Efficacy of the Addition of Robot-assisted Radical Cystectomy with Extracorporeal Urinary Diversion after an Enhanced Recovery Protocol.

PURPOSE: It is unclear if robotic radical cystectomy with extracorporeal urinary diversion (eRARC) provides additional benefit when performed along with enhanced recovery after surgery (ERAS). We assessed the additional efficacy of eRARC in terms of perioperative outcomes. MATERIALS AND METHODS: We retrospectively assessed 143 patients undergoing radical cystectomy with urinary diversion between June 2010 and December 2021 at a single center. The patients were assigned to three groups: open radical cystectomy (ORC) with conventional recovery after surgery (CRAS) [Group A], ORC with ERAS [Group B], and eRARC with ERAS [Group C]. A propensity score-matched analysis was performed to evaluate how ERAS and eRARC affected outcomes respectively. Meanwhile, multivariable analysis was used to detect the predictors of prolonged length of hospital stay (LOS). RESULTS: The median LOS was shorter after ERAS and eRARC. In the propensity score-matched analysis, ERAS was linked to a significantly shorter median LOS (28.0 vs. 20.0 days, P < .001), but eRARC was not associated with a shorter LOS (19.0 vs. 17.5 days, P = .21). Neither ERAS nor eRARC were connected with a reduce in complication rate. Following multivariable analysis, ERAS was found to be independently associated with shorter LOS (OR=0.23, P < .001), but eRARC demonstrated no such correlation (OR=0.29, P = .096). CONCLUSION: ERAS had strong association with shorter LOS, although eRARC did not contribute to additional efficacy. Neither ERAS nor eRARC decreased the complication rate.

Impact of the coronavirus disease 2019 pandemic on the number of undergoing radical nephroureterectomy and postoperative adjuvant systematic therapy for upper tract urothelial carcinomas in Japan: A multicenter retrospective study.

OBJECTIVES: The coronavirus disease 2019 pandemic has affected cancer management worldwide. For upper tract urothelial carcinomas, delays in treatments are not recommended even during the pandemic. We investigated the impact of the pandemic on patients with these carcinomas who underwent radical nephroureterectomy (RNU) and adjuvant systematic therapy before and after COVID-19 spread in Japan. METHODS: This multicenter retrospective study included 304 patients who underwent RNU for upper tract urothelial carcinomas between May 1, 2019, and December 31, 2021, in Aichi, Japan. The patients were categorized into three groups based on whether they underwent surgery in the prepandemic (before infection spread in Japan), early pandemic (between confirmation of the first case and vaccination initiation), and late pandemic (after the start of vaccination in Japan) phases. The patient characteristics, diagnostic methods, pathological findings, and postoperative therapy were compared among the three phases. RESULTS: Overall, 74, 152, and 78 patients underwent RNU in the prepandemic, early pandemic, and late pandemic phases, respectively. The number of patients who underwent preoperative ureteroscopy decreased significantly from the prepandemic phase to the late pandemic phase due to pandemic-related restrictions (p = 0.016). There was no difference in the time to the first visit or pathological findings. Among patients classified as high-risk according to existing clinical trials, the proportion receiving adjuvant systematic therapy after RNU decreased significantly from 52.3% to 19% (p = 0.003). CONCLUSIONS: There was no difference in the pathological findings. The number of patients receiving appropriate adjuvant systematic therapy decreased during the pandemic.

Clinical utility of intraductal carcinoma of the prostate in treatment selection for metastatic hormone-sensitive prostate cancer.

BACKGROUND: In recent years, the usefulness of androgen receptor axis-targeted agents (ARATs) such as abiraterone, enzalutamide, and apalutamide for the upfront treatment of metastatic hormone-sensitive prostate cancer (mHSPC) has been demonstrated. However, it remains unclear which patients would truly benefit from these treatments. Furthermore, intraductal carcinoma of the prostate (IDC-P) is a known poor prognostic factor in patients with prostate cancer. We investigated the association between the presence of IDC-P and response to therapy in patients with mHSPC. METHODS: This retrospective analysis included 318 patients with mHSPC who received treatment at Nagoya University and its 12 affiliated institutions between 2014 and 2021. Their biopsy specimens were evaluated for the presence of IDC-P. The patients were classified according to their first-line treatment into the ARAT (n = 100, receiving a combination of androgen-deprivation therapy [ADT] and ARAT) or conventional therapy (n = 218, receiving ADT with or without standard antiandrogen agents) group. We compared the overall survival (OS) and second progression-free survival (PFS2) between the ARAT and conventional groups according to the presence of IDC-P to evaluate whether presence of IDC-P predicts the response to each treatment. PFS2 was defined as the period from mHSPC diagnosis to disease progression on second-line treatment or death. Propensity score matching with one-to-one nearest-neighbor matching was used to minimize the potential effects of selection bias and confounding factors. The clinicopathological variables of the patients were well-balanced after propensity score matching. RESULTS: Most patients in the ARAT (79%) and conventional therapy (71%) groups were ICD-P positive. In the propensity score-matched cohort, the OS and PFS2 of IDC-P-positive patients were significantly longer in the ARAT group than in the conventional group (OS: hazard ratio [HR], 0.36; p = 0.047; PFS2: HR, 0.30; p < 0.001). In contrast, no difference in OS and PFS2 was observed between the ARAT and conventional groups in IDC-P-negative patients (OS: HR, 1.09; p = 0.920; PFS2: HR, 0.40; p = 0.264). CONCLUSIONS: The findings highlight a high prevalence of IDC-P among patients with mHSPC and suggest that IDC-P positivity may be a reliable indicator that ARAT should be implemented as first-line treatment.

A case of metastatic prostate cancer treated with metastasectomy.

In general, metastatic prostate cancer is managed medically. Here we present a patient with metastatic prostate cancer who was treated by surgical resection in addition to medical therapies. Local therapies should be considered if metastatic lesions are limited, also in cases of metastatic prostate cancer.

The clinical benefit of sequential therapy with androgen receptor axis-targeted agents alone in patients with castration-resistant prostate cancer: A propensity score-matched comparison study.

BACKGROUND: The optimal sequential therapy for castration-resistant prostate cancer (CRPC) remains unknown. In recent years, some doubts have emerged regarding the clinical benefit of sequential therapy with androgen receptor axis-targeted agents (ART) such as abiraterone (ABI) or enzalutamide (ENZ) for patients with CRPC. We compared the effect of ART-to-ART (AA) sequential therapy after castration resistance with that of docetaxel (DTX)-combined sequential therapy (ART to DTX or DTX to ART) in patients with CRPC. METHODS: We retrospectively identified and analyzed the data of 315 patients with CRPC treated in our seven affiliated institutions between 2009 and 2019. All patients received either DTX or ART (ABI or ENZ) as the first- or second-line therapy after castration resistance. We compared the overall survival (OS) and the second progression-free survival (PFS2), calculated from the initiation of first-line therapy after castration resistance, between the AA sequence group and the DTX-combined sequence group. PFS2 was defined as the period from the start of first-line treatment after castration resistance to progression on second-line treatment. To minimize selection bias from possible confounders, we performed propensity score matching using one-to-one nearest neighbor matching without replacement. RESULTS: Overall, 106 and 209 patients were administered the AA sequential therapy and DTX-combined sequential therapy, respectively. The clinicopathological variables of patients were well balanced after propensity score matching, and there were no significant differences between the two groups. In the propensity score-matched cohort, OS was not significantly different between the two groups (median, 37.9 vs. 45.4 months; hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.68-1.79; p = .701), while PFS2 was significantly shorter in the AA group than in the DTX-combined group (median, 12.9 vs. 21.6 months; HR, 1.70; 95% CI, 1.16-2.48; p = .007). CONCLUSIONS: Certain patients with CRPC can benefit from ART-to-ART sequential therapy in a daily clinical setting.

Effect of core needle biopsy number on intraductal carcinoma of the prostate (IDC-P) diagnosis in patients with metastatic hormone-sensitive prostate cancer.

BACKGROUND: The number of core needle biopsies in metastatic prostate cancer cases are sometimes reduced to avoid various complications. We analyzed whether core needle biopsy number influence IDC-P detection rate in patients with metastatic castration-sensitive prostate cancer (mHSPC). METHODS: We retrospectively evaluated data from 150 patients diagnosed with mHSPC. Subjects were allocated to three groups according to the number of core biopsies performed: ≤ 5, 6-9, and ≥ 10. The study endpoints were the cancer-specific survival (CSS) and overall survival (OS) rates. RESULTS: For patients who underwent ≥ 10 core biopsies, a significant difference on CSS was detected between with or without IDC-P (P = 0.016). On the other hand, the difference decreased as the number of core biopsies became smaller (6-9; P = 0.322 and ≤ 5; P = 0.815). A similar trend was identified for the OS outcome. A significant difference on OS was also found between with or without IDC-P in patients who underwent ≥ 10 and 6-9 core needle biopsies (P = 0.0002 and 0.017, respectively), but not in those who underwent ≤ 5 core biopsies (P = 0.341). IDC-P served as a stronger prognostic marker for CSS and OS than did the other factors included in the multivariate analysis for patients had ≥ 10 core biopsies (P = 0.016, and P = 0.0014, respectively). CONCLUSIONS: Given the IDC-P detection and its value as a prognostic marker, we propose the performance of ≥ 10 core biopsy procedures in patients diagnosed with mHSPC to minimize the sampling error of the IDC-P.

[ADOPTION OF ENHANCED RECOVERY AFTER SURGERY (ERAS) PROTOCOL FOR THE MANAGEMENT OF PATIENTS UNDERGOING RADICAL CYSTECTOMY IN JAPAN].

(Objectives) The Enhanced Recovery After Surgery (ERAS) protocols are standardized and multimodal perioperative care pathways designed to improve surgical outcomes by minimizing stress response and inflammation following surgery. First adopted in colorectal surgery, ERAS is now being employed in various other types of surgeries, most recently in patients undergoing radical cystectomy (RC). Implementation of ERAS protocols resulted in reductions in perioperative complication rates and length of hospital stay (LOS). However, information on the adoption of ERAS in patients undergoing RC in Japan is limited. The objective of this study was to evaluate the safety and efficacy of ERAS implemented in the Toyohashi Municipal Hospital in 2017 for the management of patients with RC. (Patients and methods) This was a retrospective study of 103 patients who underwent RC and urinary diversion from January 2012 to March 2019. Of the 103 patients, 71 underwent surgery prior to the introduction of the ERAS were allocated to the 'traditional' group, while 32 were exposed to the ERAS protocol were allocated to the 'ERAS' group. In this study, ERAS included no bowel preparation, preoperative carbohydrate loading, preoperative fluid reduction, preoperative fasting, reduced drainage use, no nasogastric intubation, and early postoperative drinking and eating. A comparative analysis was performed to evaluate LOS and postoperative complication rate (Clavien classification ≥2) after RC between the 'traditional' and 'ERAS' groups. (Results) Patient characteristics and intraoperative variables such as median age, sex, body mass index, clinical and pathological cancer stage, amount of bleeding, need for transfusion, and technique of urinary diversion did not differ between groups. However, duration of surgery was significantly shorter in the ERAS group than in the traditional group (402 min vs. 470 min; P = 0.03). Further, rate of complication was significantly lower (43.8% vs. 67.6%; P=0.03) and LOS after RC was significantly shorter (21 days vs. 28 days; P<0.001) in the ERAS group compared to the traditional group. Moreover, ERAS was an independent factor affecting shorter LOS after RC (OR, 5.22; 95% CI, 1.52-17.90; P = 0.009) in multivariate analyses. (Conclusions) It is possible that the ERAS protocol adopted in this study reduced the LOS and postoperative complication rate after RC at this site in Japan.

Response of intraductal carcinoma of the prostate to androgen deprivation therapy predicts prostate cancer prognosis in radical prostatectomy patients.

BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) has a poor prognosis and is thought to be completely resistant to current therapies, including androgen deprivation therapy (ADT). However, to date, there are no data showing direct evidence of such resistance. METHODS: We retrospectively evaluated 145 patients with high-risk prostate cancer who underwent radical prostatectomy (RP) with neoadjuvant ADT between 1991 and 2005. All patient data were collected from slides prepared from needle biopsy (NB) samples of prostate tissue and RP specimens. Data were analyzed in terms of serum level of prostate specific antigen (PSA), Gleason score of NB samples, clinical T stage, the positive cancer core rate, maximum cancer extension rate, presence of Gleason pattern 5, and presence of IDC-P in both NB samples and RP specimens. RESULTS: The median initial PSA was 33.2 ng/mL (range, 2.4-296 ng/mL), and the median follow-up period was 109 months (range, 11-257 months). The preoperative median ADT period was 4 months (range, 1-20 months). IDC-P was present in 53 patients (37%) in NB samples and 65 (45%) in RP. The patients were divided into three groups based on the presence or absence of IDC-P in NB/RP samples (IDC-P-negative at biopsy: 92 cases, IDC-P-positive at biopsy with IDC-P disappearance: 15 cases, and IDC-P-positive at biopsy with IDC-P persistence: 38 cases). Overall, 28% of IDC-P-positive cases in NB samples showed the disappearance of IDC-P at RP. IDC-P persistence cases showed the poorest prognosis, while IDC-P disappearance cases had a similar prognosis to that of IDC-P-negative at biopsy cases in terms of disease-free survival, cancer-specific survival, and overall survival (P = .0018, P = .0087, and P = .0034, respectively). CONCLUSIONS: Some cases with IDC-P responded to ADT and demonstrated favorable clinical outcomes similar to those of cases without IDC-P. These findings indicate that cases with IDC-P are heterogeneous.

Propensity score-matched comparison of docetaxel and androgen receptor axis-targeted agents in patients with castration-resistant intraductal carcinoma of the prostate.

OBJECTIVE: To evaluate the efficacy of docetaxel and androgen receptor axis-targeted (ARAT) agents in patients with castration-resistant prostate cancer (CRPC) with intraductal carcinoma of the prostate (IDC-P) using a propensity score-matched analysis. PATIENTS AND METHODS: We retrospectively identified 309 patients with CRPC from February 2007 to February 2016 at Nagoya University and its affiliated hospitals. All patients received initial androgen-deprivation therapy (ADT). After progression to CRPC, they received docetaxel or ARAT (abiraterone or enzalutamide) as first-line life-prolonging therapy. Docetaxel (70-75 mg/m2 ) every 3 weeks vs enzalutamide (160 mg) once daily orally or abiraterone (1 g) once daily plus prednisone (5 mg) twice daily orally was administered. The primary outcome of interest was overall survival (OS) from the time of CRPC diagnosis. A propensity score analysis with a 1:1 ratio using an optimal matching algorithm was used to adjust for confounding factors. RESULTS: Overall, 234 patients were analysed. Propensity score-matching identified 85 patients in each group. There were no significant differences in patient characteristics between the groups. The median OS in the docetaxel group was 38.2 vs 58.3 months in the ARAT group (P = 0.03). For patients with IDC-P, OS was significantly longer in the ARAT group than the docetaxel group (P = 0.01), and there was no significant difference in each group, as in patients without IDC-P (P = 0.67). A multivariate analysis showed that the presence of IDC-P, duration of primary ADT, visceral metastasis, and administration of ARAT as the first-line treatment for CRPC were independent prognostic factors for OS. CONCLUSION: Administration of ARAT as the first-line treatment for CRPC may prolong OS more than that of docetaxel, especially in patients with IDC-P.

A case of advanced prostate cancer controlled for the long term by flutamide after bicalutamide failure.

Currently, the early introduction of new antiandrogens is popular for castration-resistant prostate cancer (CRPC). However, adverse events can be severe and their costs are high. Here, we present a patient with CRPC in whom flutamide controlled disease progression for 10 years. This case report shows that conventional alternative antiandrogens are cost effective and are still an important option for the treatment for CRPC.

The influence of the presence of intraductal carcinoma of the prostate on the grade group system's prognostic performance.

BACKGROUND: Although the presence of intraductal carcinoma of the prostate (IDC-P) influences biochemical failure in radical prostatectomy patients, no data are available regarding the impact of its integration into the classification grade group system. Thus, the aim of this study was to enhance the utility of the grade group system by integrating the presence of IDC-P. METHODS: This study was a retrospective evaluation of 1019 patients with prostate cancer who underwent radical prostatectomy between 2005 and 2013 without neoadjuvant or adjuvant therapy. The data on age, prostate-specific antigen (PSA) level at diagnosis, pathological T stage (pT), presence of Gleason pattern 5 (GP5), presence of IDC-P, and surgical margin status were analyzed to predict PSA recurrence after prostatectomy. RESULTS: The median patient age was 67 (range, 45-80) years and the median initial PSA level was 6.8 (range, 0.4-82) ng/mL. The median follow-up period was 82 (range, 0.7-148) months. IDC-P was detected in 157 patients (15.4%). Among these patients, the increase in the positive rate of IDC-P correlated with tumor upgrading. The grade groups (GGs) were as follows: GG1 without IDC-P, 16.0% (n = 163); GG2 without IDC-P, 46.1% (n = 470); GG3 without IDC-P, 15.7% (n = 160); GG4 without IDC-P, 2.6% (n = 27); GG5 without IDC-P, 4.1% (n = 42); any GG with IDC-P, 15.4% [n = 157; GG 2 (n = 29); GG3 (n = 60); GG4 (n = 13); GG5 (n = 55)]. Any grade Group with IDC-P showed significantly worse prognosis than any other group without IDC-P (P < 0.0001). In a multivariate analysis, integration of the IDC-P into the Grade Groups, the PSA level at diagnosis, and the surgical margin status were significant prognostic predictors (P < 0.0001, < 0.0001 and < 0.0001, respectively). CONCLUSIONS: Integrating the presence of IDC-P into the grade group system will result in more accurate predictions of patient outcome.

Efficacy of zoledronic acid in older prostate cancer patients undergoing androgen deprivation therapy.

OBJECTIVES: The purpose of this study is to evaluate the efficacy of annual zoledronic acid treatment in Japanese patients with nonmetastatic prostate cancer during androgen deprivation therapy (ADT). METHODS: This is a single institution 12-month study. Between 2016 and 2019, patients aged 70 years or older on ADT for nonmetastatic prostate cancer had bone mineral density (BMD) measured and 10-year probability of fracture calculated using fracture risk assessment tool (FRAX). Patients who showed osteopenia or had a 10-year hip fracture risk ≥ 3% or a 10-year probability of major osteoporotic fracture ≥ 20% were offered treatment with zoledronic acid 5 mg intravenously (ZA group). The patients who did not receive treatment were set as the control group. Lumbar and hip BMD were measured 6 and 12 months after treatment in the ZA group and 12 months after baseline in the control group. The yearly BMD change of both groups was compared. RESULTS: The mean ages of the ZA group (n = 26) and control group (n = 12) were 80.5 ± 9.1 and 76.1 ± 6.7 years, respectively. In the ZA group, lumbar and hip BMD changes at 12 months were +2.1% and +0.8%, respectively. In the control group, lumbar and hip BMD changes were -0.9% and -4.9%, respectively. There were statistically significant differences between the 2 groups in BMD percent changes (P < 0.05). CONCLUSIONS: Without intervention, BMD tends to continue to decrease during ADT. Our findings suggest that administration of zoledronic acid enables maintenance of BMD in the older adults.

Integrating tertiary Gleason pattern 5 into the ISUP grading system improves prediction of biochemical recurrence in radical prostatectomy patients.

Although the presence of tertiary Gleason pattern 5 is reportedly related to unfavorable prostate cancer characteristics, few data are available regarding the effects of tertiary Gleason pattern 5 on the new ISUP (International Society of Urological Pathology) grading system in radical prostatectomy patients. In this study, we evaluated the effect of tertiary Gleason pattern 5 on biochemical recurrence following radical prostatectomy in patients with prostate cancer. We retrospectively evaluated 1000 patients with prostate cancer who underwent radical prostatectomy. The ISUP Grades were as follows: Grade 1, 16.3%; Grade 2, 48.1% (with tertiary Gleason pattern 5, 8.0% and without tertiary Gleason pattern 5, 40.1%); Grade 3, 21.9% (with tertiary Gleason pattern 5, 9.1% and without tertiary Gleason pattern 5, 12.8%); Grade 4, 3.9%; and Grade 5, 9.8%. Biochemical recurrence-free survival differed significantly among the five groups (Grade 1-5) (P < 0.0001). Grade 2 with tertiary Gleason pattern 5 had a significantly worse prognosis than Grade 2 without tertiary Gleason pattern 5. Similarly, Grade 3 with tertiary Gleason pattern 5 demonstrated a significantly worse prognosis than Grade 3 without tertiary Gleason pattern 5. When Grade 2 and Grade 3 were divided with or without tertiary Gleason pattern 5, the survival curves differed significantly among Grade 1, Grade 2 without tertiary Gleason pattern 5, Grade 2 with tertiary Gleason pattern 5, Grade 3 without tertiary Gleason pattern 5, Grade 3 with tertiary Gleason pattern 5, and Grade 4 (P < 0.0001) (hazard ratios: 1, 1.14, 1.86, 2.23, 3.53, and 6.30). In a multivariate analysis, integrating tertiary Gleason pattern 5 into the ISUP Grade, PSA, and surgical margin status significantly predicted biochemical recurrence (P < 0.0001). Integrating tertiary Gleason pattern 5 into the ISUP grading system will improve the accuracy of patient outcome prediction following radical prostatectomy in patients with prostate cancer.

Efficacy of docetaxel in castration-resistant prostate cancer patients with intraductal carcinoma of the prostate.

BACKGROUND: This study aimed to investigate the efficacy of docetaxel in castration-resistant prostate cancer (CRPC) patients with intraductal carcinoma of the prostate (IDC-P). PATIENTS AND METHODS: We retrospectively identified 79 CRPC patients with distant metastasis at initial diagnosis from June 2002 to January 2014. All patients received initial androgen deprivation therapy and 46 received docetaxel chemotherapy after progressing to CRPC. The primary outcome of interest was cancer-specific survival (CSS) from the time of CRPC diagnosis. The Cox regression model was used to confirm whether IDC-P and docetaxel would act as independent factors for prognosis. RESULTS: IDC-P was found in 62 of 79 patients. The median CSS in the IDC-P-present group was 18.2 versus 45.6 months in the IDC-P-absent group (HR 2.67; 95% CI 1.18 to 6.06; P = 0.019). Docetaxel was administered to 36 patients with IDC-P and 10 patients without IDC-P, with a median CSS of 20.5 versus 53.2 months, respectively (HR 2.98; 95% CI 1.02 to 8.64; P = 0.044). Multivariate analysis demonstrated that the presence of IDC-P and docetaxel were independent prognostic factors for CSS (P = 0.026 and 0.005, respectively) and overall survival (OS) (P = 0.029 and 0.001, respectively). CONCLUSION: The presence of IDC-P is an independent prognostic factor in CRPC patients with distant metastases and IDC-P in needle biopsies at the time of initial diagnosis. Docetaxel may prolong CSS and OS in CRPC patients with distant metastases and IDC-P in needle biopsies at the time of initial diagnosis.