Enzalutamide versus Abiraterone Plus Prednisolone for Nonmetastatic Castration-Resistant Prostate Cancer: A Sub-Analysis from the ENABLE Study for PCa.

Enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) can improve the survival of patients with castration-resistant prostate cancer (CRPC). However, the agent that is more effective against nonmetastatic CRPC remains unclear. To evaluate the agent that can be used as the first-line treatment for CRPC, an investigator-initiated, multicenter, randomized controlled trial (ENABLE Study for PCa) including both metastatic and nonmetastatic CRPC was conducted in Japan. The prostate-specific antigen (PSA) response rate, overall survival, some essential survival endpoints, and safety of patients with nonmetastatic CRPC were also analyzed. In this subanalysis, 15 and 26 patients in the ENZ and ABI arms, respectively, presented with nonmetastatic CRPC. There was no significant difference in terms of the PSA response rate between the ENZ and ABI arms (80% and 64%, respectively; p = 0.3048). The overall survival did not significantly differ between the two arms (HR: 0.68; 95% CI: 0.22-2.14, p = 0.5260). No significant differences were observed in terms of radiographic progression-free survival and cancer-specific survival between the ENZ and ABI arms (HR: 0.81; 95% CI: 0.35-1.84; p = 0.6056 and HR: 0.72; 95% CI: 0.19-2.73; p = 0.6443, respectively). Only four and six patients in the ENZ and ABI arms, respectively, had ≥grade 3 adverse events. ABI and ENZ had similar efficacy and safety profiles in patients with nonmetastatic CRPC.

Recurrence of renal cell carcinoma after simultaneous radical nephrectomy and cadaver renal transplant.

Introduction: Generally, renal transplantation is contraindicated in cancer patients, and a certain follow-up period is required. We report a case of late recurrence of renal cell carcinoma in a patient who underwent simultaneous radical nephrectomy and cadaver renal transplantation due to renal cell carcinoma observed during renal transplantation after 12 years. Case presentation: Incidental renal cell carcinoma was found in a 48-year-old man during kidney transplantation who subsequently underwent simultaneous cadaver kidney transplantation and radical nephrectomy. Twelve years after transplantation, he developed an anterior mediastinal tumor, a lung tumor which was resected and a right adrenal gland mass which was resected along with the right kidney. Currently, he is being treated with tyrosine kinase inhibitors owing to the metastasis in the left adrenal gland. Conclusion: In patients with metastatic carcinoma undergoing renal transplant, the indications for surgical procedures and choice of immunosuppressants should be carefully considered.

Enzalutamide Versus Abiraterone plus Prednisolone Before Chemotherapy for Castration-resistant Prostate Cancer: A Multicenter Randomized Controlled Trial.

Background: Enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) improve survival in castration-resistant prostate cancer (CRPC). However, which agent is better for patients with CRPC remains unclear. Objective: To evaluate whether ENZ or ABI is better as first-line treatment for CRPC. Design setting and participants: An investigator-initiated, multicenter, randomized controlled trial was conducted in Japan. The study enrolled 203 patients with CRPC before chemotherapy between February 20, 2015, and July 31, 2019. Patients were randomly assigned 1:1 to the ENZ or ABI arm. Outcome measurements and statistical analysis: The primary endpoint was time to prostate-specific antigen (PSA) progression. Secondary endpoints included the PSA response rate (≥50% decline from baseline), overall survival, and safety. A log-rank test was used for comparison of survival analyses between arms. Results and limitations: After randomization, 92 patients in each arm were treated and analyzed. Time to PSA progression did not significantly differ between the arms (median 21.2 mo for ENZ and 11.9 mo for ABI; hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.51-1.27; p = 0.1732). There was a significant difference in the PSA response rate between the arms (72% for ENZ and 57% for ABI; p = 0.0425). There was no significant difference in overall survival (median 32.9 mo for ENZA and 35.5 mo for ABI; HR 1.17, 95% CI 0.72-1.88; p = 0.5290). Grade ≥3 adverse events were observed in 11% of patients in the ENZA arm and 21% in the ABI arm (p = 0.1044). Conclusions: ENZ did not show any survival benefit in comparison to ABI, but showed a better PSA response rate with a low rate of severe adverse events in CRPC. Patient summary: Results from our study suggest that use of enzalutamide before abiraterone may have potential clinical benefits for patients with castration-resistant prostate cancer.

[CLINICAL STUDY OF THE PROSTATE CANCERS WITH A SERUM PROSTATE SPECIFIC ANTIGEN LEVEL OF MORE THAN 100 ng/ml AT THE FIRST DIAGNOSIS].

In patients with prostate cancer high serum prostate specific antigen (PSA) at diagnosis was generally regarded as a strong impression of advanced disease with distant metastasis and poor prognosis. (Objective) We reported a retrospective study of prognostic factor and Overall survival (OS) in patients with prostate specific antigen (PSA) level of greater than 100 ng/ml (PSA≥100 ng/ml). (Subjects and methods) Between January 2002 and December 2015, 60 patients were diagnosed prostate cancer with PSA≥100 ng/ml and performed hormonal monotherapy at Kanazawa Medical University hospital. We evaluated initial PSA level, Gleason score, Gleason Grading Group, clinical stage, site of metastasis, PSA nadir level, Time to PSA nadir (TTN), serum Hemoglobin (Hb) level, serum C-Reactive Protein (CRP) level, serum Lactate Dehydrogenase (LDH) level, serum Alkaline Phosphatase (ALP) level, clinical passage and survival time. (Results) The median age of the patients was 73 years old (54-90) and the initial PSA levels ranged from 100 ng/ml to 15,823 ng/ml (median 390).Prognostic factors of overall survival were site of metastasis, Gleason score, Gleason Grading Group, PSA nadir level, TTN, serum CRP level, serum LDH level and serum ALP level at the diagnosis. In multivariate analysis serum LDH level remained an independent predictor of OS.

Ureterosciatic hernia treated with ureteral stent placement.

A 92-year-old female with a history of asthma and chronic heart failure presented with left lumber back pain. Physical examination revealed knocking tenderness at the left costal-vertebral angle. Laboratory test results were within normal limits. Abdominal CT showed a left hydroureteronephrosis and an obstruction in the left distal ureter with herniation into the sciatic foramen. A ureteral stent was inserted into the left ureter and was removed after 2 months. She has not complained of pain or showed symptoms since the removal. Our case suggests that doctors consider the possibility of ureterosciatic hernias when examining older patients complaining of lower back pain.

[Clinical Study on the Efficacy and Continuous Docetaxel Based Chemotherapy Treatment for Castration-Resistant Prostate Cancer].

We report a retrospective study on the efficacy, adverse events and the factors for continuous docetaxel (DOC) therapy for patients with castration-resistant prostate cancer (CRPC). Between April 2007 and April 2015, 37 CRPC patients were treated with DOC therapy at Kanazawa Medical University Hospital. DOC was administered every 3 weeks at 70 mg/m2. Prostatic specific antigen (PSA) level, adverse events, cycles of DOC therapy, survival time and clinical passage were examined. Fifteen patients showed a decrease in PSA level of 50% or more, 9 patients showed less than 50% decrease in PSA level and 13 patients showed no decrease in PSA level. Adverse effect of grade 3 consisted of neutropenia in 29.7% and leukocytopenia in 10.8%. The median number of treatment cycles was 11.7 courses. The patients were divided into two groups ; the first group comprised of 26 patients who received short-term DOC therapy (≤10 cycles) and the second group comprised of 11 patients who received long-term DOC therapy (≥11 cycles). The 1-year survival rate was 59 and 100% for the short-term and long-term groups, respectively. Long-term treatment was related to pretreatment PSA nadir, time to progression of CRPC and serum lactate dehydrogenase level.

THE EFFECT OF RADIATION THERAPY FOR BONE METASTASIS IN URINARY ORGAN CANCER.

(Objective) Bone metastasis symptoms are complications that greatly reduce the quality of life (QOL) of cancer patients. We report a retrospective study on the efficacy of radiation therapy for patients with bone metastasis in urinary organ cancer. (Subjects and methods) Subjects are comprised of 17 patients; total irradiated areas consist of 25 sites. There are 5 patients diagnosed with renal cell carcinoma, 1 patient with bladder cancer and 11 patients with prostatic cancer. All of them have undergone radiation therapy for bone metastasis in urinary organ cancer between April 2007 and March 2014 in the Department of Urology, Kanazawa Medical University. The mean age of the patients was 66.7 years old. We looked at irradiated areas, exposure dose and changes of symptom in all patients. (Results) Irradiated areas are thoracolumbar vertebrae (14 sites), cranial base (2 sites), pubic bone (1 site), ilium bone (2 sites), sacral bone (1 site), rib bone (1 site) and hip joint (1 site). The mean exposure dose of one area is 37.5 Gy (13.5-60). 19 irradiated sites which were previously reported to have sharp pain have gained improvement at 16 sites. These 16 sites have comparatively lesser pain or no pain. 8 cases in acknowledgment of walk difficulty, it was with 7 cases walking alone possibility again. (Conclusion) This study showed that radiation therapy have significant improvement in terms of symptoms and QOL for the patients with bone metastasis in urinary organ cancer.

Seed migration after transperineal interstitial prostate brachytherapy with I-125 free seeds: analysis of its incidence and risk factors.

PURPOSE: The purpose of this study was to evaluate the incidence and predictors of seed migration after transperineal interstitial prostate brachytherapy. MATERIALS AND METHODS: From March 2007 to March 2011, 121 patients with stage T1-T2 prostate cancer underwent transperineal interstitial prostate brachytherapy. Pre-planning was performed 3 weeks prior to implantation, and the implants were inserted using the standard parallel needle insertion technique. All patients underwent a series of radiographs [chest radiography, kidney-ureter-bladder (KUB) radiography, and a CT scan] to assess whether seed migration had occurred on postoperative days 1 and 30, and 12 months. RESULTS: Seed migration occurred in 31 (25.6 %) of 121 patients. A total of 51 of 7,883 (0.65 %) implanted seeds migrated. Migration was detected on postoperative day 1 in 16 patients, day 30 in 13 patients and at 12 months in 4 patients (migration occurred at different times in 2 patients). The migrated seeds were found in the lungs, pelvis, heart, mediastinum, kidney, inguinal canal, liver and sacrum. The number of needles was a statistically significant factor in seed migration. CONCLUSIONS: The seeds migrated to many organs. No decrease in the dose administered to the prostate or adverse effects associated with seed migration were noted.

Renal protective effects of erythropoietin on ischemic reperfusion injury.

While the problem of organ shortage has not yet been solved, the number of patients who need to be treated with dialysis due to end-stage renal disease (ESRD) is increasing each year. With the aim of eliminating dialytic therapy as much as possible, the opportunities for organ donation from expansive criteria donor (ECD) or marginal donors due to cardiac death have been increasing. With the purpose of extracting organs in a state in which the function is preserved as much as possible, we reexamined the conditions of tissue disorders resulting from temporary ischemia of the organs as well as changes in tissue function and the effects on the preservation of renal function over time by using rat models in order to clinically utilize erythropoietin, which has inhibitory effects on ischemia-reperfusion disorder, as has been conventionally reported. With 8- to 9-week-old Wister male rats, after the right kidney had been resected under general anesthesia, the left renal artery was clamped to inhibit the blood flow for 45 min. At 30 min before inhibiting the blood flow and after releasing the inhibited blood flow, 100 U/kg of recombinant human erythropoietin (rhEPO) was administered via the inferior vena cava and the abdominal cavity, and then the tissues and blood samples were extracted at 6 and 24 h after the release. The renal tissue specimens were evaluated using H&E staining and TUNEL staining in order to observe differences in the expression of apoptosis as well as the renal function and changes in the emergence of active oxygen were investigated by using samples that had been obtained from drawn blood. Moreover, we examined the degree of renal dysfunction by means of neutrophil gelatinase-associated lipocalin (NGAL) in the spot urine samples. The changes in renal function, which were observed according to the serum creatinine level, showed that the renal function was preserved with a significant difference in the rhEPO administration group. The liver deviation enzymes, which had also shown increases in the serum as well as the occurrence of renal dysfunction, showed clear decreases in the serum, even though changes with a significant difference were not observed in the rhEPO administration group. The active oxygen did not show changes before and after ischemia-reperfusion nor changes due to the rhEPO administration. When examining the status of apoptosis in the tissues, apoptosis was shown to be inhibited due to the rhEPO administration. It is believed that the main preservation effects of rhEPO are the elimination of cytopathy/cell death, as derived from the resulting ischemic condition that extends to the target organ before ischemia occurs. In this examination, no direct effects of rhEPO administration on the emergence of active oxygen were observed. It is therefore suggested that there is a possibility of preserving the renal function in marginal donors with a longer agonal stage by effectively using rhEPO.

Malignant epithelioid angiomyolipoma of the kidney in a patient with tuberous sclerosis: an autopsy case report with p53 gene mutation analysis.

We report an autopsy case of malignant epithelioid angiomyolipoma in a 36-year-old male tuberous sclerosis patient. He had been diagnosed to have a bilateral renal tumor 20 years previously. The left kidney had been surgically resected at the age of 34, and the left renal tumor was pathologically diagnosed as classic angiomyolipoma and epithelioid angiomyolipoma. He suddenly died of cardiac arrest, and at autopsy the right kidney weighed 7120 g. The tumor presented with massive necrosis invading the inferior vena cava, but was not hemorrhagic. Microscopic examination revealed tumor cells varying in size with a predominantly solid proliferation pattern and marked atypical large cells with vesicular nuclei and abundant eosinophilic cytoplasm. Mitotic figures were often encountered, and atypical forms were also present. Metastatic lesions were identified in the right lung, liver, diaphragm, and mesentery. Immunohistochemical examination showed epithelioid angiomyolipoma cells that were focally reactive for HMB-45 and showed diffuse positive staining for Melan-A. No mutation was detected in the p53 gene by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis despite diffuse immunoreactivity for p53. This case was proven to be malignant because of the occurrence of distant metastases, and showed that p53 mutations are not always associated with malignant transformation in epithelioid angiomyolipoma.