needle biopsy (NB) to radical prostatectomy (RP) affects oncologic outcomes is currently unknown. Herein, we investigated the prognostic impact of downgrading and upgrading from NB to RP among men with GS 7 PC. METHODS: We retrospectively reviewed the medical records of 3003 patients with localized PC who underwent RP between 2005 and 2014. We included 692 patients with GS 7 PC on both NB and RP specimens. We analyzed the data using Kaplan-Meier methods and Cox proportional hazard models. RESULTS: Of the 692 patients enrolled in this study, 389 (56.2%) and 303 (43.8%) patients had RP GS 3 + 4 = 7 and RP GS 4 + 3 = 7 PC, respectively. On the basis of NB and RP GS, 264 (38.1%), 125 (18.1%), 142 (20.5%), and 161 (23.3%) patients were classified as 3 + 4/3 + 4, 4 + 3/3 + 4, 3 + 4/4 + 3, and 4 + 3/4 + 3, respectively. Kaplan-Meier curves showed significant differences in biochemical recurrence (BCR)-free survival across the groups (P < .001). In the multivariate analyses, these groups were significantly associated with BCR (4 + 3/3 + 4: hazard ratio [HR], 1.675; 3 + 4/4 + 3: HR, 1.908; and 4 + 3/4 + 3: HR, 2.699). CONCLUSIONS: Downgrading and upgrading from NB to RP was an independent predictor of BCR in men with GS 7 PC, which could be due to the amount of Gleason pattern 4.

Effect of prostate gland weight on the surgical and oncological outcomes of extraperitoneal robot-assisted radical prostatectomy.

BACKGROUND: Robot-assisted radical prostatectomy (RARP) is performed by urologists as one of the surgical procedures for treating prostate cancer. Numerous studies have been published with regard to the impact of prostate weight on performing RARP but were limited by the insufficient number of patients and use of the transperitoneal approach. This study aimed to determine the effect of prostate gland weight on the surgical and short-term oncological outcomes of RARP using the extraperitoneal approach. METHODS: In total, 1168 patients who underwent extraperitoneal RARP (EP-RARP) performed by a single surgeon at Yonsei University Severance Hospital between May 2009 and May 2016 were included in the study. The patients were divided into 4 groups according to the prostate weight measured by transrectal ultrasonography preoperatively. Intraoperative and postoperative outcomes were analyzed retrospectively. One-way analysis of variance and the chi-square test were used in the statistical analyses. RESULTS: Age, the Gleason score, clinical stage, and pathological stage were significantly different. Patients with a larger prostate size had a longer console time and higher estimated blood loss (P < 0.05). There were no significant differences between the 4 groups in length of hospital stay, duration of catheterization, blood transfusion, body mass index, prostate-specific antigen (PSA) level, history of abdominal surgery, intraoperative complications, positive surgical margin, incidence of lymphocele, and PSA recurrence after 1 year. CONCLUSIONS: The console time and estimated blood loss were significantly increased with a larger prostate size. However, there were no significant differences in the oncologic outcome and intraoperative complications, suggesting that EP-RARP requires meticulous bleeding control in patients with a prostate weighing > 75 g, and if appropriate management is implemented for blood loss intraoperatively, EP-RARP can be performed regardless of the prostate size.

Clinical significance and predictors of oncologic outcome after radical prostatectomy for invisible prostate cancer on multiparametric MRI.

BACKGROUND: The objective of our study was to evaluate the clinical significance of invisible prostate cancer (iPCa) on multiparametric magnetic resonance imaging (mpMRI) by analyzing clinical parameters and oncologic outcomes. METHODS: We retrospectively reviewed the records of patients treated with radical prostatectomy (RP) from 2010 to 2015 at our institution. Before RP, all patients were confirmed to have prostate cancer based on prostate biopsy. We excluded patients who underwent neoadjuvant therapy. Additionally, we excluded patients who had incomplete mpMRI based on PI-RADS (Prostate Imaging Reporting and Data System). iPCa was defined as having no grade 3 or higher region of interests using a scoring system established by PI-RADS without limitations on interpretation from mpMRI by radiologists. We selected patients with iPCa using this protocol. We analyzed data using univariate and multivariate cox regression analysis, logistic analysis, Kaplan-Meier curves, and receiver operator characteristic curves to predict biochemical recurrence (BCR). RESULTS: A total of 213 patients with iPCa were selected according to the patient selection protocol. Among them, pathological findings showed that Gleason score (GS) G6, G7 and ≥ G8 were present in 115 cases (54.0%), 78 cases (36.6%), and 20 cases (9.4%), respectively. Further, extracapsular extension (ECE), positive surgical margins (PSM), and lymphovascular invasion (LVI) were present in 28 (13.1%), 18 (8.5%), and 3 cases (1.4%), respectively. Seminal vesicle invasion (SVI) was observed in one case (0.5%). During a median follow-up time of 51 months, BCR was observed 29 cases. Adverse pathology (AP) was defined as GS ≥8, ECE, SVI and LVI. AP and prostate specific antigen (PSA) were significantly associated with BCR. Moreover, PSA > 6.2 ng/ml was suggested as a cut-off value for predicting BCR. CONCLUSIONS: In our results, cases of iPCa had clinically significant PCa, and AP and poor prognosis were also observed in some. Additionally, we found that PSA is the most clinically reliable predictor of oncologic outcome. We suggest that active treatment and diagnosis should be considered for patients with iPCa with PSA > 6.2 ng/ml.

Predictors of adverse pathologic features after radical prostatectomy in low-risk prostate cancer.

BACKGROUND: Prostate-specific antigen (PSA) screening more frequently detects early stage prostate cancer (PC). However, adverse pathologic features (APFs) after radical prostatectomy (RP) in low-risk PC occur. Previous related studies had utilized outdated staging criteria or small sample cohorts. In this study, we analyzed predictors of APFs after RP in low-risk PC using classification under the current criteria. MATERIALS AND METHODS: We retrospectively reviewed medical records of 546 low-risk PC patients who had undergone RP. Low-risk PC was defined as PC with clinical T1-T2a, Gleason score ≤ 6, and PSA levels < 10 ng/mL. Clinical and pathological parameters were analyzed to predict APFs. APFs were defined as extracapsular extension (ECE), seminal vesicle invasion (SVI), or positive surgical margins (PSM). We analyzed our data using univariable and multivariable logistic regression analyses, as well as receiver operator characteristics to predict APFs. RESULTS: Among 546 patients, ECE, SVI, and PSM were present in 199 (36.4%), 8 (1.5%), and 179 cases (32.8%), respectively. PSM had a significant correlation with preoperative high PSA levels and number of positive cores obtained. ECE/SVI was also significantly correlated with PSA levels and number of positive cores. As a result, presence of APFs after RP was associated with high PSA levels and large number of positive cores. PSA > 4.5 ng/mL and number of positive cores > 2 in low-risk PC were significantly associated with APFs, and suggested as cut-off values for predicting APFs. CONCLUSIONS: PSA > 4.5 ng/mL and number of positive cores > 2 in low-risk PC were associated with presence of APFs and patients with such records should be considered carefully to provide active surveillance.

Does robot-assisted radical prostatectomy benefit patients with prostate cancer and bone oligometastases?

OBJECTIVE: To investigate the peri-operative and oncological outcomes of robot-assisted radical prostatectomy (RARP) in patients with oligometastatic prostate cancer (PCa). PATIENTS AND METHODS: We retrospectively reviewed the records of 79 patients with oligometastatic PCa treated with RARP or androgen deprivation therapy (ADT) between 2005 and 2015 at our institution. Of these 79 patients, 38 were treated with RARP and 41 were treated with ADT without local therapy. Oligometastatic disease was defined as the presence of five or fewer hot spots detected by preoperative bone scan. We evaluated peri-operative outcomes, progression-free survival (PFS), and cancer-specific survival (CSS). We analysed data using Kaplan-Meier methods, with log-rank tests and multivariate Cox regression models. RESULTS: Patients treated with RARP experienced similar postoperative complications to those previously reported in RP-treated patients, and fewer urinary complications than ADT-treated patients. PFS and CSS were longer in RARP-treated compared with ADT-treated patients (median PFS: 75 vs 28 months, P = 0.008; median CSS: not reached vs 40 months, P = 0.002). Multivariate analysis further identified RARP as a significant predictor of PFS and CSS (PFS: hazard ratio [HR] 0.388, P = 0.003; CSS: HR 0.264, P = 0.004). CONCLUSIONS: We showed that RARP in the setting of oligometastatic PCa is a safe and feasible procedure which improves oncological outcomes in terms of PFS and CSS. In addition, our data suggest that RARP effectively prevents urinary tract complications from PCa. The study highlights results from expert surgeons and highly selected patients that cannot be extrapolated to all patients with oligometastatic PCa; to confirm our findings, large, prospective, multicentre studies are required.

Prognostic Significance of the Proportion of Ductal Component in Ductal Adenocarcinoma of the Prostate.

PURPOSE: In prostate cancer ductal adenocarcinoma is mixed with the usual acinar adenocarcinoma. However, to our knowledge whether the proportion of the ductal component affects oncologic outcomes is currently unknown. We investigated whether the proportion of the ductal component predicts oncologic outcomes in ductal adenocarcinoma. MATERIALS AND METHODS: We retrospectively reviewed clinical data on 3,038 patients with prostate cancer who underwent radical prostatectomy at our institution between 2005 and 2014. We excluded patients who received neoadjuvant or adjuvant treatment. Patients were stratified based on the proportion of the ductal component. We compared the probability of biochemical recurrence between groups and investigated how the proportion of the ductal component influences biochemical recurrence using Kaplan-Meier estimates and Cox regression models, respectively. RESULTS: Of 2,648 patients 101 (3.8%) had ductal adenocarcinoma and 2,547 (96.2%) had acinar adenocarcinoma. Freedom from biochemical recurrence in patients with ductal adenocarcinoma was significantly lower than in those with acinar adenocarcinoma (p <0.001). When ductal cases were stratified by the proportion of the ductal component, freedom from biochemical recurrence in the high ductal component group was significantly lower compared to that in the low ductal component group (30% or greater vs less than 30%, p = 0.023). On univariate and multivariate Cox regression analyses, a high ductal component was a significant predictor of biochemical recurrence (p <0.001). CONCLUSIONS: The prognosis for ductal adenocarcinoma can be stratified by the proportion of the ductal component. This marker could potentially be used as a surrogate for poor prognosis or as a determinant for adjuvant therapy.

Prognostic Significance of Vas Deferens Invasion After Radical Prostatectomy in Patients with Pathological Stage T3b Prostate Cancer.

BACKGROUND: Seminal vesicle invasion (SVI) is associated with adverse clinical outcomes in prostate cancer (PCa) patients. Despite its anatomical similarity and close proximity to the seminal vesicle, the prognostic significance of vas deferens invasion (VDI) by PCa has not been elucidated. For these reasons, we investigated the impact of VDI on the oncological outcome of pT3b PCa in association with SVI. METHODS: We retrospectively reviewed the medical records of 3359 patients who had undergone a radical prostatectomy at our institution between January 2000 and December 2014 for PCa. Patients who received neoadjuvant or adjuvant treatment (radiation, androgen deprivation therapy, or both) and those without adequate medical records were excluded. A Kaplan-Meier analysis was performed to analyze biochemical recurrence-free survival (BCRFS), and a Cox regression model was used to test the influence of VDI on biochemical recurrence (BCR). RESULTS: Of 350 patients with pathologically confirmed SVI (pT3b), 87 (24.9%) had VDI, while the remaining 263 patients (75.1%) had isolated SVI. Compared with SVI patients without VDI, SVI patients with VDI were noted to have a significantly worse 5-year BCRFS (25.1 vs. 17.1%, respectively). VDI was a significant predictor of BCR in multivariate Cox regression analysis (hazard ratio 1.39, 95% confidence interval 1.02-1.90; p = 0.039). CONCLUSIONS: Our results shows that the prognosis of PCa with SVI might be further stratified by VDI status, thus suggesting the role of VDI either as a surrogate for poor prognosis or as a determinant for adjuvant therapy.

Intermediate PSA half-life after neoadjuvant hormone therapy predicts reduced risk of castration-resistant prostate cancer development after radical prostatectomy.

BACKGROUND: The magnitude and rapidity of the tumor response to androgen deprivation is known to predict the durability of the therapy. We have investigated the predictive value of categorizing patients by the half-life of PSA under neoadjuvant androgen deprivation therapy in patients with biochemical recurrence after radical prostatectomy. METHODS: Medical records of 317 patients who received neoadjuvant androgen deprivation therapy before radical prostatectomy and developed biochemical recurrence were analyzed. The patients were categorized into five groups according to PSA half-life. Risk of developing castration resistance was evaluated by Kaplan-Meier analysis and by Cox proportional risk regression analysis. RESULTS: The median follow-up duration was 50.1 months (IQR 31.8-68.7) and median PSA half-life was 22.1 days (IQR 12.7-38.4). Comparison of survival curves revealed that patients in the intermediate response group showed significantly lower 5-year castration-resistant prostate cancer rate (37.5%) compared to non-response and ultra-rapid response groups (63.6%, p = 0.007; 56.1%, p = 0.031; respectively). In the multivariate regression model, intermediate response compared to non-response was associated with significantly reduced risk of castration resistance development (hazard ratio 0.397, 95% confidence interval 0.191-0.823, p = 0.013) and overall mortality (hazard ratio 0.138, 95% confidence interval 0.033-0.584, p = 0.007). When subcategorized by Gleason score, Kaplan-Meier curve revealed that, in the high Gleason score stratum, 5-year castration-resistant prostate cancer rate for intermediate response group (44.0%) was exceptionally lower than that in non-response group (66.7%, p = 0.047), while castration resistance increased in other groups. CONCLUSION: Short PSA half-life as well as no response after androgen deprivation is associated with increased risk of treatment failure compared to intermediate PSA half-life.

Impact of lymphovascular invasion on lymph node metastasis for patients undergoing radical prostatectomy with negative resection margin.

BACKGROUND: The association between lymphovascular invasion and lymphatic or hematogenous metastasis has been suspected, with conflicting evidence. We have investigated the association between the risk of biochemical recurrence and lymphovascular invasion in resection margin negative patients, as well as its association with lymph node metastasis. METHODS: One thousand six hundred thirty four patients who underwent radical prostatectomy from 2005 to 2014 were selected. Patients with bone or distant organ metastasis at the time of operation were excluded. Survival analysis was performed to assess biochemical recurrence, metastasis and mortality risks by Kaplan-Meier analysis and multivariate Cox proportional hazard regression. Odds of lymph node metastasis were evaluated by Logistic regression. RESULTS: LVI was detected in 118 (7.4%) patients. The median follow-up duration was 33.1 months. In the Kaplan-Meier analysis, lymphovascular invasion was associated with significantly increased 5-year and 10-year BCR rate (60.2% vs. 39.1%, 60.2% vs. 40.1%, respectively; p < 0.001), 10-year bone metastasis rate and cancer specific mortality (16.9% vs. 5.1%, p = 0.001; 6.8% vs. 2.7%, p = 0.034, respectively) compared to patients without LVI. When stratified by T stage and resection margin status, lymphovascular invasion resulted in significantly increased 10-year biochemical recurrence rate in T3 patients both with and without positive surgical margin (p = 0.008, 0.005, respectively). In the multivariate Cox regression model lymphovascular invasion resulted in 1.4-fold BCR risk and 1.7-fold metastasis risk increase (95% CI 1.045-1.749, 1.024-2.950; p = 0.022, 0.040, respectively). Lymphovascular invasion was revealed to be strongly associated with lymph node metastasis in the multivariate Logistic regression (OR 4.317, 95% CI 2.092-8.910, p < 0.001). CONCLUSION: Lymphovascular invasion increases the risk of recurrence in T3 patients regardless of margin status, by accelerating lymph node metastasis and distant organ metastasis.

Corrigendum: Radical prostatectomy versus radiotherapy as local therapy for primary tumors in patients with oligometastatic prostate cancer.

[This corrects the article DOI: 10.3389/fonc.2024.1368926.].

Radical prostatectomy versus radiotherapy as local therapy for primary tumors in patients with oligometastatic prostate cancer.

Introduction: We compared radical prostatectomy (RP) and radiotherapy (RT) as local therapies for primary tumors and examined their associations with survival outcomes and urinary tract complications in patients with oligometastatic prostate cancer (omPC). Methods: We evaluated the data of 85 patients diagnosed with omPC who underwent local therapy for primary tumors between January 2008 and December 2018. Of the 85 patients, 31 underwent prostate RT, while 54 underwent RP. Oligometastatic disease was defined as the presence of fewer than five metastatic lesions without visceral metastasis. Urinary tract complications, progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS) were evaluated using the Kaplan-Meier method and Cox regression analyses. Results: Patients treated with RT showed higher prostate-specific antigen levels. There was no significant difference in the 5-year PFS (52.5% vs. 37.9%, p=0.351), CSS (67.6% vs. 84.7%, p=0.473), or OS (63.6% vs. 73.8%, p=0.897) between the RT and RP groups. In the multivariate analyses, the type of local therapy was not associated with PFS (hazard ratio [HR]=1.334, p=0.356), CSS (HR=0.744, p=0.475), or OS (HR=0.953, p=0.897). Conclusion: Therefore, RP seems to be a possible treatment option for patients with omPC, exhibiting oncologic outcomes comparable to those with RT.

Risks of Dementia After Treatment with an Anticholinergic, Beta-3 Agonist, or Combination of Both for an Overactive Bladder: A Korean National Cohort Study.

BACKGROUND AND OBJECTIVE: An overactive bladder (OAB) is primarily managed with behavioural therapy and using anticholinergics and beta-3 agonists. Reports have shown that the use of anticholinergics by OAB patients was associated with an increased risk of new-onset dementia compared with those using beta-3 agonists. This study compares the risks of dementia among patients with an OAB starting on a beta-3 agonist alone, an anticholinergic alone, or a combination treatment. METHODS: Using data from the Korean National Health Insurance Service database, we studied a nationwide population cohort comprising patients newly diagnosed with an OAB who initiated their OAB medications between 2015 and 2020. The treatment types were categorised as anticholinergics (oxybutynin, solifenacin, tolterodine, trospium, fesoterodine, flavoxate, and propiverine) alone, a beta-3 agonist (mirabegron) alone, and combination therapy (an anticholinergic plus the beta-3 agonist). To evaluate the impact of cumulative drug exposure, we quantified the cumulative exposure to solifenacin and mirabegron as cumulative defined daily doses (cDDDs) using proportional hazards regression analyses, adjusted for factors known to be associated with dementia. KEY FINDINGS AND LIMITATIONS: Among the study's 3 452 705 patients, 671 974 were new users of a beta-3 agonist alone (19.5%), 1 943 414 new users of anticholinergics alone (56.3%), and 837 317 receiving combination therapy (24.3%). The most common anticholinergic used both alone and as part of a combination treatment was solifenacin (42.9% and 56.3%, respectively). There was an increased risk of dementia between the users of an anticholinergic alone (adjusted hazard ratio [aHR] = 1.213; 95% confidence interval [CI], 1.195-1.232) and those taking a combination treatment (aHR = 1.345; 95% CI, 1.323-1.366) compared with the users of beta-3 agonists alone after the adjustment of covariates. However, the incidence of dementia was also significantly higher, with an increase in the cumulative dose of mirabegron (aHR = 1.062 [1.021-1.106] for 28-120 cDDDs and aHR = 1.044 [1.004-1.084)] for patients who received >121 cDDDs compared with those who received <27 cDDDs). A marked increased risk of dementia was associated with the use of solifenacin, tolterodine, fesoterodine, and propiverine, both separately and in combination with mirabegron. CONCLUSIONS AND CLINICAL IMPLICATIONS: In this large Korean cohort, the use of anticholinergics with or without a beta-3 agonist increased the risk of new-onset dementia compared with the use of a beta-3 agonist alone. Given that the risk of dementia was most significantly elevated with combination treatments, care should be taken when considering combination treatment for OAB patients with risk factors for dementia. Furthermore, there could be a possible association between beta-3 agonists and dementia, although future studies are needed. PATIENT SUMMARY: This study investigated the risk of dementia induced by overactive bladder (OAB) treatment in a large Korean cohort. Two representative OAB treatment drugs, anticholinergics and beta-3 agonists, both increased the risk of new-onset dementia. Clinicians should be cautious in using OAB treatment drugs since no drugs could be concluded as safe.