Association between Immune Checkpoint Inhibitor Treatment Outcomes and Body Composition Factors in Metastatic Renal Cell Carcinoma Patients.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic renal cell carcinoma (mRCC); however, validating body composition-related biomarkers for their efficacy remains incomplete. We evaluated the association between body composition-related markers and the prognosis of patients with mRCC who received ICI-based first-line therapies. PATIENTS AND METHODS: We retrospectively investigated 60 patients with mRCC who underwent ICI-based therapy as their first-line treatment between 2019 and 2023. Body composition variables, including skeletal muscle, subcutaneous fat, and visceral fat indices, were calculated using baseline computed tomography scans. Sarcopenia was defined according to sex-specific cut-off values of the skeletal mass index. The associations between body composition indices and objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated. RESULTS: Patients with sarcopenia had lower ORR and DCR than those without sarcopenia (33.3% vs. 61.1%, p = 0.0436 and 52.4% vs. 94.4%, p = 0.0024, respectively). Patients with sarcopenia had a significantly shorter median PFS (14 months vs. not reached, p = 0.0020) and OS (21 months vs. not reached, p = 0.0023) than patients without sarcopenia did. Sarcopenia was a significant predictor of PFS (hazard ratio [HR], 4.31; 95% confidence interval [CI], 1.65-14.8; p = 0.0018) and OS (HR, 5.44; 95% CI, 1.83-23.4; p = 0.0013) along with poor IMDC risk. No association was found between the subcutaneous, visceral, and total fat indices and the therapeutic effect of ICI-based therapy. CONCLUSIONS: Sarcopenia was associated with a lower response and shorter survival rates in patients with mRCC who received first-line ICI-based therapy.

[A Case of Secondary Syphilis Mimicking a Penile Cancer with Lymph Node Metastases].

A 42-year-oldman visited our hospital because of gradually worsening penile swelling over 3 weeks. A hard mass on the glans was palpated; however, we were unable to observe it due to severe phimosis. Magnetic resonance imaging of the pelvis revealed enlargement of glans and swelling of bilateral inguinal lymph nodes as both showed a low signal intensity on T2-weightedimaging, a high signal intensity on diffusion-weighted imaging, and a low signal intensity on the apparent diffusion coefficient map. Fluorine- 18-deoxyglucose (FDG) positron emission tomography showed FDG uptake at the external iliac, common iliac, obturator, and cervical lymph nodes besides the glans and inguinal lymph nodes. Although his serum squamous cell carcinoma antigen level was within the normal range, his soluble interleukin-2 receptor concentration was elevated to 2,290 U/ml. Therefore, we diagnosed these lesions as penile cancer with multiple lymph node metastases, with a possible differential diagnosis of malignant lymphoma. We planned a penile needle biopsy; however, the rapid plasma reagin test and treponema pallidum hemagglutination test, which were performed during the preoperative examination, were positive and led to a diagnosis of secondary syphilis. The patient was treated with oral amoxicillin at 1,500 mg/day for 8 weeks. The penile and lymph node swelling subsided after starting medication.

Transperitoneal laparoscopic umbilical resection of urachal remnants: a feasible surgical method.

BACKGROUND: To date, there is no standard established laparoscopic surgical method for managing urachal remnants because of their rarity, and several questions remain unanswered. Are there any problems for considering the operative indications about patients' factors for example, body mass index and so on? This study aimed to determine the feasible surgical method for managing urachal remnants and presents the operative outcomes of our cases in relation to the findings from the existing literature. METHODS: We analyzed the data of 16 patients (7 women and 9 men; age range, 19-48 years) who underwent surgery for urachal remnants between January 2013 and March 2019 at our institution. RESULTS: In our cases, all urachal remnants were urachal sinuses, and the primary complaints were umbilical pain and pus discharge. Most of these symptoms were controlled using umbilical drainage and oral antibiotic intake; however, incisional drainage was required in two cases. In all cases, we performed a laparoscopic resection of the urachal remnants; one patient underwent an open conversion due to a very thick abdominal wall. Therefore, "peri-umbilical distanse" was proposed as an index to verify the periumbilical abdominal wall thickness. This index may clear the difficulties of the laparoscopic resection of the urachal remnunts. A postoperative complication-local infection that was treated using re-suturing-was observed in one patient. No adverse events occurred in the other cases. Our method was appropriate because it allowed for complete urachal resection with good cosmetic results, i.e., a small and natural scar appearance. Additionally, if bladder injury occurred, bladder re-suturing was easily possible because of the laparoscopic port's position. CONCLUSIONS: We present an feasible method for laparoscopic urachal resection. This method may be recommended for young patients with an peri-umbilical distanse of < 2 cm.

Prostate-specific antigen kinetics contributes to decision making for biopsy referral: the predictive implication for PSA retest in patients with elevated PSA levels.

Background: It is common to repeat prostate-specific antigen (PSA) measurements for men with PSA elevation before prostate biopsy. In this scenario, they may have considerable psychological distress in fear of the presence of cancer until retests. We assessed possible clinical factors causing transient PSA rise and explored the parameters predictive of subsequent PSA change. Methods: As interfering conditions, the history of ejaculation, bicycling, and any types of infections were assessed using the questionnaire. The pattern of PSA change was compared in association with the various clinical factors. Predictive significance of PSA kinetics such as coefficient of variation (CV) and PSA velocity (PSAV) for PSA values at retest was evaluated. Results: The rate of reversion to the normal range was 38.3% at retest. The rate of 12.8% of men showed a large increase by ≥20%, whereas 38.2% of men showed a large decline by ≥20% from the baseline. Men with younger age (≤60 years), small prostate (<20 cc), and prior history of ejaculation or infections showed significantly larger PSA decrease than their counterparts. Those with large CV or PSAV before the baseline more frequently showed PSA decrease below the age-specific cutoff or decline by ≥10% from the baseline at retest. These parameters associated with PSA kinetics had independent predictive values for relevant PSA change at retest. Conclusions: Ejaculation and any types of infections should be avoided before PSA tests. Men with large PSA fluctuation before the baseline are likely to show a significant PSA decrease at retest. This predictive information may help both physicians to determine whether to proceed to an immediate biopsy and patients to reduce their psychological burden.

Plasma progastrin-releasing peptide level shows different predictive profiles for treatment response by androgen receptor axis-targeted agents in patients with metastatic castration-resistant prostate cancer.

BACKGROUND: The neuroendocrine (NE) pathway cannot be ignored as a mechanism for castration-resistant prostate cancer (CRPC) progression. The neuromediator, gastrin-releasing peptide (GRP) may be involved in the aberrant activation of the normal androgen receptor (AR) and increased AR variants. This study focused on plasma levels of progastrin-releasing peptide (ProGRP) and examined the treatment outcomes with androgen receptor axis-targeted (ARAT) agents. METHODS: One hundred patients with metastatic CRPC were enrolled. Enzalutamide (ENZ) or abiraterone acetate/prednisone (AA/P) were administered to 50 patients each in a nonrandomized manner as a first-line or later choice. Plasma ProGRP levels were determined using a chemiluminescent enzyme immunoassay, and data were collected prospectively. The study endpoints were prostate-specific antigen (PSA) response and survival estimates. RESULTS: In the ENZ series, ProGRP levels correlated with the maximum PSA change from baseline (high ProGRP: -34.5% vs. low ProGRP: -85.7% p = .033). PSA progression-free survival (PFS), radiographic/symptomatic (r/s) PFS, and overall survival (OS) in patients with high ProGRP were significantly worse than those in patients with low ProGRP (median PSA-PFS: 3.3 vs. 10.0 months, p = .001, r/s PFS: 5.0 vs. 15.0 months, p < 0.001, and OS 17.5 vs. 49.0 months, p < .001, respectively). In addition, ProGRP showed an independent predictive value for all survival estimates in multivariate analyses. In the AA/P series, ProGRP levels did not correlate with the PSA change or predict PSA-PFS and r/s PFS, but they maintained a significant difference in OS (19.0 vs. 48.0 months, p = .003). CONCLUSIONS: Plasma ProGRP provides a consistent predictive value for OS in metastatic CRPC patients who underwent therapy with ARAT agents. Meanwhile, ProGRP showed different predictive profiles for PSA- and r/s PFS between ENZ and AA/P. These findings clinically suggest a mechanism for CRPC progression involving the NE pathway via the GRP. The underlying mechanism of different predictive profiles by the ARAT agent should be explored in future research.

Clinical Significance of 18F-fluorodeoxyglucose and Glucose Transporter 1 mRNA in Clear Cell Renal Cell Carcinoma.

BACKGROUND/AIM: 18F-fluorodeoxyglucose (FDG) uptake measurement on positron emission tomography/computed tomography (PET/CT) is difficult in renal tumors because of the nearby renal parenchyma and urinary tract, which excrete FDG. We carefully examined the maximum standardized uptake value (SUVmax) on FDG-PET/CT and investigated the relationship between major glucose transporters in the kidney and clear cell renal cell carcinoma (ccRCC) progression. PATIENTS AND METHODS: Forty-five patients with ccRCC underwent FDG-PET/CT for staging and nephrectomy. Glucose transporter mRNA expression was examined in the removed kidney. RESULTS: SUVmax was increased in high-stage and high-grade tumors. Glucose transporter 1 (GLUT1) mRNA expression was higher in tumor tissues, in contrast to other glucose transporters. SUVmax was not correlated with GLUT1 mRNA expression. Kaplan-Meier analysis showed reduced overall and recurrence-free survival in the high SUVmax group. CONCLUSION: Primary ccRCC lesions show a high SUVmax and GLUT1 mRNA over-expression. SUVmax increases with tumor upstaging and upgrading.

Utility of whole-body diffusion-weighted magnetic resonance imaging in the management of treatment-related neuroendocrine prostate cancer.

INTRODUCTION: Treatment-related neuroendocrine prostate cancer, a rare and aggressive malignancy that emerges during androgen deprivation therapy characterized by low serum prostate-specific antigen concentrations, is challenging to monitor because it is associated with predominantly visceral and lytic bone metastases. CASE PRESENTATION: We describe the case of a 69-year-old man with treatment-related neuroendocrine prostate cancer in whom the treatment response could be monitored using whole-body diffusion-weighted magnetic resonance imaging in addition to serum concentrations of neuroendocrine markers. The patient responded well to platinum-based chemotherapy and achieved a complete response, as evidenced by these diagnostic modalities. CONCLUSION: Our case suggests that whole-body diffusion-weighted magnetic resonance imaging is useful in disease management for treatment-related neuroendocrine prostate cancer as well as the potential evaluation of mixed responses and treatment resistance.

Association of cancer progression with elevated expression of programmed cell death protein 1 ligand 1 by upper tract urothelial carcinoma and increased tumor-infiltrating lymphocyte density.

BACKGROUND: Increased expression of programmed cell death 1 ligand 1 (PD-L1) by tumor cells is thought to be a mechanism through which solid cancers promote immune tolerance. However, the association between PD-L1 expression and the prognosis of upper urinary tract urothelial carcinoma (UTUC) remains unknown. METHODS: We examined immunohistochemical PD-L1 expression and the tumor-infiltrating lymphocyte density (TILD) in 79 patients with UTUC who underwent nephroureterectomy. We classified the tumors into four types based on the combination of PD-L1 expression and TILD, and studied the clinicopathological characteristics of these four tumor types. RESULTS: Elevated expression of PD-L1 by tumor cells and a higher TILD were associated with a worse histological grade, higher pT stage, and higher peripheral blood neutrophil-to-lymphocyte ratio. Elevated expression of PD-L1 by tumor cells, a higher TILD, and type I, III, or IV tumors with elevated expression of either PD-L1 or TILD showed a positive correlation with poorer differentiation and local invasion. These three variables were associated with shorter progression-free survival and overall survival in univariate analysis, but only the latter was an independent determinant according to multivariate analysis. The patients who had type II tumors with lower PD-L1 expression and a lower TILD showed more favorable survival than the other three groups. CONCLUSIONS: These findings suggest that PD-L1 expression and TILs in the tumor microenvironment influence the progression of UTUC. Accordingly, it is important to understand the immunologic characteristics of the tumor microenvironment to develop more effective treatment strategies for this cancer.

Association between serum prostate-specific antigen level and diabetes, obesity, hypertension, and the laboratory parameters related to glucose tolerance, hepatic function, and lipid profile: implications for modification of prostate-specific antigen threshold.

BACKGROUND: Previous studies indicated inverse relationships between body mass index (BMI), diabetes and prostate-specific antigen (PSA) concentration besides an established positive relationship between age and PSA. Other causal relationships between clinical parameters including hypertension, hepatic function, tests, lipid profile and PSA were also suggested. Thus, we incorporated these parameters all together into the analysis to identify possible determinants of PSA concentration to improve the accuracy of PSA tests. METHODS: Associations between PSA and the above-mentioned clinical parameters were examined among 14,486 men who visited our hospital for a routine health checkup, using linear regression analyses. RESULTS: Total of 1403 (9.7%) and 784 (5.4%) men were classified as diabetes and obesity, respectively. After adjusting age, significant PSA reductions were found in diabetic men, especially for men taking antidiabetics. Such association was seen when the diabetic status was represented by hemoglobin A1c (HbA1c) and fasting blood sugar (FBS) levels. That is, PSA levels were significantly reduced in men with higher HbA1c and FBS levels. Obesity was also associated with a reduction in PSA levels. Moreover, PSA levels were significantly decreased with increased ALT levels. CONCLUSIONS: PSA test results should be carefully interpreted especially for men with diabetes and obesity, in whom a substantial reduction in PSA concentration is likely to occur.

Elevated serum levels of cardiovascular biomarkers are associated with progression of renal cancer.

Objective: Renal cell carcinoma (RCC) is a hypervascular tumour due to high constitutive production of vascular endothelial growth factor (VEGF), which is activated by hypoxia-inducible factor (HIF). Elevated levels of cardiovascular peptides, including brain natriuretic peptide (BNP), have been reported in patients with cancer, regardless of whether they have overt cardiovascular disease. Furthermore, it has been demonstrated that hypoxia stimulates BNP production by an HIF-dependent manner. However, the clinical implications of such cardiovascular peptides in patients with RCC have not been assessed. Methods: In patients with clear cell RCC who underwent nephrectomy, we investigated the relationship between the serum level of BNP or N-terminal pro-BNP (NT-proBNP) and various clinicopathological characteristics, including serum VEGF and expression of BNP and HIF-2 alpha in the primary tumour. Results: Elevated preoperative serum levels of BNP, NT-proBNP and VEGF, as well as increased tumour expression of HIF-2 alpha, were associated with a worse performance status, local invasion, distant metastasis and shorter overall survival. HIF-2 alpha expression showed a positive correlation with the preoperative serum VEGF level, while there was no relation between the serum levels of BNP/NT-proBNP and VEGF or tumour expression of HIF-2 alpha. BNP expression was very low in both tumour tissues and normal kidney tissues. Serum levels of BNP, NT-proBNP and VEGF all decreased significantly after nephrectomy. Conclusions: Our findings suggested that the preoperative serum levels of BNP and NT-proBNP are markers of tumour progression, as well as indicators of subclinical functional and structural myocardial damage in patients with advanced RCC.

[Diagnostic Impact of 3D-CT with Retrograde Pyelography for Ureteropelvic Junction Obstruction : A Case Report].

A 26-year-old woman presented to our hospital with right costovertebral angle (CVA) pain. Ultrasonographyand computed tomography(CT) scan indicated right hydronephrosis, and MAG3 renogram showed an obstructed pattern in the right kidney. Enhanced CT scan revealed an ureteropelvic junction obstruction (UPJO) with an aberrant vessel. To clarifythe ureteropelvic junction (UPJ) structure in detail, we utilized 3D-CT with retrograde pyelography (RP), which further revealed the true pinhole ureteral stricture of UPJ unaffected bythe aberrant vessel.

Performance characteristics of prostate-specific antigen density and biopsy core details to predict oncological outcome in patients with intermediate to high-risk prostate cancer underwent robot-assisted radical prostatectomy.

BACKGROUND: Many urologic surgeons refer to biopsy core details for decision making in cases of localized prostate cancer (PCa) to determine whether an extended resection and/or lymph node dissection should be performed. Furthermore, recent reports emphasize the predictive value of prostate-specific antigen density (PSAD) for further risk stratification, not only for low-risk PCa, but also for intermediate- and high-risk PCa. This study focused on these parameters and compared respective predictive impact on oncologic outcomes in Japanese PCa patients. METHODS: Two-hundred and fifty patients with intermediate- and high-risk PCa according to the National Comprehensive Cancer Network (NCCN) classification, that underwent robot-assisted radical prostatectomy at a single institution, and with observation periods of longer than 6 months were enrolled. None of the patients received hormonal treatments including antiandrogens, luteinizing hormone-releasing hormone analogues, or 5-alpha reductase inhibitors preoperatively. PSAD and biopsy core details, including the percentage of positive cores and the maximum percentage of cancer extent in each positive core, were analyzed in association with unfavorable pathologic results of prostatectomy specimens, and further with biochemical recurrence. The cut-off values of potential predictive factors were set through receiver-operating characteristic curve analyses. RESULTS: In the entire cohort, a higher PSAD, the percentage of positive cores, and maximum percentage of cancer extent in each positive core were independently associated with advanced tumor stage ≥ pT3 and an increased index tumor volume > 0.718 ml. NCCN classification showed an association with a tumor stage ≥ pT3 and a Gleason score ≥8, and the attribution of biochemical recurrence was also sustained. In each NCCN risk group, these preoperative factors showed various associations with unfavorable pathological results. In the intermediate-risk group, the percentage of positive cores showed an independent predictive value for biochemical recurrence. In the high-risk group, PSAD showed an independent predictive value. CONCLUSIONS: PSAD and biopsy core details have different performance characteristics for the prediction of oncologic outcomes in each NCCN risk group. Despite the need for further confirmation of the results with a larger cohort and longer observation, these factors are important as preoperative predictors in addition to the NCCN classification for a urologic surgeon to choose a surgical strategy.

Extravasation of Urine Associated with Bilateral Complete Ureteral Duplication, Vesicoureteral Reflux and Benign Prostatic Hyperplasia.

We report a rare case of extravasation of urine, which may be associated with bilateral complete ureteral duplication, vesicoureteral reflux (VUR), and benign prostatic hyperplasia (BPH). A 71-year-old male presented with a complaint of right abdominal pain. An extravasation of urine was noted, and was improved by indwelling urethral catheterization. Transurethral resection of the prostate and the endoscopic subureteral injection of dextanomer/hyaluronic acid were performed for the treatment of BPH and VUR, respectively. The post-surgery recovery was successful.

Clinically significant association between the maximum standardized uptake value on 18F-FDG PET and expression of phosphorylated Akt and S6 kinase for prediction of the biological characteristics of renal cell cancer.

BACKGROUND: The relationship between the clinicopathological features and molecular changes associated with standardized uptake value (SUV) determined by Positron emission tomography (PET) with [18F] fluorodeoxyglucose (18F-FDG PET) in human renal cell carcinoma (RCC) has not been elucidated. On the other hand, overactivation of the phosphatidylinositol 3'kinase (PI3K), serine/threonine kinase Akt, and mammalian target of rapamycin (mTOR) pathway has been detected in a variety of human cancers, including RCC. So far, little is known about the relationship between the SUV and these proteins in human RCC. Thus, it is important to study the relevance of SUV with clinicopathological features in human RCCs from a molecular point of view. METHODS: Seventy-seven consecutive patients with RCC who underwent nephrectomy and pretreatment determination of the maximum SUV (SUVmax) by 18F-FDG PET were analyzed. We investigated the relationship between the SUVmax, phosphorylated-Akt (Ser-473) (pAkt(Ser-473)), phosphorylated-Akt (Thr-308) (pAkt(Thr-308), and phosphorylated-S6 ribosomal protein (Ser-235/236) (pS6) protein levels in the primary tumor and various clinicopathological features. RESULTS: The average SUVmax of the primary tumor was 6.9 (1.5 to 40.3). A higher SUVmax was correlated with higher expression of pAkt(Ser-473), pAkt (Thr-308), and pS6 protein in the primary tumor. A higher SUVmax and increased expression of pAkt (Ser-473), pAkt (Thr-308), and pS6 of the primary tumor was associated with less tumor differentiation, a higher pT stage, regional lymph node involvement, microscopic vascular invasion, and distant metastasis, as well as with early relapse following radical nephrectomy in patients who had localized or locally advanced RCC without distant metastasis (cTanyNanyM0) and with shorter overall survival in all patients. CONCLUSIONS: A higher SUVmax on 18F-FDG PET is associated with elevated tumor levels of pAkt and pS6 protein and with aggressive behavior and metastatic potential of RCC, as well as with early relapse following radical nephrectomy and shorter overall survival. These findings suggest that SUVmax may be useful for predicting the biological characteristics of RCC.

Clinical significance of serum soluble T cell regulatory molecules in clear cell renal cell carcinoma.

To clarify the role of serum soluble T cell regulatory molecules in clear cell renal cell carcinoma (CCRCC), we measured the serum levels of soluble interleukin-2 receptor (sIL-2R), soluble B7-H3 (sB7-H3), and soluble cytotoxic T lymphocyte associated antigen-4 (sCTLA-4) in 70 CCRCC patients and 35 healthy controls. We investigated correlations between the serum levels of these soluble T cell regulatory molecules and the pathological grade, clinical stage, and prognosis of CCRCC. We also assessed the relations among each of these soluble molecules. As a result, the serum level of sIL-2R was significantly higher in CCRCC patients than in healthy controls (P < 0.05). In addition, elevation of serum sIL-2R was significantly correlated with the clinical stage (P < 0.001), and the survival of patients with high sIL-2R levels was shorter than that of patients with low sIL-2R levels (P < 0.05). Furthermore, the serum level of sB7-H3 was also significantly correlated with the clinical stage (P < 0.05), while the sIL-2R and sB7-H3 levels showed a positive correlation with each other (R = 0.550, P < 0.0001). These results indicate that the serum level of sIL-2R reflects tumor progression in CCRCC patients. In addition, the possibility was suggested that the IL-2/IL-2R and B7-H3 pathways may be involved in the progression of CCRCC.

The Rho-kinase inhibitor HA-1077 suppresses proliferation/migration and induces apoptosis of urothelial cancer cells.

BACKGROUND: Activation of Rho, one of the small GTPases, and its major downstream target Rho-kinase (ROCK) promotes the development and metastasis of cancer. We previously showed that elevation of Rho and ROCK expression was associated with tumor invasion, metastasis, and an unfavorable prognosis in patients with urothelial cancer of the bladder or upper urinary tract. METHODS: We investigated the effects of a ROCK inhibitor on the growth, migration, and apoptosis of bladder cancer cells. We also examined phosphorylation of RhoA (RhoA activity) by measuring its GTP-bound active form and assessed the expression of ROCK to explore the underlying molecular mechanisms. RESULTS: Lysophosphatidic acid (LPA) and geranylgeraniol (GGOH) induced an increase of cell proliferation and migration in association with promotion of RhoA activity and upregulation of ROCK expression. The ROCK inhibitor fasudil (HA-1077) suppressed cell proliferation and migration, and also induced apoptosis in a dose-dependent manner. HA-1077 dramatically suppressed the expression of ROCK-I and ROCK-II, but did not affect RhoA activity. CONCLUSIONS: These findings suggest that ROCK could be a potential molecular target for the treatment of urothelial cancer.

Prostate volume and biopsy tumor length are significant predictors for classical and redefined insignificant cancer on prostatectomy specimens in Japanese men with favorable pathologic features on biopsy.

BACKGROUND: Gleason pattern 3 less often has molecular abnormalities and often behaves indolent. It is controversial whether low grade small foci of prostate cancer (PCa) on biopsy could avoid immediate treatment or not, because substantial cases harbor unfavorable pathologic results on prostatectomy specimens. This study was designed to identify clinical predictors for classical and redefined insignificant cancer on prostatectomy specimens in Japanese men with favorable pathologic features on biopsy. METHODS: Retrospective review of 1040 PCa Japanese patients underwent radical prostatectomy between 2006 and 2013. Of those, 170 patients (16.3%) met the inclusion criteria of clinical stage ≤ cT2a, Gleason score (GS) ≤ 6, up to two positive biopsies, and no more than 50% of cancer involvement in any core. The associations between preoperative data and unfavorable pathologic results of prostatectomy specimens, and oncological outcome were analyzed. The definition of insignificant cancer consisted of pathologic stage ≤ pT2, GS ≤ 6, and an index tumor volume < 0.5 mL (classical) or 1.3 mL (redefined). RESULTS: Pathologic stage ≥ pT3, upgraded GS, index tumor volume ≥ 0.5 mL, and ≥ 1.3 mL were detected in 25 (14.7%), 77 (45.3%), 83 (48.8%), and 53 patients (31.2%), respectively. Less than half of cases had classical (41.2%) and redefined (47.6%) insignificant cancer. The 5-year recurrence-free survival was 86.8%, and the insignificant cancers essentially did not relapse regardless of the surgical margin status. MRI-estimated prostate volume, tumor length on biopsy, prostate-specific antigen density (PSAD), and findings of magnetic resonance imaging were associated with the presence of classical and redefined insignificant cancer. Large prostate volume and short tumor length on biopsy remained as independent predictors in multivariate analysis. CONCLUSIONS: Favorable features of biopsy often are followed by adverse pathologic findings on prostatectomy specimens despite fulfilling the established criteria. The finding that prostate volume is important does not simply mirror many other studies showing PSAD is important, and the clinical criteria for risk assessment before definitive therapy or active surveillance should incorporate these significant factors other than clinical T-staging or PSAD to minimize under-estimation of cancer in Japanese patients with low-risk PCa.

Axitinib for preoperative downstaging of renal cell carcinoma with sarcomatoid differentiation and direct invasion of the duodenum and inferior vena cava: a case report.

BACKGROUND: Renal cell carcinoma (RCC) with sarcomatoid differentiation is invasive, refractory to treatment, and has a higher mortality. Therefore, systemic therapy is still challenging, and the curative resection of localized or locally advanced RCC with sarcomatoid differentiation is very important. Axitinib is a potent and selective second-generation vascular endothelial growth factor receptor tyrosine kinase inhibitor with improved safety and tolerability. Axitinib is generally recommended as second-line therapy for advanced RCC because the phase III axitinib versus sorafenib in advanced RCC (AXIS) trial demonstrated that it achieved longer progression-free survival than sorafenib in patients with metastatic RCC after failure of an approved first-line regimen. METHODS: We present a 73-year-old man who had a large (13 cm in diameter) right RCC with sarcomatoid differentiation that directly invaded the duodenum and inferior vena cava. The patient presented with gastrointestinal bleeding, was unable to eat solid food, and had become emaciated. Thus, his classification was poor risk with anemia, hypercalcemia, and poor performance status, according to the Memorial Sloan-Kettering Cancer Center criteria. He seemed unlikely to survive if radical nephrectomy, cavotomy with thrombectomy, and pancreatoduodenectomy were performed. To reduce the tumor burden and potential operative complications, we administered axitinib as first-line neoadjuvant therapy. RESULTS: Six weeks of treatment reduced the tumor burden without causing severe toxicities. Subsequently, radical right nephrectomy, cavotomy with thrombectomy, and pancreatoduodenectomy were performed successfully. The pathological treatment effect of axitinib was grade 2 (two-thirds necrosis). The resected tumor showed a heterogeneous reaction for phosphorylated Akt (Ser-473) by Western blotting and immunohistochemistry, indicating that parts of the tumor were sensitive to axitinib and other parts were not. CONCLUSION: Axitinib might be promising as preoperative or neoadjuvant therapy for locally advanced RCC (>cT3b or >cTanyN1).

Metronomic oral cyclophosphamide chemotherapy possibly contributes to stabilization of disease in patients with metastatic castration-resistant prostate cancer: a prospective analysis of consecutive cases.

INTRODUCTION/BACKGROUND: Castration-resistant prostate cancer remains a therapeutic challenge, even after establishing the survival benefits of docetaxel chemotherapy. Metronomic chemotherapy stabilizes various cancers through antiangiogenic and immunomodulatory effects. We evaluate the activity of metronomic oral cyclophosphamide chemotherapy in metastatic CRPC patients, and assess predictive factors for clinical outcomes. PATIENTS AND METHODS: Twenty-four patients with metastatic CRPC received an oral cyclophosphamide and dexamethasone regimen. Of those, 11 patients (45.8%) had been exposed and resistant to previous docetaxel chemotherapy. Six patients had refused to receive docetaxel chemotherapy, and 7 patients could not receive the therapy because of deteriorated performance status. All patients had already shown resistance to continuous dexamethasone therapy. Demographic and clinical data were collected prospectively. RESULTS: A total of 16 patients (66.7%) experienced a reduction in PSA levels, and PSA decrease ≥ 50% was observed in 8 patients (33.3%). The median PSA progression-free and overall survival were 5.0 months and 19.0 months, respectively. The favorable PSA decrease had no associations with the progression-free and overall survival, but 7 patients (29.2%) in whom response had exceeded 8 months achieved long overall survival of 28 months in median. None of the patients discontinued therapy because of the presence of toxicities. CONCLUSION: Metronomic cyclophosphamide is an active and well tolerated chemotherapy and can be an option for metastatic CRPC patients. The benefit of this regimen could not always be evaluated according to a favorable PSA decrease; thus, we must identify the predictive factors of response other than known clinical factors.