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.

[A Case of Autoimmune Acquired Factor XIII Deficiency Diagnosed from Recurrent Postoperative Bleeding].

The patient was a 79-year-old man with ureteroileal anastomotic stricture after a Bricker ileal conduit. Endourological treatment of stenosis was performed via percutaneous nephrostomy and ileal conduit. The patient experienced lower abdominal pain on the following day, and computed tomographic (CT) scan showed hematoma retention around the kidney and active bleeding from the renal artery branches. Transarterial embolisation (TAE) was performed and the bleeding was controlled. Two days later, there was a sudden progression of anemia and CT showed an increase in hematoma around the kidney. We subsequently performed nephrectomy for hemostasis. Five days later, the anemia progressed further. There was hematoma retention in the retroperitoneal cavity, and emergency laparotomy hemostasis was performed. Routine coagulation test results were normal. Heavy bleeding was observed several days after TAE and the possibility of coagulation factor XIII deficiency was considered. Factor XIII deficiency was confirmed by a low factor XIII activity level. The patient was given plasma-derived factor XIII. After receiving factor XIII replacement, factor XIII activity remained unchanged and the patient continued to bleed. Thereafter, a cross-mixing test was performed and the patient was diagnosed with autoimmune acquired factor XIII deficiency. Cortical steroids were administered to remove the factor XIII inhibitor. Steroid administration showed a rapid increase in factor XIII activity, and bleeding symptoms were no longer observed. In cases of serious bleeding of unknown cause with a normal coagulation profile, acquired factor XIII deficiency should be suspected and factor XIII activity measured.

[Incidence of Antiresorptive Agent-Related Osteonecrosis of the Jaw in Urologic Cancers].

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is a serious adverse event of bone resorption inhibitors (BRIs), such as zoledronic acid and denosumab. Based on the results of phase 3 clinical trials for BRIs, the frequency of ARONJ is 1 to 2%, but the actual frequency is presumed to be higher. We studied 143 patients with urologic cancers with bone metastases who were treated with zoledronic acid or denosumab at our hospital between April 2007 and March 2020. ARONJ occurred in 24 patients (16.8%) ; that is, 14 of the 113 patients (12.4%) who received zoledronic acid alone, 8 of the 24 patients (33.3%) who received denosumab alone, and 2 of the 6 patients (33.3%) who sequentially switched from zoledronic acid to denosumab. ARONJ was cured in 8 patients (33.3%), improved in 3 patients (12.5%), unchanged in 4 patients (16.7%), and worsened in 9 patients (37.5%). The frequency of ARONJ increased as the duration of BRI administration prolonged. Time-to-ARONJ was shorter in patients treated with denosumab than in patients treated with zoledronic acid. The occurrence of ARONJ may be underestimated; therefore, further studies are needed to investigate the actual frequency of ARONJ in Japan.

[A Case of Rapidly Growing Sarcomatoid Urothelial Carcinoma of the Renal Pelvis and Ureter].

75 year-old man followed up regularly for the treatment of lung cancer came to our hospital with a chief complaint of general malaise. Blood test results showed deterioration in the renal function, and computed tomography (CT) confirmed left hydronephrosis. He was admitted to the hospital with the diagnosis of obstructive pyelonephritis. Despite antibiotic therapy after the left ureteral stent placement, CT on day 19 of hospitalization showed an enlarged soft tissue shadow along the renal pelvis and ureter, which was suspected to be peripelvic urinary extravasation caused by stent occlusion. We decided that conservative treatment would not improve his condition and conducted surgical therapy considering the possibility of malignancy. Intraoperatively, viscous and fragile tumor affected the renal pelvis and ureter. The operation resulted in left nephrectomy because radical resection was impossible. The pathological diagnosis was sarcomatoid urothelial carcinoma of the renal pelvis with ureter origin. He died due to multipleorgan failureon day 20 after theope ration. Were port a caseof sarcomatoid urothelial carcinoma in the upper urinary tract that was difficult to diagnose preoperatively based on imaging studies.

[A Case of Renal Epithelioid Angiomyolipoma with Recurrence in the Abdominal Cavity].

A 37-year-old man with no symptoms or family history of tuberous sclerosis complex presented to our hospital with abdominal pain in 2013. Abdominal computed tomography (CT) revealed a rupture in the right renal angiomyolipoma (AML) having a maximum diameter of 7 cm. He had undergone a transarterial embolization. Follow-up CT showed an increase in the size of the right tumor to 11 cm, and therefore, right nephrectomy was performed in 2016. The diagnosis of epithelioid AML (EAML) was confirmed. In 2019, he was diagnosed with a solitary tumor near right-sided transverse colon, which was resected and showed recurrence of EAML. He was disease-free 6 months after surgery. EAML has malignant potential, with 30-50% of reported EAML cases resulting in local recurrence or distant metastasis. Previous recurrence or metastasis may occur 0.25-12 years postoperatively. Furthermore, multiple and unresectable recurrences or metastases, arising early in the postoperative period may lead to a poor outcome. Therefore, close and long-term follow-up is required.

[Post-Operative Urethral Stricture after Holmium Laser Enucleation of the Prostate].

Holmium laser enucleation of the prostate (HoLEP) is a safe and effective surgical procedure for patients suffering from comparatively larger benign prostatic hyperplasia. However, the rate of postoperative urethral stricture (POUS) is relatively high, which can render further invasive intervention. Here we assessed the POUS rate, riskfactors and outcomes in 206 patients with benign prostatic hyperplasia who underwent HoLEP at our hospital between January 2006 and December 2015. POUS was observed in 24 patients (11.7%). The rate of intraoperative urethral stricture was significantly higher in the patients with POUS (8 out of 24 patients, 33.3%) than in those without POUS (12 out of 186 patients, 6.6%). The odds ratio was 7.08, 95% and combination index (CI) was 2.53-19.9, p<0.001). The relative riskfor POUS based on intraoperative urethral stricture was 4.65 (95% CI : 2.28-9.48). The most common POUS site was external urethral orifice (12 out of 24 cases). The POUS onset was significantly earlier in patients with external urethral orifice than the other sites (p=0.0389). The site of postoperative stricture concurred with that of intraoperative stricture at a high rate (7 out of 8 patients). Significant differences were observed between patients with and without POUS within one month in international prostate symptom score, quality of life score and in Qmax after the operation, while they were improved by simple interventions such as bougie. In conclusion, we should consider the possibility of POUS when the patient had an intraoperative stricture in HoLEP.

Intravesical prostatic protrusion is not always the same shape: Evaluation by preoperative cystoscopy and outcome in HoLEP.

AIMS: To examine how morphological differences in intravesical prostatic protrusion (IPP) predict outcome of Holmium laser enucleation of prostate (HoLEP) treatment. METHODS: We analyzed 173 patients who had undergone HoLEP in our hospital. The protrusion shape was evaluated by outpatient preoperative flexible cystoscopy and classified into five groups: A, no protrusion; B, middle lobe only; C, unilateral lobe only; D, bilateral lobes; and E, B + C or B + D. Paired-match analysis that adjusted for preoperative International Prostate Symptom Score (IPSS) voiding/storage subscores and IPP was performed between the group with middle lobe protrusion (B + E) and the group without it (C + D). RESULTS: Type A prostate shape was found in 23 patients, type B in 14, type C in 31, type D in 71, and type E in 34. Groups with middle lobe protrusion (B and E) had better changes in the total IPSS (P < 0.05) and the IPSS storage subscore (P < 0.01). Pair matching identified 37 patients each with or without middle lobe protrusion. The group with middle lobe protrusion had significantly more improved total IPSS (-17.5 ± 7.5 vs -13.5 ± 8.3, P < 0.05) and IPSS storage subscore (-6.9 ± 3.4 vs -4.8 ± 3.3, P < 0.05) than did those without middle lobe protrusion. CONCLUSIONS: Patients with middle lobe protrusion had greater IPSS improvement after HoLEP than those having comparable-length IPP but without middle lobe protrusion. IPP is not always the same shape and should be clinically divided into at least two groups.

[Advanced Adenocarcinoma of the Bladder after Augmentation Gastrocystoplasty].

A 29-year-old woman had undergone gastrocystoplasty with Mitrofanoff appendicovesicostomy for urethral trauma at 9 years of age. Since then, she was being followed up for performing clean intermittent self-catheterization at regular intervals. Twenty years after the surgery, she presented with gross hematuria. Ultrasonographic findings revealed bilateral hydronephrosis. Cystoscopy and computed tomography (CT) revealed invasive bladder cancer with pelvic lymph node metastases. A biopsy confirmed the diagnosis of adenocarcinoma with signet ring cell carcinoma. Subsequently, neo-adjuvant combination chemotherapy with TS-1 and cisplatin (CDDP) was initiated, which was followed by open radical cystectomy with extended pelvic lymphadenectomy. The tumor was found to infiltrate from the anastomotic site into the entire native bladder and histopathological diagnosis was muscle invasive adenocarcinoma with neuroendocrine differentiation and lymph node metastasis (ypT3bN2). TS-1 was continued as adjuvant chemotherapy and the patient did not have any evidence of recurrence for 12 months postoperatively.