A novel prognostic model of de novo metastatic hormone-sensitive prostate cancer to optimize treatment intensity.

BACKGROUND: The treatment and prognosis of de novo metastatic hormone-sensitive prostate cancer (mHSPC) vary. We established and validated a novel prognostic model for predicting cancer-specific survival (CSS) in patients with mHSPC using retrospective data from a contemporary cohort. METHODS: 1092 Japanese patients diagnosed with de novo mHSPC between 2014 and 2020 were registered. The patients treated with androgen deprivation therapy and first-generation anti-androgens (ADT/CAB) were assigned to the Discovery (N = 467) or Validation (N = 328) cohorts. Those treated with ADT and androgen-receptor signaling inhibitors (ARSIs) were assigned to the ARSI cohort (N = 81). RESULTS: Using the Discovery cohort, independent prognostic factors of CSS, the extent of disease score ≥ 2 or the presence of liver metastasis; lactate dehydrogenase levels > 250U/L; a primary Gleason pattern of 5, and serum albumin levels ≤ 3.7 g/dl, were identified. The prognostic model incorporating these factors showed high predictability and reproducibility in the Validation cohort. The 5-year CSS of the low-risk group was 86% and that of the high-risk group was 22%. Approximately 26.4%, 62.7%, and 10.9% of the patients in the Validation cohort defined as high-risk by the LATITUDE criteria were further grouped into high-, intermediate-, and low-risk groups by the new model with significant differences in CSS. In the ARSIs cohort, high-risk group had a significantly shorter time to castration resistance than the intermediate-risk group. CONCLUSIONS: The novel model based on prognostic factors can predict patient outcomes with high accuracy and reproducibility. The model may be used to optimize the treatment intensity of de novo mHSPC.

Boerhaave syndrome presenting black pleural effusion: A case report.

A 55-year-old man experienced nausea and vomiting after brushing his teeth. He experienced back pain after this episode and visited our emergency department. Chest computed tomography (CT) images revealed moderate pleural fluid accumulation and mild left pneumothorax. Thoracentesis showed black pleural effusion. Thoracic drainage included food debris with black pleural effusion, and gastroscopy revealed food debris and perforation of the lower esophagus. Esophageal perforation was surgically repaired using omental implantation and pleuroclysis. Given the high mortality rate associated with black pleural effusion, prompt diagnostic procedures and corresponding management are essential.

Utilization rate and long-term persistence of combination pharmacotherapy with ß3-agonists and antimuscarinics for overactive bladder refractory to monotherapy in a real-world setting.

AIM: To assess real-world treatment profiles, including utilization rate, time to and reasons for discontinuation of combination pharmacotherapy with ß3 -agonists and antimuscarinics for refractory overactive bladder (OAB) through a retrospective chart review. METHODS: We retrospectively reviewed the records of OAB patients who received ß3 -agonists or antimuscarinics at our hospital between 2012 and 2020 and analyzed the clinical course of patients who progressed to combination therapy. Data on age, sex, major complaints, OAB symptom score at the initiation of combination therapy, treatment persistence, and reasons for discontinuation were collected. Treatment persistence was assessed with respect to the median time to discontinuation and persistence rate at 12 months. RESULTS: Of the 2163 patients receiving ß3 -agonists or antimuscarinics, only 84 (3.8%) progressed to combination therapy with both drug classes. At therapy initiation, most (98%) of these patients had moderate to severe OAB symptoms. Median treatment duration and 12-month persistence rate for combination therapy were 595 days and 64.0%, respectively. The reasons for discontinuation were insufficient treatment efficacy followed by adverse effects including voiding impairment in nearly 10% of the patients. None of the baseline parameters was independently associated with persistence in the multivariate analysis. CONCLUSION: While underutilized among OAB patients refractory to monotherapy, combination pharmacotherapy showed a greater persistence rate than published mirabegron or antimuscarinic monotherapy when applied to patients with moderate to severe symptoms. Treatment-emergent voiding impairment is a concern associated with this mode of therapy. A small sample size at a single institution is the limitation of this study.

Overactive bladder medication: Persistence, drug switching, and reinitiation.

AIM: To assess real-world treatment profiles, including the time to and reasons for discontinuation or drug switching, treatment reinitiation, and postdiscontinuation follow-up in patients receiving antimuscarinics or ß3-agonists for overactive bladder (OAB) through a retrospective chart review. METHODS: We retrospectively reviewed medical charts of 777 patients, aged ≥18 years, who underwent antimuscarinic or ß3-agonist therapy at our hospital. Data on patient's age, sex, chief complaint, and OAB symptom score at therapy initiation were collected. Treatment persistence was assessed with respect to the median time to discontinuation and the persistence rate at 12 months. RESULTS: Older patients, male patients, and those with more severe urgency symptoms were more likely to show treatment persistence with OAB medications. Treatment persistence with mirabegron was significantly longer than that with antimuscarinics when administered as either the first- or second-line medication. Multivariate analyses showed that urgency severity and use of mirabegron were independently associated with better persistence (p = .026 and p = .018, respectively). Out of 583 patients who discontinued medication, 344 continued with the visit schedule, and the reinitiation rate of the OAB medication was 19% at a median follow-up of 24 months. CONCLUSION: Although the persistence rates for OAB medications improved with the introduction of mirabegron, most patients still discontinued the medication therapy within 1 year. The treatment strategies for patients with mild symptoms and those who are resistant to medication can still be improved. Tailored individualized treatments that avoid excessive reliance on pharmacotherapy would be key to further improve treatment outcomes in OAB patients.

[Initial Clinical Experience of Nivolumab for Metastatic Renal Cell Carcinoma].

Nivolumab was approved as a new agent for advanced renal cell carcinoma (RCC) in Japan on September 2016. Nivolumab is an immune checkpoint inhibitor that activates the cytotoxic immune response and has exerted antitumor effects in a mechanism different from other available molecular targeted agents. Therefore, its response pattern, efficacy and adverse events are different from those of the molecular targeted agents for RCC. Here, we report our initial clinical experience with nivolumab. From December 2016 to September 2017, we applied nivolumab to 7 patients with metastatic RCC. The most common metastatic site was the lungs, followed by lymph nodes, bones and brain. According to the immune-related response criteria, the efficacy was stable disease in 2 patients and progressive disease in 5 patients. In 5 cases with multiple metastases, responses differed with the site of metastasis. The response was best in lung metastasis and worst in brain metastasis. Six cases had minor adverse events. In two cases, we discontinued administration of nivolumab temporarily. The patients recovered completely and we considered nivolumab effective and safe for treatment of metastatic RCC.

[Prostate Cancer Diagnosed during Androgen Replacement Therapy for Late-Onset Hypogonadism Treatment: A Case Report].

We report a 60-year-old man with prostate cancer diagnosed during androgen replacement therapy (ART) for late onset hypogonadism after surgery for pituitary adenoma. He was refered to the department of urology since prostate specific antigen values were elevated after 6 months of ART. After the diagnosis of prostate cancer, ART was discontinued, and robot-asssited laparoscopic radical prostatectomy with pelvic lymphadenoctomy was performed. Pathological examination revealed Gleason score 4 + 5 prostate adenocarcinoma with seminal vesicle invasion and lymph node metastasis(pT3bN1). He has stayed biochemically and radiologically disease-free 33 months postoperatively.

[Reactive Arthritis during the Second Course of Intravesical BCG Therapy Requiring Administration of Methotrexate : A Case Report].

Reactive arthritis, formerly called Reiter's syndrome, is one of the rare complications following intravesical instillation of Bacillus Calmette Guerin (BCG). A 58-year-old man was admitted to our hospital because of fever, hyperemia of conjunctiva, and arthralgia following the second course of intravesical instillation of BCG in the treatment of pT1 and pTis bladder cancer. We diagnosed him with reactive arthritis due to the clinical course. Reactive arthritis is usually well controlled with the discontinuation of instillation and administration of nonsteroidal anti-inflammatory drugs (NSAIDs). However, his symptoms were not improved after administration of NSAIDs, prednisolone, and isoniazid. Following initiation of methotrexate, however, there was remission. He has been free from recurrence of bladder cancer for 20 months.

[Port-Site Metastasis of Prostate Cancer after Robot-Assisted Laparoscopic Prostatectomy : A Case Report].

The incidence of port-site metastasis in urologic laparoscopic surgery is low, especially in prostate cancer, with 4 reported cases to date. A 65-year-old man was introduced to our hospital presenting with gross hematuria and dysuria. His prostate-specific antigen (PSA) level was 3.1 ng/ml. He was diagnosed with poorly differentiated adenocarcinoma of the prostate, Gleason 9 (5＋4), cT3aN0M0 with non-invasive urothelial cancer of bladder (pTaN0M0, low grade). Robot-assisted laparoscopic prostatectomy was performed. Histopathological examination revealed adenocarcinoma, Gleason 9 (5＋4), pT3bN0, and surgical margins were positive. Eighteen weeks postoperatively, local recurrence, lymph node metastases, and a port-site metastasis were observed. Androgen deprivation therapy with 4 courses of induction docetaxel chemotherapy achieved a complete response on imaging study, 2 years postoperatively.

Seminoma in a Man with Russell-Silver Syndrome Presenting with Testicular Torsion.

Russell-Silver syndrome (RSS) is a type of primordial dwarfism. Only one case of testicular cancer in RSS has been reported, the pathology of which was nonseminoma. Here, we report a case of seminoma in a 36-year-old man who was diagnosed with RSS at birth. The seminoma was diagnosed when the patient presented with testicular torsion. This is the first report of testicular seminoma in an RSS patient in the literature. We also discussed the correlation between seminoma and RSS.