Effects of six-cycle completion and earlier use of radium-223 therapy on prognosis for metastatic castration-resistant prostate cancer: A real-world multicenter retrospective study.

OBJECTIVES: To evaluate the effect of 6-cycle completion and earlier use of radium-233 dichloride (Ra223) on the prognosis of patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: We retrospectively evaluated 75 patients with bone metastases-predominant mCRPC who were treated with Ra223 between August 2016 and August 2021. The primary purpose of the study was to assess the effect of Ra223 completion (6 cycles) on patient prognosis, and the secondary purpose was to investigate factors associated with Ra223 incompletion (fewer than 6 cycles) and overall survival. RESULTS: The median age of the patients was 72 years. The median number of Ra223 administrations was 6 (interquartile range, 5-6), and the median Ra223 completion rate was 75%. The median time from mCRPC diagnosis to Ra223 administration was 17 months, and the median number of prior treatments was 2. Multivariable analysis indicated that unfavorable performance status (>0), prostate-specific antigen (PSA) level >10 ng/ml, extension of bone metastasis score 3 to 4, and Ra223 incompletion were significantly associated with poor overall survival. In addition, EOD 3 to 4 and 3 or more prior CRPC treatments were significantly associated with Ra223 incompletion. CONCLUSION: Six-cycle completion and earlier administration of Ra233 are potentially associated with favorable survival. Unfavorable factors (EOD 3-4 and ≥3 prior treatments) were significantly associated with Ra223 incompletion.

Trends in the use of neoadjuvant chemotherapy and oncological outcomes for high-risk upper tract urothelial carcinoma: a multicentre retrospective study.

OBJECTIVE: To evaluate temporal trends in neoadjuvant chemotherapy (NAC) utilisation and outcomes in patients with locally advanced upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: We included 289 patients from seven hospitals who underwent radical nephroureterectomy (RNU) for locally advanced UTUC (≥cT3 or cN+) between 2000 and 2020. These patients received RNU alone or two to four courses of NAC with either a cisplatin- or carboplatin-based regimen. We evaluated the temporal changes in NAC use and compared the visceral recurrence-free, cancer-specific, and overall survival rates. The effect of NAC on oncological outcomes was examined using multivariate Cox regression analysis with inverse probability of treatment weighting (IPTW) models. RESULTS: Of 289 patients, 144 underwent NAC followed by RNU (NAC group) and 145 underwent RNU alone (Control [Ctrl] group). NAC use increased significantly from 19% (2006-2010), 58% (2011-2015), to 79% (2016-2020). Pathological downstaging was significantly higher in the NAC group than in the Ctrl group. The IPTW-adjusted multivariable analyses showed that NAC significantly improved the oncological outcomes in the NAC group compared with the Ctrl group. Moreover, carboplatin-based NAC significantly improved the oncological outcomes in the NAC group compared with the Ctrl group among patients with chronic kidney disease Stage ≥3. There were no significant differences in oncological outcomes between the cisplatin- and carboplatin-based regimens. CONCLUSIONS: The use of NAC for high-risk UTUC increased significantly after 2010. Platinum-based short-term NAC followed by immediate RNU may not impede and potentially improves oncological outcomes.

Presurgical axitinib therapy increases fibrotic reactions within tumor thrombus in renal cell carcinoma with thrombus extending to the inferior vena cava.

BACKGROUND: Clinical benefits of presurgical axitinib therapy for renal cell carcinoma (RCC) extending into the inferior vena cava (IVC) remain unclear. We aimed to investigate surgical benefits and pathological antitumor effects of presurgical axitinib therapy for RCC with IVC thrombus. METHODS: Of 56 consecutive RCC patients with IVC thrombus between January 1994 and December 2016, 41 patients who underwent radical nephrectomy (RN) were categorized as upfront RN (Upfront group) or presurgical axitinib followed by RN (Presurgical group). We retrospectively evaluated safety, radiologic tumor responses, and Ki-67 proliferation index before and after axitinib administration in the Presurgical group. Surgical outcomes, postoperative complications, and fibrosis within the IVC thrombus were compared between the Upfront and Presurgical groups. RESULTS: The number of patients in the Upfront and Presurgical groups was 31 and 10, respectively. Major presurgical axitinib-related adverse events were grade 2 or 3 hypertension (50%). The median radiological tumor response in the renal tumor, IVC thrombus length, and IVC thrombus volume were -19%, -21 mm, and -54%, respectively. The fibrosis within the IVC thrombus was significantly higher in the Presurgical group (10%) than in the Upfront group (3.4%). The Ki-67 proliferation index was significantly decreased in RN specimens (7.3%) versus needle biopsy specimens (23%) in the Presurgical group. Blood loss and operative duration were significantly lower and shorter, respectively, in the Presurgical group than in the Upfront group. CONCLUSIONS: Presurgical axitinib therapy enhanced tumor reduction accompanied by fibrosis and may contribute to surgical risk reduction for selected patients.

Platinum-based Neoadjuvant Chemotherapy Improves Oncological Outcomes in Patients with Locally Advanced Upper Tract Urothelial Carcinoma.

BACKGROUND: Neoadjuvant chemotherapy (NAC) use for patients with locally advanced upper tract urothelial carcinoma (UTUC) is debatable. OBJECTIVE: To investigate the efficacy and safety of platinum-based NAC for locally advanced UTUC. DESIGN, SETTINGS, AND PARTICIPANTS: Of 233 consecutive patients who underwent radical nephroureterectomy, 55 patients received NAC (NAC group) and 138 patients did not (Ctrl group). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The two arms (Ctrl vs NAC) were matched using propensity scores to minimize selection bias. We retrospectively evaluated tumor response, post-therapy pathological downstaging, lymphovascular invasion, Ki67 status, and prognosis between pair-matched patients. Multivariate Cox regression analysis was performed for independent factors for prognosis. RESULTS AND LIMITATIONS: We selected 51 pair-matched patients in each group. The regimens in the NAC group included gemcitabine and carboplatin, and gemcitabine and cisplatin. The median response rate in the NAC group was 28%. NAC-related adverse events were tolerable. Pathological downstaging of the primary tumor was significantly higher in the NAC group than in the Ctrl group. The MIB1 index (immunostaining for Ki67) was significantly higher in the NAC group. NAC for locally advanced UTUC significantly prolonged progression-free, cancer-specific, and overall survival. Multivariate Cox regression analysis using an inverse probability of treatment weighting method showed that NAC was selected as an independent predictor for prolonged cancer-specific survival. Limitations are the retrospective design and the small sample size. CONCLUSIONS: Platinum-based NAC for advanced UTUC potentially improves oncological outcomes. Further prospective studies are needed. PATIENT SUMMARY: Platinum-based neoadjuvant chemotherapy for locally advanced upper tract urothelial carcinoma was safe and potentially improves oncological outcomes. A carboplatin-based regimen may be used as an alternative in patients with impaired renal function.

Risk-stratified surveillance and cost effectiveness of follow-up after radical cystectomy in patients with muscle-invasive bladder cancer.

BACKGROUND: The recurrence risk stratification and the cost effectiveness of oncological surveillance after radical cystectomy are not clear. We aimed to develop a risk stratification and a surveillance protocol with improved cost effectiveness after radical cystectomy. RESULTS: Of 581 enrolled patients, 175 experienced disease recurrences. The pathology-based protocol presented significant differences in recurrence-free survival between normal- and high-risk patients, but the medical expense was high, especially in normal-risk (≤pT2pN0) patients. Cox regression analysis identified six factors associated with recurrence-free survival. Risk score-based 5-year follow-up was significantly more cost effective than the pathology-based protocol. MATERIALS AND METHODS: We retrospectively evaluated 581 patients with radical cystectomy for muscle-invasive bladder cancer at 4 hospitals. Patients with routine oncological follow-up were stratified into normal- and high-risk groups by a pathology-based protocol utilizing pT, pN, lymphovascular invasion, and histology. Cost effectiveness of the pathology-based protocol was evaluated and a risk-score-based protocol was developed to optimize cost effectiveness. Risk-scores were calculated by summing risk factors independently associated with recurrence-free survival. Patients were stratified by low-, intermediate-, and high-risk score. Estimated cost per one recurrence detection by the pathology and by risk-scores were compared. CONCLUSIONS: Risk-score-stratified surveillance protocol has potential to reduce over-evaluation after radical cystectomy without adverse effects on medical cost.

Preoperative chronic kidney disease predicts poor oncological outcomes after radical cystectomy in patients with muscle-invasive bladder cancer.

OBJECTIVE: To evaluate the impact of preoperative chronic kidney disease (CKD) on oncologic outcomes in muscle-invasive bladder cancer patients who underwent radical cystectomy. METHODS: A total of 581 patients who underwent radical cystectomy at four medical centers between January 1995 and February 2017 were examined retrospectively. We investigated oncologic outcomes, including progression-free, cancer-specific, and overall survival (PFS, CSS, and OS, respectively) stratified by preoperative CKD status (pre-CKD vs. non-CKD). We performed a Cox proportional hazards regression analysis using inverse probability of treatment weighting (IPTW) to evaluate the impact of preoperative CKD on prognosis and developed the prognostic factor-based risk stratification nomogram. RESULTS: Of the 581 patients, 215 (37%) were diagnosed with CKD before radical cystectomy. Before the background adjustment, PFS, CSS, and OS after radical cystectomy were significantly lower in the pre-CKD group compared to the non-CKD group. Background-adjusted IPTW analysis showed that preoperative CKD was significantly associated with poor PFS, CSS, and OS after radical cystectomy. The nomogram for predicting 5-year PFS and OS probability showed significant correlation with actual PFS and OS (c-index = 0.73 and 0.77, respectively). CONCLUSIONS: Muscle-invasive bladder cancer patients with preoperative CKD had a significantly lower survival probability than those without CKD.

Contrast media enhancement reduction predicts tumor response to presurgical molecular-targeting therapy in patients with advanced renal cell carcinoma.

BACKGROUND AND OBJECTIVE: A quantitative tumor response evaluation to molecular-targeting agents in advanced renal cell carcinoma (RCC) is debatable. We aimed to evaluate the relationship between radiologic tumor response and pathological response in patients with advanced RCC who underwent presurgical therapy. RESULTS: Of 34 patients, 31 underwent scheduled radical nephrectomy. Presurgical therapy agents included axitinib (n = 26), everolimus (n = 3), sunitinib (n = 1), and axitinib followed by temsirolimus (n = 1). The major presurgical treatment-related adverse event was grade 2 or 3 hypertension (44%). The median radiologic tumor response by RECIST, Choi, and CMER were -19%, -24%, and -49%, respectively. Among the radiologic tumor response tests, CMER showed a higher association with tumor necrosis in surgical specimens than others. Ki67/MIB1 status was significantly decreased in surgical specimens than in biopsy specimens. The magnitude of the slope of the regression line associated with the tumor necrosis percentage was greater in CMER than in Choi and RECIST. MATERIALS AND METHODS: Between March 2012 and December 2016, we prospectively enrolled 34 locally advanced and/or metastatic RCC who underwent presurgical molecular-targeting therapy followed by radical nephrectomy. Primary endpoint was comparison of radiologic tumor response among Response Evaluation Criteria in Solid Tumors (RECIST), Choi, and contrast media enhancement reduction (CMER). Secondary endpoint included pathological downstaging, treatment related adverse events, postoperative complications, Ki67/MIB1 status, and tumor necrosis. CONCLUSIONS: CMER may predict tumor response after presurgical molecular-targeting therapy. Larger prospective studies are needed to develop an optimal tumor response evaluation for molecular-targeting therapy.

Detecting asymptomatic recurrence after radical cystectomy contributes to better prognosis in patients with muscle-invasive bladder cancer.

The prognostic benefit of oncological follow-up to detect asymptomatic recurrence after radical cystectomy (RC) remains unclear. We aimed to assess whether routine follow-up to detect asymptomatic recurrence after RC improves patient survival. We retrospectively analyzed 581 RC cases for muscle-invasive bladder cancer at four hospitals between May 1996 and February 2017. All patients had regular follow-up examinations with urine cytology, blood biochemical tests, and computed tomography after RC. We investigated the first site and date of tumor recurrence. Overall survival in patients with recurrence stratified by the mode of recurrence (asymptomatic group vs. symptomatic group) was estimated using the Kaplan-Meier method with the log-rank test. Cox proportional hazards regression analysis via inverse probability of treatment weighting (IPTW) was used to evaluate the impact of the mode of diagnosing recurrence on survival. Of the 581 patients, 175 experienced relapse. Among those, 12 without adequate data were excluded. Of the remaining 163 patients, 76 (47%) were asymptomatic and 87 (53%) were symptomatic at the time of diagnosis. The most common recurrence site and symptom were lymph nodes (47%) and pain (53%), respectively. Time of overall survival after RC and from recurrence to death was significantly longer in the asymptomatic group than in the symptomatic group. A multivariate Cox regression analysis using IPTW showed that in the patients with symptomatic recurrence was an independent risk factor for overall survival after RC and survival from recurrence to death. Routine oncological follow-up for detection of asymptomatic recurrence contributes to a better prognosis after RC.

[Management of High-Risk Prostate Cancer and Left Ectopic Ureter Inserting into Seminal Vesicle with Ipsilateral Hypoplastic Kidney of a Young Patient : A Case Report].

A 44-year-old male patient visited our hospital with a chief complaint of macroscopic hematuria. Prostate biopsies were performed due to prostate specific antigen (PSA) 11.6 ng/ml, and he was diagnosed with Gleason score 5＋4 prostate cancer. Computed tomography showed a left hypoplastic kidney. T2- weighted magnetic resonance imaging showed the left ureter stump with ectopic insertion into the dilated left seminal vesicle. He was diagnosed with high-risk prostate cancer and left ectopic ureter inserting into the seminal vesicle with ipsilateral hypoplastic kidney. Laparoscopic left nephroureterectomy and open radical prostatectomy were performed.

Testicular metastasis of prostate cancer: a case report.

The incidence of secondary neoplasms of the testis during autopsies is approximately 2.5%. Although most secondary testicular metastases are due to prostate cancer, only a few patients with prostate cancer have clinically manifested testicular metastasis. We report the case of a prostate cancer patient with testicular metastasis who was diagnosed after the presence of a palpable mass in the right testis. A 56-year-old Japanese male presented to our hospital with an elevated serum prostate-specific antigen (PSA) level of 137 ng/ml. He was diagnosed with stage IV (T3N1M1b) prostate cancer and received androgen deprivation therapy, followed by various hormonal manipulations. His serum PSA level was undetectable for 1 year. No distant metastases were detected during imaging examinations. He received radiation therapy; however, his serum PSA level increased gradually. Four months later, he presented with right testicular swelling. Computed tomography revealed a heterogenous mass in the right testis and a right high inguinal orchiectomy was performed. Histopathological analysis showed that the right testis was infiltrated with metastatic adenocarcinoma with a Gleason score of 8. This is a rare case of right testicular metastasis in a patient with prostate cancer. Testicular metastasis of prostate cancer can be aggressive and metastasize.

Surgery without Blood Transfusion for Giant Paraganglioma in a Jehovah's Witness Patient.

A retroperitoneal tumor was identified in a 57-year-old female belonging to Jehovah's Witnesses during a health check. Subsequent examination led to the suspicion of a right pheochromocytoma. The patient wished to be treated by bloodless surgery and consulted our hospital after being refused surgery by several hospitals. She signed a liability waiver for blood transfusion refusal. After obtaining consent for diluted autotransfusion and preoperative administration of erythropoietin, the surgery was scheduled. The tumor was attached to the inferior vena cava and left renal vein and engulfed the right renal artery and vein. The tumor and right kidney were removed en bloc. Operative time was 8 h and 18 min, with 1,770 ml of blood loss. The histopathological diagnosis was paraganglioma with the normal adrenal gland within the border of the tumor. The patient was discharged from the hospital with no postoperative complications.

A Case of Malignant Pheochromocytoma Detected during Fertility Treatment.

We report a case of malignant pheochromocytoma in a 35-year-old Japanese woman during fertility treatment, successfully treated with surgical excision. The patient recovered without any postoperative problems, and plasma catecholamine levels normalized. At present, 18 months after the operation, there are no signs of relapse.

Prognosis of elderly Japanese patients aged ≥80 years undergoing hemodialysis.

Although the number of elderly patients requiring dialysis has increased, data regarding the prognosis of elderly patients undergoing hemodialysis are limited. In the present study, prognosis in Japanese hemodialysis patients aged ≥80 years was evaluated. From January 1988 to July 2013, 1144 consecutive patients with end-stage renal disease required renal replacement therapy at our institution; of these, 141 were aged ≥80 years. These patients' charts were retrospectively reviewed for relevant clinical variables and survival time. The life expectancies table from the National Vital Statistics database was used, and prognostic factors were assessed by multivariate analysis. In total, 107 deaths (76%) were recorded during the study period. The median survival time and estimated life-shortening period in the patients were 2.6 years and -5.3 years, respectively. Eastern Cooperative Oncology Group Performance Status and hemoglobin level were revealed as prognostic factors in the multivariate analysis. Estimates of prognosis and prognostic factors may provide useful information for physicians as well as elderly patients with end-stage kidney disease.