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Language：English   Publisher：John Wiley & Sons Australia, Ltd  

Language：English   Publisher：The Prostate  

BACKGROUND: Proton pump inhibitors (PPIs) are widely used due to their affordability and minimal severe side effects. However, their influence on the efficacy of cancer treatments, particularly androgen receptor signaling inhibitors (ARSIs), remains unclear. This study investigates the impact of PPI usage on the treatment outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: A total of 117 mCRPC patients were retrospectively analyzed and divided into two groups based on the concomitant use of PPI at the initiation of ARSI treatment: PPI+ (n = 38) and PPI- (n = 79). Patient characteristics, including age at ARSI treatment administered, prostate-specific antigen (PSA) value at ARSI treatment administered, International Society of Urological Pathology grade group at prostate biopsy, metastatic site at ARSI treatment administered, prior docetaxel (DTX) treatment, and type of ARSI (abiraterone acetate or enzalutamide) were recorded. Progression-free survival (PFS), overall survival (OS), and PSA response rates were compared between the two groups. Patients were further stratified by clinical background to compare PFS and OS between the two groups. RESULTS: The PPI- group exhibited significantly extended PFS and a trend toward improved OS. For PSA response (reduction of 50% or more from baseline), the rates were 62.3% and 45.9% in the PPI- group and the PPI+ group, respectively. For deep PSA response (reductions of 90% or more from baseline), the rates were 36.4% and 24.3% in the PPI- group and the PPI+ group, respectively. The effects were consistent across subgroups divided by prior DTX treatment and type of ARSI administered. CONCLUSIONS: The administration of PPIs appears to diminish the therapeutic efficacy of ARSIs in mCRPC patients. Further prospective studies are needed to confirm these findings and explore the biological mechanisms involved.

DOI： 10.1002/pros.24769

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Language：English   Publisher：Annals of surgical oncology  

BACKGROUND: This study aimed to show the association between tumor location and laterality of positive lymph nodes by evaluating biopsy and magnetic resonance imaging (MRI) findings, and to optimize the extended pelvic lymph node dissection (ePLND) side for prostate cancer. METHODS: The study enrolled patients who underwent robot-assisted radical prostatectomy with ePLND. Tumor locations were determined according to International Society of Urological Pathology grade group 4/5 in biopsies and Prostate Imaging-Reporting and Data System category 4/5 in MRI results. The concordance of tumor location lobe and positive lymph node side with the performance of tumor location-guided ePLND for positive lymph node detection was evaluated. RESULTS: For 301 patients who underwent ePLND at Kyushu University Hospital, tumor locations determined by biopsy and MRI findings showed no lesion in 8 (2.7%) patients, unilateral lobe in 223 (74.1%) patients, and bilateral lobe in 70 (23.3%) patients. The accuracies for detection of any and all positive lymph nodes by tumor location-guided unilateral ePLND were 99.6% and 97.3%, respectively. Among the patients at St. Luke's International Hospital, the accuracies for detection of any and all positive lymph nodes by tumor location-guided unilateral ePLND were estimated to be 99.0% and 97.3%, respectively. CONCLUSIONS: This study proposed tumor location-guided ePLND according to biopsy and MRI findings. This novel strategy is expected to reduce the burden of bilateral ePLND at the cost of acceptable risk of failing to detect positive lymph nodes.

DOI： 10.1245/s10434-024-16294-6

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Language：English   Publisher：Journal of Robotic Surgery  

Our objective was to investigate the long-term functional outcomes of robot-assisted partial nephrectomy (RAPN) combined with three-dimensional (3D) imaging. The 3D images, reconstructed using computed tomography, were introduced in RAPN procedures. The demographic, oncological, functional, and volumetric outcomes of 296 patients who underwent RAPN with and without 3D imaging between 2013 and 2021 were analyzed retrospectively. Propensity score matching (1:1) was performed to adjust for potential baseline confounders. After matching, 71 patients were allocated to each group. In the 3D RAPN (3DRPN) group, functional outcomes significantly improved: the number of patients with over 90% estimated glomerular filtration rate (eGFR) preservation rate (40 vs. 43, P = 0.044), eGFR preservation rate (88.0% vs. 91.6%, P = 0.006), the number of patients with chronic kidney disease (CKD) upstaging (26 vs. 13, P = 0.023), and split renal function preservation rate (operated kidney: 84.9% vs. 88.5%, P = 0.015). The 3DRPN group showed superiority in terms of >90% eGFR preservation (P = 0.010), CKD upstaging-free survival rates (P < 0.001), and volumetric outcomes (excess parenchymal volume: 27.9 vs. 17.7 mL, P = 0.030; parenchyma volume preservation rate: 81.6% vs. 88.8%, P = 0.006). Three-dimensional imaging was positively associated with eGFR preservation (P = 0.023, odds ratio: 2.34) and prevention of CKD upstaging (P = 0.013, odds ratio: 2.90). In this study, RAPN combined with 3D imaging underscored the preservation of eGFR > 90% and the prevention of CKD upstaging by improving the preservation rate of renal parenchyma and split renal function.

DOI： 10.1007/s11701-024-02070-x

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Language：English   Publisher：International Journal of Clinical Oncology  

In the last decade, the standard treatment for advanced renal cell carcinoma (RCC) has evolved, mainly driven by the development and approval of immune checkpoint inhibitors (ICIs). Currently, ICI monotherapy and ICI-based combinations with tyrosine kinase inhibitors and targeted therapies against mammalian target of rapamycin or vascular endothelial growth factor have become new standard treatments for first-line and subsequent-line therapies. ICIs play an important role as an adjuvant postoperative therapy, and this field is the subject of active research. Furthermore, ongoing randomized controlled trials are investigating the clinical value of more intense treatments by combining multiple effective treatments for RCC. Additionally, novel biomarkers for prognosis have been investigated. This study reviews the current evidence on immunotherapy as a treatment for RCC patients, randomized controlled trials, and ongoing studies including RCC patients and recent findings, and discusses future perspectives.

DOI： 10.1007/s10147-023-02446-3

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DOI： 10.1103/PhysRevLett.133.012501

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PubMed

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

根治的前立腺摘除術(RP)後に行う前立腺特異抗原(PSA)モニタリングの4つのモデルの妥当性を検証し、生化学的再発(BCR)検出を改善する修正モデルを検討した。2009～2022年にロボット支援RPを受けた患者の臨床病理学的データを調べ、4つのモデルで仮想上経過観察時のPSA値を推定した。BCR検出に最適なPSA値は0.2～0.4ng/mLと定義した。患者896例(年齢中央値66歳)を解析した。追跡期間中央値21.4ヵ月の間に128例(14.3%)がBCRを認めた。BCRが検出されたPSA値0.4ng/mL超の患者は、慶應モデル、修正慶應モデル、国立がん研究センター中央病院(NCCH)モデル、および米国泌尿器科学会(AUA)/米国放射線腫瘍学会(ASTRO)モデルでそれぞれ14例(10.9%)、3例(2.3%)、12例(9.4%)、および11例(8.6%)であった。殆どの患者は、術後1年目にPSA値0.4ng/mL超でBCRが検出された。術後6ヵ月以内の間隔に変更すると、術後1年以内のPSA>0.4ng/mLのBCR検出は上記のモデルそれぞれで8/9例(88.9%)、1/2例(50.0%)、5/6(83.3%)、4/4例(100%)で回避された。以上より、RP後のBCR検出のためのPSAモニタリングを最適にするための修正案が示唆された。

Language：English   Publisher：International Journal of Urology  

Background: Early detection of biochemical recurrence (BCR) after radical prostatectomy (RP) is crucial for early treatment and improving survival outcomes. The optimal prostate-specific antigen (PSA) monitoring remains unclear, and several models have been proposed. We aimed to externally validate four models for optimal PSA monitoring after RP and propose modifications to improve them. Methods: We reviewed the clinicopathological data of 896 patients who underwent robot-assisted RP between 2009 and 2022. We examined all PSA values and estimated the PSA value for four monitoring schedules at each time point in the virtual follow-up. We defined the ideal PSA for BCR detection between 0.2 and 0.4 ng/mL. Results: During the median follow-up of 21.4 months, 128 (14.3%) patients presented BCR. The original and modified Keio models, National Cancer Center Hospital model, and American Urological Association/American Society for Radiation Oncology model detected BCR in 14 (10.9%), three (2.3%), 12 (9.4%), and 11 (8.6%) patients with PSA >0.4 ng/mL. Most patients experienced BCR detected with PSA >0.4 ng/mL during the first year postoperative. The modification of interval within 6 months postoperative avoided BCR detection with PSA >0.4 ng/mL within the first year postoperative in 8/9 (88.9%), 1/2 (50.0%), 5/6 (83.3%), and 4/4 (100%) for the original and modified Keio models, National Cancer Center Hospital model, and American Urological Association/American Society for Radiation Oncology model, respectively. Conclusion: We validated four models for PSA monitoring after RP to detect BCR and suggested modifications to avoid detections out of the desired range of PSA. These modifications could help to establish an optimal PSA monitoring schedule after RP.

DOI： 10.1111/iju.15379

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Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

前立腺癌に対する炭素イオン線治療(CIRT)後のサルベージロボット支援前立腺全摘術(RARP)の手術アウトカムと腫瘍アウトカムについて検討した。2020～2023年に、CIRT後に局所再発をきたしてRARPを施行された前立腺癌患者10例(中央値69歳)を対象とした。拡大骨盤リンパ節郭清(PLND)によるサルベージRARPを行い、臨床病理学的特徴、周術期アウトカムおよび術後アウトカムを評価した。CIRT後の局所再発時のPSA中央値は4.02ng/mL、生検によるGleason分類ではグレードIIが1例、グレードIIIが2例、グレードIVが2例、グレードVが5例であり、術前の臨床的Tステージは9例がT2、1例のみT3a、初期診断から局所再発までは中央値58.5ヵ月であった。RARPに際して全例にPLND、1例に両側神経温存手術を行い、手術時間中央値は235分、コンソール時間中央値は171分、推定出血量中央値は150mLであった。直腸損傷といった周術期合併症や術後90日以内の再入院、尿道狭窄は認められなかった。腫瘍アウトカムに関して、1例が術後31.2ヵ月に生化学的再発を呈した。CIRT後に局所再発をきたした前立腺癌患者に対して、RARPは実行可能な手技であることが示された。

Language：English   Publisher：Asian Journal of Endoscopic Surgery  

Purpose: This study presents the surgical and oncological outcomes of salvage robot-assisted radical prostatectomy (RARP) after carbon ion radiotherapy at a single institution. Methods: Patients who underwent salvage RARP for local recurrence after carbon ion radiotherapy at Kyushu University Hospital between 2020 and 2023 were included. A single surgeon performed salvage RARP with extended pelvic lymph node dissection. Clinicopathological characteristics and perioperative and postoperative outcomes were prospectively collected and electronically recorded. Results: Ten cases were included. The preoperative clinical T-stage was T2, except for one case with T3a. The median console time was 171 min (range, 135–226 min). No severe perioperative or postoperative complications were noted. The pathological T-stage was T2, T3a, and T3b in four, four, and two cases, respectively. Biochemical recurrence was observed in one patient at 31.2 months after surgery. For patients with more than 1 year of follow-up, urinary continence recovery with ≤1 pad was achieved in two cases within 1 year, whereas four cases did not recover urinary continence within 1 year. Conclusions: This case series demonstrated the feasibility of salvage RARP after carbon ion radiotherapy. Although the urinary continence recovery was modest, short-term disease control was favorable.

DOI： 10.1111/ases.13279

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Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：Journal of Robotic Surgery  

The novel technique of lateral pelvic fascia preservation (LPFP) in robot-assisted radical prostatectomy (RARP) has been reported to improve urinary continence recovery. We aimed to investigate surgical and oncological outcomes after RARP using the LPFP technique and compare them with conventional RARP. This study included patients who underwent RARP with and without the LPFP technique. Time to urinary continence recovery was compared between the LPFP and non-LPFP groups using univariate, multivariate, and propensity-score matched analysis. Perioperative and postoperative outcomes were compared between the two groups using univariate analysis. We included 139 patients who underwent RARP, 68 in the LPFP group and 71 in the non-LPFP group. The LPFP technique was associated with a shorter time to urinary continence recovery, a shorter operative time and lower estimated blood loss. Surgical and oncological outcomes, including complications, pathological T-stage, surgical margin status, and biochemical recurrence-free survival, were comparable between the two groups. This study demonstrated that the LPFP technique improves urinary continence recovery and operative times without compromising surgical and oncological outcomes. The use of this technique in patients with clinically localized prostate cancer is recommended.

DOI： 10.1007/s11701-023-01702-y

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DOI： 10.1016/j.annonc.2023.09.052

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Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：Anticancer Research  

Background/Aim: Testosterone is essential for prostate cancer development and growth. This study aimed to investigate the relationship between testosterone in seminal vesicles and prostate cancer incidence and its malignant phenotype. Patients and Methods: After obtaining institutional review board approval, seminal vesicle fluid samples were collected from patients who underwent prostatectomy or cystectomy. Pathological review demonstrated that 26 patients had benign prostate tissue and 149 had prostate cancer. First, testosterone levels in seminal vesicle fluid from benign prostate and prostate cancer samples were compared. Next, the relationship between pathological stage, International Society of Urological Pathology (ISUP) score, and testosterone concentrations in seminal vesicle fluid in the prostate cancer group were examined. Results: Testosterone in seminal vesicles was significantly higher in the prostate cancer group [median (range), 1.94 (0.17-4.32) ng/ml] than in the benign prostate group (mainly bladder cancer) [1.45 (0.60-2.78) ng/ml] (p=0.001). Testosterone in seminal vesicles showed no difference in relation to pathological stage (pT2 vs. pT3) or ISUP score (12 vs. 345) (p=0.480 and p=0.964, respectively). Neoadjuvant chemotherapy for other cancers (e.g., bladder or rectal cancer) significantly reduced testosterone in seminal vesicles (p=0.013). Multivariate regression analysis revealed that testosterone in seminal vesicles was significantly correlated with prostate cancer, and not with neoadjuvant chemotherapy (p=0.023, p=0.457, respectively). Conclusion: Testosterone in seminal vesicles may contribute to prostate cancer incidence, but has no relationship with pathological grading.

DOI： 10.21873/anticanres.16618

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Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：International Journal of Urology  

Objective: The precise diagnosis of prostate cancer (PC) is crucial to avoid underdiagnosis, overdiagnosis, and overtreatment. We aimed to compare clinically significant PC (csPC) detection between MRI/ultrasound fusion-targeted prostate (TBx) compared to systematic biopsy (SBx) in biopsy-naïve Japanese men. Methods: We included patients with suspect PC due to elevated PSA level or abnormal digital rectal examination, or both. csPC was defined as International Society Urological Pathology (ISUP) grade group ≥2 (csPC-A) and ISUP grade group ≥3 (csPC-B). Results: This study included 143 patients. Overall PC detection was 66.4% for SBx and 67.8% for MRI-TBx. MRI-TBx presented a significantly higher rate of csPC detection (csPC-A 67.1% vs. 58.7%, p = 0.04, and csPC-B 49.6% vs. 39.9%, p < 0.001) and significantly lower detection of non-csPC-A (0.6% vs. 6.7%). Importantly, MRI-TBx missed 4.9% (7/143) of csPC-A and only 0.7% (1/143) of csPC-B. On the other hand, SBx alone missed 13.3% (19/143) of csPC-A and 4.2% (6/143) of csPC-B. Conclusion: MRI-TBx significantly outperformed 12-cores SBx for csPC detection and decreased non-csPC detection in biopsy-naive men. Performing MRI-TBx without SBx would have missed some csPC, supporting that MRI-TBx synergizes with SBx to increase csPC detection.

DOI： 10.1111/iju.15188

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Language：English   Publisher：John Wiley & Sons Australia, Ltd  

前立腺癌(PC)が疑われる生検歴のない日本人男性において、MRI-超音波融合標的前立腺生検(TBx)と系統生検(SBx)を用いて、臨床的に重大なPC(csPC)の検出率を比較した。2020～2022年に日本の単一施設でPC疑いのためにMRI-TBx+SBxを行った143例(中央値70歳)を対象とするコホート研究を行った。csPCの定義は、国際泌尿器病理学会(ISUP)グレード群2以上(csPC-A)およびISUPグレード群3以上(csPC-B)とした。全PC検出率は、SBxで66.4%、MRI-TBxで67.8%であった。MRI-TBxはSBxに比べてcsPC検出率が有意に高く(csPC-Aは67.1 vs 58.7%、csPC-Bは49.6 vs 39.9%)、非csPC-A検出率が有意に低かった(0.6 vs 6.7%)。MRI-TBxの見逃し率はcsPC-Aは4.9%(7/143例)、csPC-Bは0.7%(1/143例)であったが、SBxではそれぞれ13.3%(19/143例)、4.2%(6/143例)であった。

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：International Journal of Urology  

Objectives: To investigate the impact of extended pelvic lymph node dissection (ePLND) on urinary incontinence (UI) at early post-surgery robot-assisted radical prostatectomy (RARP). Methods: Patients who underwent RARP without cavernous nerve sparing were included between 2014 and 2019. Patient data were obtained prospectively. The associations between ePLND and postoperative urinary continence were defined as a maximum of one daily pad use. International prostate symptom score (IPSS) was examined. Expression of synaptophysin and tyrosine hydroxylase (TH) in perilymph node adipose tissue (PLA) was evaluated by immunohistochemistry. Results: In total, 186 and 163 patients underwent RARP with and without ePLND. Urinary continence rate at 1 month postoperatively among patients with ePLND was lower than those without ePLND (24.1% vs. 35.1%, p < 0.05), however, not significantly different at 3, 6, and 12 months after RARP (57.4 vs. 62.6%, 73.1 vs. 74.2%, and 83.0 vs. 81.2%, respectively). Total and voiding plus postvoiding IPSS scores at 1 month were higher in patients with ePLND than in those without ePLND (14.5 ± 0.5 vs. 13.6 ± 0.6, 7.0 ± 0.3 vs. 6.2 ± 0.4, respectively, p < 0.05). In univariate and multivariate analyses, larger prostate volume and ePLND were factors associated with an increased UI rate. Among patients who underwent ePLND, synaptophysin and TH-positive nerve fibers were detected in PLA. Conclusions: Detection of synaptophysin and TH-immunopositive nerves suggested denervation of sympathetic and peripheral nerves caused by ePLND might be associated with a higher UI rate and poor urinary symptoms at an early stage after RARP.

DOI： 10.1111/iju.15119

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Language：English   Publisher：John Wiley & Sons Australia, Ltd  

ロボット支援根治的前立腺摘出術(RARP)後早期において拡大骨盤リンパ節郭清(ePLND)が尿失禁(UI)に及ぼす影響について検討した。海綿体神経温存を行わずにRARPを行った349例をePLND施行群186例(中央値66.5歳)とePLND非施行群163例(中央値68歳)に分類した。術後早期における排尿調節率のほか、国際前立腺症状スコア(IPSS)、リンパ節周囲脂肪組織(PLA)中のシナプトフィジンとチロシンヒドロラーゼ(TH)発現を評価した。ePLND施行群、非施行群とも術前にUIの発症はなく、術後1ヵ月における排尿調節率はePLND群が24.1%、非ePLND群が35.1%であり、ePLND群の方が有意に低かった。3、6、12ヵ月後の排尿調節率に有意な群間差はみられなかった。IPSS総スコアは1ヵ月後においてePLND群の方が有意に高く、3、6、12ヵ月後に有意差はなく、IPSS蓄尿スコアはいずれの時点でも有意な群間差はなく、IPSS排尿・排尿後症状スコアは1ヵ月後においてePLND群の方が有意に高値を示していた。多変量ロジスティック回帰分析では、前立腺容積とePLNDの施行がUI発症の独立予測因子として抽出された。ePLND群ではPLAにおいてシナプトフィジンとTH陽性神経線維が検出され、ePLNDの施行による脱神経がUI発症と関連することが示唆された。

Language：Japanese   Publisher：日本腎泌尿器疾患予防医学研究会  

過去9ヵ月間に前立腺癌に対してSpaceOARを用いてハイドロゲルスペーサーを留置した19例(56～85歳、中央値73歳)を対象に、ハイドロゲルスペーサー留置後30日以内の合併症について検討した。その結果、合併症は2例で、1例はハイドロゲルが直腸内へ迷入、1例は前立腺被膜へ迷入した。いずれも導入初期に起きており、生理食塩水で前立腺直腸間のスペースが十分に拡がることを確認した。針先を動かさずハイドロゲルを注入することが重要である。

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Language：English   Publishing type：Research paper (scientific journal)  

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Language：English   Publisher：Molecular Cancer Therapeutics  

Although adoptive transfer of T cells genetically engineered to express chimeric antigen receptor (CAR) or T-cell receptor (TCR) has been actively developed and applied into clinic recently, further improvement of these modalities is highly demanded, especially in terms of its efficacy. Because we previously revealed the profound enhancement of antitumor effects of CAR T cells by concomitant expression of IL7 and CCL19, this study further explored a potential of IL7/CCL19 production technology to augment antitumor effects of TCR T cells. IL7/CCL19-producing P1A tumor antigen-specific TCR T cells (7 × 19 P1A T cells) demonstrated significantly improved antitumor effects, compared with those without IL7/ CCL19 production, and generated long-term memory responses. The antitumor effects of 7×19 P1A T cells were further upregulated by combination with anti–PD-1 antibody, in which blockade of PD-1 signal in both 7×19 P1A T cells and endogenous T cells plays an important role. Taken together, our study demonstrated that concomitant production of IL7 and CCL19 by genetically engineered tumor-reactive T cells could synergize with PD-1 blockade therapy to generate potent and long-lasting antitumor immunity.

DOI： 10.1158/1535-7163.MCT-21-0400

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Event date： 2022.6

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