Hitoshi Masuda

Long-term Oncological Outcome and Risk Stratification in Men with High-risk Prostate Cancer Treated with Radical Prostatectomy

OBJECTIVE To evaluate the long-term oncological outcome of radical prostatectomy for patients with high-risk prostate cancer. METHODS Among 378 patients with prostate cancer who underwent radical prostatectomy at our hospital, 189 had high-risk prostate cancer defined as presenting with at least one of the following high-risk factors: prostate-specific antigen >20 ng/ml, clinical T3 and biopsy Gleason score ≥8. RESULTS The median follow-up was 8.1 years. Of all patients, 106 and 61 had one and two high-risk factors, respectively, and the remaining 22 had all three high-risk factors. Pathological examination of the prostatectomy specimens revealed organ-confined disease, specimen-confined disease and lymph node metastasis in 80 (42%), 102 (54%) and 22 (12%), respectively. The 10-year prostate-specific antigen failure-free and local progression-free survival rates were 48.5 and 87.6%, respectively. The 10-year cancer-specific and overall survival rates were 94.1 and 88.7%, respectively. The 10-year prostate-specific antigen failure-free survivals of patients with one, two and all three high-risk factors were 58.5, 39.9 and 22.7%, respectively (P = 0.0001). Of the 106 patients with one high-risk factor only, the high Gleason score group had the best 10-year prostate-specific antigen failure-free survival (69.1%); in particular, that of patients without Gleason grade 5 was 100% (P= 0.032). CONCLUSIONS Approximately half of patients with high-risk prostate cancer can be cured by radical prostatectomy without any adjuvant treatment. Radical prostatectomy for high-risk prostate cancer provides good long-term local cancer control and cancer-specific survival. In particular, radical prostatectomy for patients with only one high-risk factor can be considered a valuable therapeutic option as the first treatment.

Biomarkers to predict prognosis and response to checkpoint inhibitors

Nivolumab is a fully human immunoglobulin (Ig) G4 antibody that selectively inhibits the programmed death 1 (PD-1) immune checkpoint molecule, and has recently been launched for the treatment of renal cell cancer (RCC) in Japan. Based on its promising anti-tumor efficacy and manageable safety profile demonstrated in the phase III Checkmate 025 trial, nivolumab therapy is rapidly being introduced in metastatic RCC clinical practice. The phase Ia study of atezolizumab, which is a humanized anti-PD-ligand 1 (PD-L1) monoclonal IgG1 antibody, also demonstrated excellent treatment results. The identification of biomarkers to predict the response and side-effects of checkpoint inhibitor therapy is thus urgently needed. In this review, we introduce the current candidate biomarkers of immune checkpoint inhibitor therapy. Based on the mechanism of efficacy, the number of neoantigens and expression of major histocompatibility complex molecules are strong candidate biomarkers. Despite the various interference factors, PD-L1 expression can be considered a potential biomarker. In terms of clinical factors, serum clinical factors and severity of adverse events are examined. Although further implementation in prospective studies is necessary, if validated, these biomarkers can be utilized to measure therapeutic response and design treatment strategies for metastatic RCC.

Role of diffusion-weighted magnetic resonance imaging as an imaging biomarker of urothelial carcinoma.

Diffusion‐weighted magnetic resonance imaging is a type of functional imaging that is increasingly being applied in the management of upper tract urothelial carcinoma and bladder cancer. The image contrast is derived from differences in the Brownian motion of water molecules in tissues. The homogenous high signal intensity of upper tract urothelial carcinoma and bladder cancer on diffusion‐weighted magnetic resonance imaging provides helpful diagnostic information for the presence of cancerous lesions in a non‐invasive manner. Recently, growing evidence has emerged showing that diffusion‐weighted magnetic resonance imaging can serve as an imaging biomarker for characterizing cancer pathophysiology, because the signal reflects biophysical information about the tissues. Quantitative analysis by evaluating the apparent diffusion coefficient values potentially reflects the histological grade and the biological aggressiveness of urothelial carcinoma. The apparent diffusion coefficient value could be a biomarker predicting the clinical course of upper tract urothelial carcinoma and bladder cancer. In addition, in chemoradiotherapy‐based bladder‐sparing approaches against muscle‐invasive bladder cancer, the role of diffusion‐weighted magnetic resonance imaging for predicting the chemoradiosensitivity and for monitoring therapeutic response has been shown. Diffusion‐weighted magnetic resonance imaging is expected to improve the diagnostic accuracy, and this qualitative information might allow individualized treatment strategies for patients with urothelial carcinoma.

Stepwise algorithm using computed tomography and magnetic resonance imaging for diagnosis of fat-poor angiomyolipoma in small renal masses: Development and external validation

To develop a stepwise diagnostic algorithm for fat‐poor angiomyolipoma in small renal masses.

Skene's gland adenocarcinoma with intestinal differentiation: A case report and literature review: Skene's gland adenocarcinoma

Adenocarcinoma of Skenes gland (the female homolog to the male prostate) is extremely rare, with only a few cases reported. We present a case of Skenes gland adenocarcinoma with intestinal differentiation. The patient was a 69‐year‐old Japanese woman who was operated on for a recurrent tumor of the external ostium of the urethra. Histopathologically, the tumor showed glandular and cribriform patterns with a signet‐ring cell component in a mucus lake. Immunohistochemically, the tumor cells were positive for prostate specific acid phosphatase (PSAP), and AMACR, and negative for Nkx3.1 or prostate specific antigen (PSA). Although in situ lesion could not be discovered, positive immunostainings for Nkx3.1, PSAP, and androgen receptor in the remaining paraurethral glands around the tumor indirectly but strongly suggest that the tumor had originated from Skenes gland. This tumor also showed intestinal differentiation as suggested histologically and by positive immunostainings for CDX2, MUC2, and CK20, along with negative immunostaining for CK7. It is often very difficult to identify the origin of a female urethral carcinoma. In such cases, immunohistochemical features can be an essential clue to the origin. We therefore present this instructive case with a literature review.

A novel fusion of HNRNPA1–ALK in inflammatory myofibroblastic tumor of urinary bladder☆

Here, we report an inflammatory myofibroblastic tumor (IMT) of the urinary bladder with a novel HNRNPA1-ALK fusion. To the best of our knowledge, this is the first case of a tumor with HNRNPA1-ALK fusion. A 42-year-old Japanese man underwent total cystectomy because of an invasive urinary bladder tumor. Grossly, the tumor had invaded the peribladder fat tissue. Histologically, it comprised spindle neoplastic cells with intermingled inflammatory cells. Immunohistochemically, it was positive for ALK, SMA, desmin, cytokeratin, and vimentin, consistent with the immunohistochemical characteristics of IMTs. Fluorescence in situ hybridization demonstrated an ALK split, and the presence of HNRNPA1-ALK was revealed by RNA sequencing. We identified a novel transcript fusion of exon 2 of HNRNPA1 and exon 18 of ALK, resulting in ALK protein overexpression. These findings provide useful information on the biology and tumorigenesis of IMTs, thus facilitating the development of molecular-targeted therapeutics.

Ureteral Involvement Is Associated with Poor Prognosis in Upper Urinary Tract Urothelial Carcinoma Patients Treated by Nephroureterectomy: A Multicenter Database Study

BACKGROUND The prognostic significance of tumor location for patients with upper urinary tract urothelial carcinoma (UUT-UC) has been disputed. Several papers have reported that ureteral cancer is associated with worse prognosis. OBJECTIVE To investigate the prognostic significance of the presence of ureteral tumors in UUT-UC patients who underwent radical nephroureterectomy (RNU). DESIGN, SETTING, AND PARTICIPANTS In this multicenter retrospective study, 1068 eligible patients (median follow-up: 40 mo [interquartile range: 17-77 mo]) were divided into three groups based on tumor location: renal pelvic, ureteral, and both-regional (having both renal pelvic and ureteral tumors). The ureteral and both-regional groups were subsequently integrated into the ureteral involvement group to evaluate its prognostic impact. INTERVENTION All patients underwent RNU. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The prognostic impact of tumor location on survival was analyzed. RESULTS AND LIMITATIONS The renal pelvic, ureteral, and both-regional groups consisted of 507 (47.5%), 430 (40.3%), and 131 (12.3%) patients, respectively. The ureteral and both-regional groups had a higher rate of lymphovascular invasion and lymph node metastasis compared with the renal pelvic group. The renal pelvic and both-regional tumors presented more frequently with locally advanced stages (pT3/T4) compared with the ureteral tumors. The 5-yr cancer-specific survival (CSS) and progression-free survival (PFS) rates of patients in the ureteral (70.5% and 66.7%, respectively) and both-regional groups (64.8% and 57.8%, respectively) were significantly worse than those in the renal pelvic group (81.9% and 78.1%, respectively). In a multivariate analysis, the presence of ureteral involvement was a significant prognostic factor for CSS (hazard ratio [HR]: 1.50; p=0.006) and PFS (HR: 1.35; p=0.023). This study is inherently limited by the biases associated with its retrospective and multicenter design. CONCLUSIONS The presence of ureteral involvement had a significant impact on the survival of surgically treated UUT-UC patients associated with a poor prognosis. PATIENT SUMMARY We demonstrated that the ureteral involvement was associated with poor survival compared with patients with renal pelvic tumor only in upper urinary tract urothelial patients treated by nephroureterectomy.

Pfannenstiel laparoendoscopic reduced-port radical nephrectomy.

We previously reported cases of laparoendoscopic single‐site nephrectomy performed through an umbilical or pararectal incision. To improve cosmesis and operability, we performed three Pfannenstiel laparoendoscopic reduced‐port nephrectomies.

Long-term complete response of antiandrogen withdrawal syndrome in a patient with metastatic prostate cancer: A case report

Antiandrogen withdrawal syndrome (AWS) is a well-established phenomenon in prostate cancer treated with combined androgen blockade (CAB). AWS is generally defined as subjective and/or objective improvement following discontinuation of an antiandrogen. However, the duration of the AWS response is usually limited. In addition, a complete response is quite rare. We herein present the case of a patient who achieved complete response from AWS, with the duration of this response lasting for >6 years. A 72-year-old man with metastatic prostate cancer received CAB with a luteinizing hormone-releasing hormone analog and bicalutamide. In addition, for local cancer control, external beam radiation therapy (70 Gy) to the prostate was performed. Subsequently, the serum prostate-specific antigen (PSA) level reached a nadir (undetectable level). Four years later, the patients serum PSA level started to rise, and bicalutamide was discontinued to confirm AWS at a serum PSA level of 0.34 ng/ml. The PSA level immediately decreased again to an undetectable level (0.00 ng/ml), where it has been remained for 6 years. Bone scintigraphy and computed tomography scans have shown no evidence of bone or other metastases since the introduction of AWS. To the best of our knowledge, there have been no reports of such a long duration of complete response from AWS. Therefore, this phenomenon should always be considered, even in patients with advanced disease.

Editorial Comment to Anti-oxidant activity and attenuation of bladder hyperactivity by the flavonoid compound kaempferol

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