Risk factors for the long-term persistent genitourinary toxicity after stereotactic body radiation therapy for localized prostate cancer: A single-center, retrospective study of 306 patients.

OBJECTIVES: To identify risk factors for the long-term persistent genitourinary toxicity (GUT) after stereotactic body radiation therapy (SBRT) for localized prostate cancer (PCa). METHODS: A total of 306 patients who underwent SBRT at our institution between March 2017 and April 2022 were retrospectively evaluated. SBRT was performed at 35 Gy in five fractions over 5 or 10 days. Factors related to the long-term persistence of acute GUT after SBRT were analyzed. RESULTS: During the median follow-up period of 39.1 months, 203 (66%) patients experienced any grade of acute GUT, which remained in 78 (26%) patients 6 months after SBRT. Multivariate analysis revealed that age ≥75 years was consistently a significant independent risk factor for any grade of acute GUT 6, 12, and 24 months after SBRT (hazard ratio [HR] 2.31, p = 0.010; HR 2.84, p = 0001; and HR 3.05, p = 0.009, respectively). Older age was not a significant risk factor for the development of grade ≥2 acute GUT. The duration of acute GUT was significantly longer in the older group than in the nonolder group (median duration = 234 vs. 61 days, p < 0.001), and the incidence of persistent GUT was significantly more frequent in the older group beyond 6 months after SBRT. CONCLUSIONS: Older age is a significant independent risk factor for the long-term persistent GUT after SBRT for localized PCa.

Retzius-sparing robotic prostatectomy is associated with higher positive surgical margin rate in anterior tumors, but not in posterior tumors, compared to conventional anterior robotic prostatectomy.

Objectives: The analysis of the oncological outcomes and postoperative continence recovery between conventional robotic-assisted radical prostatectomy (cRARP) and Retzius-sparing RARP (rsRARP), and the effect of the tumor location on them. Materials and methods: A total of 317 patients who underwent cRARP (n = 228) or rsRARP (n = 89) from August 2017 to July 2020 were assessed. Patients were categorized into groups based on the tumor location by pathology. Positive surgical margin (PSM) rates and biochemical recurrence (BCR)-free survivals and continence recovery were compared between the two procedures. Results: Patient age, prostate-specific antigen (PSA) levels, clinical stages, and Gleason score were not significantly different between the two groups. There was no significant difference in PSM rates (25.8% vs. 33.7%, p = 0.13) or BCR-free survivals (p = 0.28) between cRARP and rsRARP in patients. When tumor was located in the anterior lesion in the prostatectomy pathology, rsRARP was associated with significantly higher PSM rates than cRARP (53.3% in rsRARP vs. 27.0% in cRARP, p = 0.0086), while BCR-free survival did not vary significantly (hazard ratio: 2.15, p = 0.11). When tumors were identified in the posterior in prostatectomy pathology, PSM rates (28.8% in rsRARP vs. 24.7% in cRARP, p = 0.59) or BCR-free survivals (hazard ratio: 0.78, p = 0.51) did not differ significantly between the two groups. rsRARP yielded superior continence recovery in all time points compared to cRARP, which was not affected by the pathological tumor location. Conclusion: In posterior tumors, rsRARP results in similar oncological outcomes as cRARP with superior continence recovery, while in anterior tumors, rsRARP may associate with higher PSM rate, combined with improved continence recovery.

Combination of biparametric magnetic resonance imaging with prostate-specific antigen density to stratify the risk of significant prostate cancer: Initial biopsy and long-term follow-up results.

OBJECTIVES: To assess whether the combination of biparametric magnetic resonance imaging with prostate-specific antigen density can properly stratify the risk of significant prostate cancer in patients undergoing prostate biopsies and how this approach affects the detection of prostate cancer during follow-up in patients who do not undergo prostate biopsy. METHODS: In total, 411 biopsy-naïve patients who had elevated prostate-specific antigen levels and then underwent biparametric magnetic resonance imaging for suspicious prostate cancer were analyzed: 203 patients underwent prostate biopsies, whereas 208 patients did not. Significant prostate cancer detection rates stratified by the combination of Prostate Imaging Reporting and Data System score and prostate-specific antigen density were assessed in patients who underwent prostate biopsies. The cumulative incidence of prostate cancer detection during the follow-up was assessed in patients who omitted biopsy. RESULTS: The negative predictive value for significant prostate cancer was 89% for Prostate Imaging Reporting and Data System scores 1-3, which increased to 97% when prostate-specific antigen density <0.15 ng/ml/cm3 was combined. Among patients who did not undergo biopsy, patients with Prostate Imaging Reporting and Data System scores 1-3 plus prostate-specific antigen density <0.15 ng/ml/cm3 included significantly less cases in which significant prostate cancer was detected during the follow-up, compared with the others (3.2% versus 17% at 36 months). CONCLUSIONS: Restriction of prostate biopsies to patients with Prostate Imaging Reporting and Data System scores 4-5 or prostate-specific antigen density ≥0.15 ng/ml/cm3 proved to be the good biopsy strategy, effectively balancing risks and benefits.

Hypereosinophilia is a predictive biomarker of immune checkpoint inhibitor-induced hypopituitarism in patients with renal cell carcinoma.

BACKGROUND: This study aimed to evaluate whether hypereosinophilia is a clinical biomarker of immune checkpoint inhibitor-induced hypopituitarism in patients with renal cell carcinoma treated with nivolumab plus ipilimumab. METHODS: This was a retrospective cohort study conducted at Jichi Medical University Saitama Medical Center between January 2018 and December 2020. In total, 12 patients with renal cell carcinoma who presented with immune checkpoint inhibitor-induced hypopituitarism were enrolled in this study. The clinical parameters and symptoms at baseline, last visit, and onset of hypopituitarism were analyzed. RESULTS: The median period from the initial treatment with immune checkpoint inhibitors to the onset of hypopituitarism was 82.5 (range: 56-196) days. Most patients developed hypopituitarism within 6 months. One patient presented with hypophysitis and 11 patients presented with isolated adrenocorticotropic hormone deficiency. The major symptoms noted at onset were fatigue (66.7%) and loss of appetite (41.7%). None of the patients had symptoms during the last visit. However, four developed hypereosinophilia. Eosinophil fraction (%) and eosinophil count (/µL) increased during the last visit and at the onset of hypopituitarism, respectively. The serum sodium and plasma glucose levels were similar. CONCLUSIONS: The eosinophil count increased before the onset of hypopituitarism. Thus, hypereosinophilia can be an early predictor of hypopituitarism.

[A Case of Metachronous Occurrence of Interstitial Pneumonitis and Hypophysitis Following Nivolumab Plus Ipilimumab for Metastatic Renal Cell Carcinoma].

A 71-year-old man presented with neck pain. He was diagnosed with renal cell carcinoma of the left kidney with lung and bone metastases. After laparoscopic left nephrectomy, nivolumab plus ipilimumab was introduced as a first-line therapy for intermediate risk metastatic renal cell carcinoma based on the IMDC risk classification. After four cycles of nivolumab plus ipilimumab, he experienced dyspnea and was diagnosed with interstitial pneumonitis. Corticosteroid therapy was initiated, after which the symptoms of interstitial pneumonitis subsided. Corticosteroid therapy was tapered and discontinued after two months of treatment. The patient experienced fatigue at one week after the discontinuation of corticosteroid therapy and was diagnosed with isolated ACTH deficiency due to hypophysitis. He recovered after hydrocortisone treatment. This case involved two different immune-related adverse events (irAE), interstitial pneumonitis and hypophysitis, that occurred asynchronously following nivolumab plus ipilimumab therapy. It is important to observe the patient's condition carefully whether additional irAEs arise when corticosteroid therapy is tapered or discontinued.

Risks and complications of robot-assisted radical prostatectomy (RARP) in patients receiving antiplatelet and/or anticoagulant therapy: a retrospective cohort study in a single institute.

The objective of the study was to evaluate the risk of bleeding complications in patients undergoing robot-assisted radical prostatectomy (RARP) while taking antiplatelet (AP) and/or anticoagulant (AC) agents. We analyzed the data of 334 patients undergoing RARP from May 2015 to May 2019. Patients were categorized into AP, AC, and control groups; the bleeding complications were compared among them. The end points were the estimated blood loss, decrease in hemoglobin level, and bleeding complications. The patient characteristics did not differ significantly among groups, with the exception of ASA scores, which were significantly higher in the AP and AC groups vs. the control group. The estimated blood loss and hemoglobin decrease were not significantly different between the AP and AC groups and the control group. The frequency of bleeding complications did not differ significantly between the AP and the control groups, but was significantly higher in the AC vs. the control group (4.3% in the AP and 23.5% in the AC group vs. 3.7% in the control group; P = 0.63 and P < 0.01, respectively). There was no significant difference in bleeding complications between the AP continuation (continuation of a single AP) and the AP interruption group or between the heparin bridging and the AC interruption group. All bleeding complications observed in the AC group occurred after resuming AC therapy. RARP can be performed safely with continuation of a single AP, and in patients taking ACs by interrupting these agents or via heparin bridging, without increasing intraoperative bleeding, whereas postoperative bleeding complications may increase after resuming ACs.

Dose-volume Histogram-based Predictors for Hematuria and Rectal Hemorrhage in Patients Receiving Radiotherapy After Radical Prostatectomy.

AIM: The aim of this study was to evaluate the dose-volume histogram parameters for late hematuria and rectal hemorrhage in patients receiving radiotherapy after radical prostatectomy. PATIENTS AND METHODS: Data of 86 patients treated between January 2006 and June 2019 were retrospectively evaluated. The median radiation dose was 64 Gy in 32 fractions. Receiver operating characteristic (ROC) curves were used to identify optimal cut-off values for late adverse events. RESULTS: Eleven patients experienced hematuria, and the 5-year cumulative rate was 18%. Four patients experienced rectal hemorrhage, and the 5-year cumulative rate was 7%. ROC curve analysis demonstrated the following significant cut-off values: bladder V50 Gy: 43% (p=0.02) and V40 Gy: 50% (p=0.03) for hematuria, and rectum V60 Gy: 13% (p=0.04) and V50 Gy: 33% (p=0.03) for rectal hemorrhage. CONCLUSION: This is the first study to identify dose constraints that may reduce hematuria and rectal hemorrhage in patients receiving radiotherapy in the postoperative setting.

A Novel Biomarker for Acute Kidney Injury, Vanin-1, for Obstructive Nephropathy: A Prospective Cohort Pilot Study.

Background: Vanin-1 is a novel acute kidney injury (AKI) biomarker that has not been clinically investigated as a biomarker for obstructive nephropathy. This study investigated the diagnostic value of vanin-1 as a biomarker for adult obstructive nephropathy by comparing it to existing AKI biomarkers. Methods: A total of 49 patients, 21 controls, and 28 hydronephrosis (HN) cases were assessed. AKI biomarkers in bladder (BL) urine and renal pelvic (RP) urine in the HN group were compared to each BL marker in the control group. In a subgroup of cases receiving interventions for obstructive nephropathy, the BL values of each biomarker were assessed after the intervention. Results: RP vanin-1 levels were significantly higher while BL vanin-1 levels were marginally higher in the HN group than in the control group. The area under the receiver operating characteristics curve values for RP and BL vanin-1 were 0.9778 and 0.6386, respectively. In multivariate analyses, BL vanin-1 and N-acetyl-ß-D-glucosaminidase (NAG), but not kidney injury molecule-1 (KIM-1) or neutrophil gelatinase-associated lipocalin (NGAL), were independent factors for predicting the presence of HN. In cases receiving interventions, vanin-1 decreased significantly from 1 week after the intervention in cases of moderate to severe obstructive nephropathy compared to RP values at baseline. Conclusion: Urinary vanin-1 is a useful biomarker to detect and monitor the clinical course of obstructive nephropathy.

Tumor lysis syndrome following cabazitaxel administration for metastatic castration-resistant prostate cancer: A case report.

INTRODUCTION: Tumor lysis syndrome is a rare and potentially fatal complication of oncological treatment. It is characterized by biochemical changes associated with the rapid lysis of malignant cells, usually after chemotherapy. Tumor lysis syndrome is typically noted in patients with hematological malignancies, and it rarely occurs in patients with solid tumors. CASE PRESENTATION: We report a case of tumor lysis syndrome after cabazitaxel administration for metastatic castration-resistant prostate cancer. To our knowledge, tumor lysis syndrome after cabazitaxel therapy has not been reported previously. The patient was a 77-year-old man who developed clinical tumor lysis syndrome after a single dose of cabazitaxel for metastatic castration-resistant prostate cancer. He was treated with hydration and the recombinant uricolytic agent rasburicase, and his condition improved. CONCLUSION: It is extremely important to assess the risk factors for tumor lysis syndrome and to perform active prevention procedures in order to avoid fatal outcomes. It may be beneficial to use rasburicase in patients with established tumor lysis syndrome.

Risks and complications of transurethral resection of bladder tumors in patients receiving antiplatelet and/or anticoagulant therapy: a retrospective cohort study.

BACKGROUND: Information on the safety of transurethral resection of bladder tumors (TURBT) in patients receiving anti-thromboembolic drugs is currently lacking. This study aimed to evaluate the clinical safety of TURBT in patients receiving anti-thromboembolic agents compared with patients not taking these agents and patients who interrupted their use perioperatively. METHODS: We retrospectively analyzed data for patients who underwent TURBT at Jichi Medical University Saitama Medical Center from September 2013 to August 2016.Patients who underwent surgery while receiving antiplatelet and/or anticoagulant drugs were allocated to the continuation group, those who interrupted these drugs comprised the interruption group, and those who did not use these agents were designated as the control group. We compared the patient characteristics, hemoglobin levels, and complications among the three groups. RESULTS: A total of 174 patients were analyzed including 19, 18, and 137 in the continuation, interruption, and control groups, respectively. There were no significant differences in patient and tumor characteristics, apart from age, among the three groups. Decreases in hemoglobin levels were similar in the continuation, interruption, and control groups (-0.50 g/dl, -0.40 g/dl, and -0.50 g/dl, respectively).Significantly more patients in the continuation group experienced clot retention compared with the control group (21% vs 5%, p = 0.03). Large tumor size tended to be a risk factor for clot retention in the continuation group (p = 0.07). No patient in the continuation or interruption group required blood transfusion, compared with two patients (1%) in the control group. No patients in any of the groups experienced cardiovascular events during their hospital stay or required rehospitalization for hematuria after discharge. CONCLUSIONS: TURBT can be performed safely in patients who continue to take antiplatelet and/or anticoagulant agents, without increasing the risks of severe hemorrhage and blood transfusion. However, the risk of postoperative clot retention may be increased in these patients.

Two cases of somatic-type malignancy as a very late relapse of testicular cancer successfully managed by surgical resection.

A late-relapse germ cell tumor might contain malignant non-germ cell tumors, known as 'somatic-type malignancy (SM)'. The development of a secondary SM is rare, and this phenomenon remains poorly understood. Case 1 developed lung metastasis 13 years after chemotherapy followed by retroperitoneal lymph node dissection for stage IIA non-seminoma. The tumor increased in size after chemotherapy. The patient underwent a pneumonectomy. Pathology revealed an adenocarcinoma with immature teratoma. The patient has experienced no relapse for 9 years. Case 2 developed a pelvic tumor after 10 years of surveillance for stage I seminoma. The tumor increased in size after chemotherapy. The patient underwent pelvic tumor resection with cystectomy. Pathology revealed a mature teratoma with SMs consisting of sarcoma and adenocarcinoma. The patient has experienced no relapse for 6 months. Surgical resection played a major role in the treatment of very late-relapse germ cell tumors with SM.

Transperineal ultrasound-guided prostate biopsy is safe even when patients are on combination antiplatelet and/or anticoagulation therapy.

BACKGROUND: To assess whether hemorrhagic complications associated with transperineal prostate biopsy increased in patients on antiplatelet and/or anticoagulant therapy. METHODS: In total, 598 consecutive patients underwent transperineal prostate biopsy. The medication group comprised patients who took anti-thromboembolic agents, and the control group comprised those who did not take these agents. No anti-thromboembolic agent was stopped before, during, or after prostate biopsy in the medication group. Complications developing in both groups were compared and classified using the modified Clavien classification system. Subgroup analyses to compare complications in patients taking single antiplatelet, single anticoagulant, and dual antiplatelet and/or anticoagulant agents, and multivariate analyses to predict bleeding risk were also performed. RESULTS: Of the 598 eligible patients, 149 comprised the medication group and 449 comprised the control group. Hematuria (Grade I) developed in 88 (59.1%) and 236 (52.5%) patients in the medication and control group, respectively (p = 0.18). Clot retention (Grade I) was more frequently observed in the medication group than the controls (2.0% versus 0.2%, respectively, p < 0.05). Hospitalization was more frequently prolonged in the medication than the control group (4.0% versus 0.4% of patients, respectively). No complication of Grade III or higher developed in either group. Hematuria was more frequent in patients taking a single anticoagulant (p = 0.007) or two anti-thromboembolic agents (p = 0.04) compared with those taking a single antiplatelet agent. Other complications were generally similar among the groups. In the multivariate analysis, taking more than two anti-thromboembolic agents was the only significant risk factor for bleeding events. CONCLUSION: No severe complication developed after the transperineal biopsies in either group, although minor bleeding was somewhat more frequent in the medication group. It may not be necessary to discontinue anticoagulant and/or antiplatelet agents when transperineal prostate biopsy is contemplated.

Combination of prostate imaging reporting and data system (PI-RADS) score and prostate-specific antigen (PSA) density predicts biopsy outcome in prostate biopsy naïve patients.

OBJECTIVE: To assess the value of the Prostate Imaging Reporting and Data System (PI-RADS) scoring system, for prostate multi-parametric magnetic resonance imaging (mpMRI) to detect prostate cancer, and classical parameters, such as prostate-specific antigen (PSA) level, prostate volume and PSA density, for predicting biopsy outcome in biopsy naïve patients who have suspected prostate cancer. PATIENTS AND METHODS: Patients who underwent mpMRI at our hospital, and who had their first prostate biopsy between July 2010 and April 2014, were analysed retrospectively. The prostate biopsies were taken transperineally under transrectal ultrasonography guidance. In all, 14 cores were biopsied as a systematic biopsy in all patients. Two cognitive fusion-targeted biopsy cores were added for each lesion in patients who had suspicious or equivocal lesions on mpMRI. The PI-RADS scoring system version 2.0 (PI-RADS v2) was used to describe the MRI findings. Univariate and multivariate analyses were performed to determine significant predictors of prostate cancer and clinically significant prostate cancer. RESULTS: In all, 288 patients were analysed. The median patient age, PSA level, prostate volume and PSA density were 69 years, 7.5 ng/mL, 28.7 mL, and 0.26 ng/mL/mL, respectively. The biopsy results were benign, clinically insignificant, and clinically significant prostate cancer in 129 (45%), 18 (6%) and 141 (49%) patients, respectively. The multivariate analysis revealed that PI-RADS v2 score and PSA density were independent predictors for prostate cancer and clinically significant prostate cancer. When PI-RADS v2 score and PSA density were combined, a PI-RADS v2 score of ≥4 and PSA density ≥0.15 ng/mL/mL, or PI-RADS v2 score of 3 and PSA density of ≥0.30 ng/mL/mL, was associated with the highest clinically significant prostate cancer detection rates (76-97%) on the first biopsy. Of the patients in this group with negative biopsy results, 22% were subsequently diagnosed as prostate cancer. In contrast, a PI-RADS v2 score of ≤3 and PSA density of <0.15 ng/mL/mL yielded no clinically significant prostate cancer and no additional detection of prostate cancer on further biopsies. CONCLUSIONS: A combination of PI-RADS v2 score and PSA density can help in the decision-making process before prostate biopsy and in the follow-up strategy in biopsy naïve patients. Patients with a PI-RADS v2 score of ≤3 and PSA density of <0.15 ng/mL/mL may avoid unnecessary biopsies.

[SMALL CELL CARCINOMA OF THE PROSTATE: A CASE REPORT OF RELATIVE LONG-TERM SURVIVAL].

Small cell carcinoma of the prostate (SCCP) is rare, and no standard treatment regimen has yet been established. The overall prognosis remains poor. We experienced a case who obtained relative long-term survival with two types of chemotherapy treatments. A 69-year-old man underwent combined androgen blockade (CAB) with a diagnosis of prostate adenocarcinoma (Gleason score = 5 + 3) that was staged T3bN1M1b (initial PSA = 352 ng/ml). Twenty-five months after hormonal therapy, the level of serum PSA had elapsed remain low, however, FDG-PET/CT revealed high value at the lymph node of para-aortic and pelvic lesion. The levels of serum NSE and Pro-GRP elevated, and a prostate re-biopsy revealed a small cell carcinoma. Therefore, he was treated with 12-cycles of combination chemotherapy consisting of etoposide and carboplatin. Then, disease has progressed, so he was changed to second line chemotherapy with amrubicin. He underwent 12-cycles chemotherapy with amrubicin, but he died of cancer 39 months after the initial treatment of SCCP.