Double Primary Cancer of the Prostate and Urothelial Cancer: A Single Institution Experience.

Prostate cancer (PCa) ranks as the second most common cancer in Japanese males, while bladder cancer (BC) holds the tenth spot. Among double urological cancers, the incidence of synchronous or metachronous BC and PCa is the highest. Reports on upper urinary tract (UUT) urothelial cancer (UC) in PCa patients are limited. Here, we present three cases of metachronous PCa and BC, with subsequent diagnosis of ureteral and renal pelvic cancer during the course of the disease. In the follow-up of patients with urological cancers, it is important to be aware not only of the progression of the initial cancer but also the potential development of a second cancer.

Trends in the use of local intervention for metastatic hormone-naïve prostate cancer: A multicenter retrospective study.

OBJECTIVE: To evaluated the trends of local intervention and their impact on oncological outcomes in metastatic hormone-naïve prostate cancer (mHNPC) in real-world practice. METHODS: This retrospective multicenter study included 760 patients treated with either androgen deprivation therapy (ADT) without local treatment (no castration-resistant prostate cancer [CRPC] progression within 12 months, control group) or ADT plus local intervention (intervention group) between January 2005 and March 2022. We evaluated the trends in the use of local intervention in patients with mHNPC and factors associated with CRPC-free survival in the intervention group. RESULTS: The use of local intervention gradually increased in combination with upfront combination treatment (docetaxel or androgen receptor axis-targeted agents) for the duration of our study. The number of patients with local intervention combined with upfront treatment was significantly higher in patients with high tumor burden disease than in those with low tumor burden disease. Of the 108 patients who received local intervention, a duration of ≤7 months of initial therapy before local intervention and a level of prostate-specific antigen ≥0.20 ng/mL at the time of local intervention were significantly associated with poor CRPC-free survival. CONCLUSIONS: The use of local intervention in combination with upfront therapy to treat mHNPC increased for the duration of our study regardless of the tumor burden. Local intervention in addition to the standard of care for mHNPC may be a feasible treatment option for selected patients, taking into consideration the duration of and response to initial treatment.

Megalourethra and bladder foreign body in a female patient.

Key Clinical Message: Undiagnosed female megalourethra can be a cause of iatrogenic bladder foreign body. Abstract: Foreign bodies in the urinary bladder are relatively rare. Female megalourethra is an extremely rare congenital disorder which is usually associated with Müllerian anomalies. We describe a case of an iatrogenic bladder foreign body and a megalourethra in a young woman with normal gynecological organs.

Incidental detection of localized prostate cancer with low PSA by computed tomography scan: A report of two cases.

Serum prostate-specific antigen (PSA) levels play an important role in the screening and diagnosis of prostate cancer (PCa). The recommended PSA cut-off in PCa screening is 4 ng/ml. We report two cases of localized PCa with low PSA levels that were incidentally found by computed tomography (CT) performed for another disease.

Effect of upfront intensive therapy on oncological outcomes in older patients with high tumor burden metastatic castration-sensitive prostate cancer: A multicenter retrospective study.

BACKGROUND: The effect of upfront intensive therapy on the prognosis of older patients with metastatic castration-sensitive prostate cancer (mCSPC) remains unclear. Thus, we assessed the impact of older age (≥75 years) on oncological outcomes in mCSPC patients with a high tumor burden. METHODS: This multicenter retrospective study included 252 patients aged ≥75 years treated with either upfront or conventional therapy between 2014 and 2021. We compared castration-resistant prostate cancer (CRPC)-free survival (FS) and overall survival (OS) between patients with androgen deprivation therapy (ADT) plus upfront intensive therapy (docetaxel [DTX] or abiraterone acetate [ABI] plus prednisolone) and conventional therapy (ADT monotherapy or ADT combined with bicalutamide). We evaluated the effect of upfront intensive therapy on prognosis by multivariable Cox regression analysis. RESULTS: The 231 patients enrolled in our study were classified in the conventional group (n = 148) or the upfront group (n = 104; DTX = 27 and ABI = 77). The upfront group had significantly prolonged CRPC-FS and OS compared with the conventional group, and this was also the case in the background-adjusted multivariable Cox regression analysis. CONCLUSION: Patients aged ≥75 years who received upfront intensive therapy had significantly longer CRPC-FS and OS compared with similar age patients treated with conventional therapy in real-world practice. The oncological benefit may not diminish in this older population.

Clinical response in metastatic castration-resistant prostate cancer (mCRPC) cases treated with supra-physiological doses of testosterone: Bipolar androgen therapy.

Androgen deprivation therapy is a standard of care for metastatic prostate cancer. A paradoxical approach utilizing high doses of testosterone in castration-resistant prostate cancer patients demonstrated clinical responses. Here, we report on four heavily pretreated Japanese patients (including one patient on hemodialysis) successfully treated with supra-physiological doses of testosterone.

Multiple endocrine disorders manifested as gynecomastia in a patient with renal pelvis cancer.

A 95-year-old man was diagnosed with left renal pelvis cancer which presented with rapid tumor growth, multiple metastases, and bilateral tender gynecomastia. Elevated serum human chorionic gonadotropin (hCG), prolactin, estradiol, and progesterone were detected. The patient's condition rapidly deteriorated, and he passed away.

Impact of Gleason pattern 5 on prognosis for newly diagnosed metastatic hormone-sensitive prostate cancer with Gleason score ≥8.

OBJECTIVE: We evaluated the impact of Gleason pattern 5 presence on prognosis among de novo metastatic hormone-sensitive prostate cancer patients with a Gleason score ≥8. METHODS: The data of 559 patients diagnosed as metastatic hormone-sensitive prostate cancer with a Gleason score ≥8, who were initially treated with androgen deprivation therapy from 2008 to 2016, were retrospectively collected. Patients were divided into two groups as high and low volume based on the CHAARTED trial criteria. RESULTS: The median overall survival of the 559 metastatic hormone-sensitive prostate cancer patients with Gleason score ≥8 was 70 months, with a median follow-up period of 36 months. Gleason pattern 5 was confirmed in 341 patients (61.0%), in which primary Gleason pattern 5 was confirmed in 164 patients (29.3%). The number of patients with high metastatic volume group was 363 (64.9%). In total and high metastatic volume groups, hemoglobin and lactate dehydrogenase were significant factors for predicting overall survival, but both Gleason pattern 5 and primary Gleason pattern 5 did not show a statistically significant difference. In the low-volume metastatic group, the median overall survival in patients with or without primary Gleason pattern 5 was 40 and 78 months, respectively. In multivariate analysis, only primary Gleason pattern 5 was an independent predictive factor for overall survival in the low-volume metastatic group (hazard ratio 2.76, 95% confidence interval 1.88-8.67; P = 0.0026). CONCLUSION: The presence of Gleason pattern 5 was not associated with overall survival in metastatic hormone-sensitive prostate cancer with a Gleason score ≥8. In low-metastatic volume metastatic hormone-sensitive prostate cancer, primary Gleason pattern 5 was a poor prognostic factor, which might show a separate treatment option for this group.

Prostatic urethra recurrence after transurethral resection of bladder tumor (TURBT) for non-muscle-invasive bladder cancer (NMIBC).

Urinary bladder cancer is frequently multifocal and has a high incidence of recurrence. Although the prostatic urethra is a frequent site of tumor relapse in patients with non-muscle-invasive bladder cancer treated with TURBT, such tumors are often underdiagnosed. Here we present two cases having urethral recurrence after TURBT.

Surgery to Avoid Stoma Construction in Invasive Prostate Cancer Extensively Infiltrating the Rectum.

A 61-year-old man tested positive for occult urinary and fecal occult blood and was diagnosed with invasive prostate cancer extensively infiltrating the rectum. After scrutiny, he was diagnosed with cT4N1M0 prostate cancer, and androgen deprivation therapy (ADT) was initiated with a gonadotropin-releasing hormone antagonist. A prostatic rectal resection was performed 6 months after ADT began. The bladder and urethra were anastomosed, the anus was preserved intact, and the sigmoid colon was anastomosed to the anus. A temporary ileostomy was constructed to allow eating and to prevent fistula formation. The ileostomy was closed 5 months post-operation as the patient wanted to live without a stoma. Although the patient died of other disease factors, he remained untreated for 1 year and 7 months post-operation, and his symptoms and disease control were well supported. We report that we were able to perform stoma-free surgical treatment for prostate cancer extensively infiltrating rectum.

[A Case of Upper Urinary Tract Stone in an Infant].

A 238-day-old female infant (122 days of age corrected for prematurity, weight 4,847 g) presented with macrohematuria. She was born at 23 weeks and3 days of pregnancy. Her birth weight was 492 g. Ultrasound revealeda 3×2 mm left ureteral stone and left hydronephrosis of grade I-II in the Society of Fetal Urology (SFU) Classification. She suffered from frequent vomiting and weight loss, and was treated with analgesics and rehydration. Eventually, left hydronephrosis was relieved, and she passed the stone at 271 days of age. The stone was 4×3×2 mm in size, and consisted of 98% calcium oxalate and2% calcium phosphate. No recurrent stone has been found during follow-up.

Impact of pretreatment anemia on upfront abiraterone acetate therapy for metastatic hormone-sensitive prostate cancer: a multicenter retrospective study.

BACKGROUND: Anemia has been a known prognostic factor in metastatic hormone-sensitive prostate cancer (mHSPC). We therefore examined the effect of anemia on the efficacy of upfront abiraterone acetate (ABI) in patients with mHSPC. METHODS: We retrospectively evaluated 66 mHSPC patients with high tumor burden who received upfront ABI between 2018 and 2020 (upfront ABI group). We divided these patients into two groups: the anemia-ABI group (hemoglobin < 13.0 g/dL, n = 20) and the non-anemia-ABI group (n = 46). The primary objective was to examine the impact of anemia on the progression-free survival (PFS; clinical progression or PC death before development of castration resistant PC) of patients in the upfront ABI group. Secondary objectives included an evaluation of the prognostic significance of upfront ABI and a comparison with a historical cohort (131 mHSPC patients with high tumor burden who received androgen deprivation therapy (ADT/complete androgen blockade [CAB] group) between 2014 and 2019). RESULTS: We found that the anemia-ABI group had a significantly shorter PFS than the non-anemia-ABI group. A multivariate Cox regression analysis showed that anemia was an independent prognostic factor of PFS in the upfront ABI group (hazard ratio, 4.66; P = 0.014). Patients in the non-anemia-ABI group were determined to have a significantly longer PFS than those in the non-anemia-ADT/CAB group (n = 68) (P < 0.001). However, no significant difference was observed in the PFS between patients in the anemia-ABI and the anemia-ADT/CAB groups (n = 63). Multivariate analyses showed that upfront ABI could significantly prolong the PFS of patients without anemia (hazard ratio, 0.17; P < 0.001), whereas ABI did not prolong the PFS of patients with anemia. CONCLUSION: Pretreatment anemia was a prognostic factor among mHSPC patients who received upfront ABI. Although the upfront ABI significantly improved the PFS of mHSPC patients without anemia, its efficacy in patients with anemia might be limited.

Therapeutic effects of the combined androgen blockade therapy versus luteinizing hormone-releasing hormone analog monotherapy in patients with hormone naïve metastatic prostate cancer: a multi-institutional comparative analysis.

BACKGROUND: The clinical benefit of the combined androgen blockade (CAB) therapy over luteinizing hormone-releasing hormone analog (LH-RHa) monotherapy for hormone naïve metastatic prostate cancer (mHNPC) is unclear. Therefore, we retrospectively compare the effectiveness of CAB with the LH-RHa monotherapy on the prognosis of Japanese patients with mHNPC. METHODS: We retrospectively evaluated the prognosis of 517 patients diagnosed with mHNPC between August 2001 and May 2017. The patients' data were obtained from the Michinoku Urological Cancer Research Group database and Hirosaki University-related hospitals. Patients were divided into the CAB and LH-RHa monotherapy groups based on primary androgen deprivation therapy (ADT). Overall survival (OS), cancer-specific survival (CSS), and castrate-resistant prostate cancer-free survival (CRPC-FS) were compared between the two groups using the Kaplan-Meier curve analysis. Inverse probability of treatment weighting (IPTW)-adjusted Cox hazard proportional analyses was performed to investigate the effect of primary ADT on oncological outcomes. RESULTS: The median age was 73 years old. The numbers of patients in the CAB and LH-RHa monotherapy groups were 447 and 70, respectively. The Kaplan-Meier curve analysis showed no significant differences in either 5-year OS (56.7% vs. 52.5%, P=0.277), CSS (61.1% vs. 56.4%, P=0.400), and CRPC-FS (33.1% vs. 31.1%, P=0.529) between the groups. IPTW-adjusted multivariate Cox hazard proportional analyses showed no significant differences in OS, CSS, and CRPC-FS between the two groups. CONCLUSIONS: No significant differences in oncological outcomes were observed between the CAB and LH-RHa monotherapy groups in patients with mHNPC.

[A Case of Testicular Tumor with Multiple Metastasis Leading to Complete Response after Treatment Interruption].

A 39-year-old man experiencing cranial nerve symptoms was referred to our neurosurgery department after a brain tumor was detected on computed tomography (CT) scans at a local hospital. Due to convulsive symptoms, the patient was admitted to our hospital for detailed examination. The patient was diagnosed with right testicular tumor, multiple brain metastases, multiple lung metastases and right kidney metastases, and was transferred to our urology department. Since the testicular tumor was staged as IIIC and identified as poor prognosis by the International Germ Cell Consensus classification (IGCCC), Bleomycin Etoposide Cisplatin (BEP) chemotherapy was initiated prior to surgery. A right high orchiectomy was performed after two courses of BEP chemotherapy. Histopathology revealed mixed germ cell tumors (seminoma and/or embryonal carcinoma+teratoma) along with the following results : ly (-) ; Intratubular Malignant Germ Cells (ITMGC) (+, viable) ; tunica albuginea invasion (-) ; spermatic cord invasion (-) ; tumor size (73× 50×45 mm). Two additional courses of BEP chemotherapy and two courses of Paclitaxel Ifomaide Cisplatin(TIP) chemotherapy were performed successively. The CT revealed metastatic lesions shrinking steadily but the metastatic foci still remained. Since tumor markers were not negative, continuous chemotherapy was considered. However, strong side effects were expected, and treatment was discontinued. Since then,the tumors continued to shrink, and the tumor markers became negative. Currently, the patient maintains complete response and is being followed-up.

Familial testicular germ cell tumors in two brothers.

INTRODUCTION: Two percent of testicular germ cell tumors occur in family clusters. Here, we report metachronous testicular germ cell tumors in two brothers. CASE PRESENTATION: An elder brother was diagnosed at the age of 30 years old and the pathological diagnosis was mixed testicular germ cell tumor. A tumor in the younger brother was suspected during testicular self-examination. It was confirmed by ultrasound examination at the age of 30 years old, 3 years and 6 months after the diagnosis of the testicular tumor in elder brother. The pathological diagnosis was pure seminoma. Both brothers had stage 1 testicular germ cell tumors and no recurrence was observed during the follow-up period of 4 years and 4 months and 10 months, respectively. CONCLUSION: Various histological types of tumor can occur in members of one family. Besides genetic predisposition, shared diet, environmental exposure and other factors can contribute to the familial testicular cancer. Testicular self-examination is recommended for family members of a person with testicular germ cell tumor.

Association of tumor burden with the eligibility of upfront intensification therapy in metastatic castration-sensitive prostate cancer: A multicenter retrospective study.

OBJECTIVES: To evaluate the association of tumor burden with the prognosis in real-world patients with metastatic castration-sensitive prostate cancer and to investigate the eligibility for upfront intensification therapy. METHODS: We retrospectively evaluated 679 patients with metastatic castration-sensitive prostate cancer who were initially treated with conventional androgen deprivation therapy between August 2001 and November 2018. The primary purpose was to investigate the eligibility for upfront intensification therapy based on the progression of metastatic castration-resistant prostate cancer. The secondary purpose included the comparison of the metastatic castration-resistant prostate cancer progression rate, metastatic castration-resistant prostate cancer-free survival and overall survival after castration-resistance in CHAARTED low- or high-volume disease patients. RESULTS: The number of patients with metastatic castration-resistant prostate cancer progression was 119 (52%) and 319 (71%) in the low- and high-volume disease groups, respectively. The metastatic castration-resistant prostate cancer progression rate (P < 0.001) and castration-resistant prostate cancer-free survival (P < 0.001) were significantly different between the low- and high-volume disease groups, but no difference was found for overall survival after castration resistance (P = 0.363). Multivariate Cox regression analysis showed no significant association between tumor burden and overall survival after castration resistance (P = 0.522; hazard ratio 1.14). CONCLUSIONS: The progression rate in metastatic castration-resistant prostate cancer patients with the low-volume disease under conventional androgen deprivation therapy is approximately 50%. Upfront intensification therapy might be beneficial for approximately half of patients with low-volume disease. A novel maker to predict the castration-resistant status is required to select optimal patients for upfront intensification therapy.

Clinical outcomes and prognostic factors in patients with newly diagnosed metastatic prostate cancer initially treated with androgen deprivation therapy: a retrospective multicenter study in Japan.

PURPOSE: Clinical outcomes of patients with newly diagnosed metastatic hormone-naïve prostate cancer (mHNPC) and initially treated with androgen deprivation therapy (ADT) were evaluated. METHODS: The medical records of 605 consecutive mHNPC patients with initial ADT or combined androgen blockade (CAB) at nine study centers between 2008 and 2016 were retrospectively reviewed. Castration-resistant prostate cancer (CRPC)-free and overall survival (OS) were estimated by the Kaplan-Meier method. The association of pretreatment risk factors with CRPC-free survival and OS was evaluated by Cox proportional hazard models and differences in survival were classified by the number of risk factors. RESULTS: Median follow-up was 2.95 years, median CRPC-free survival was 21.9 months and median OS was 5.37 years. Multivariable analysis found that four risk factors, a Gleason score ≥ 9, lymph node metastasis, an extent of disease score ≥ 2, and serum LDH of > 220 IU were independently associated with both CRPC-free survival and OS. Median CRPC-free survival of low-risk patients with no or one factor was 86.5 months, 17.9 months in intermediate-risk patients with two or three factors, and 11.0 months in high-risk patients with four factors. Median OS was 4.72 years in intermediate- and 2.44 years in high-risk patients. It was not reached in low-risk patients. CONCLUSION: In this series, CRPC-free and OS of a subset of mHNPC patients in Japan who were treated with ADT or CAB had better CRPC-free and overall survivals in Japan. Risk-adapted treatment based on the presence of novel prognostic factors may be beneficial for selected mHNPC patients.

The Effect of Treatment Sequence on Overall Survival for Men With Metastatic Castration-resistant Prostate Cancer: A Multicenter Retrospective Study.

INTRODUCTION: We aimed to evaluate the treatment sequence for patients with metastatic castration-resistant prostate cancer (mCRPC) in real-world practice and compare overall survival in each sequential therapy. PATIENTS AND METHODS: We retrospectively evaluated 146 patients with mCRPC who were initially treated with androgen deprivation therapy as metastatic hormone-naive prostate cancer in 14 hospitals between January 2010 and March 2019. The agents for the sequential therapy included new androgen receptor-targeted agents (ART: abiraterone acetate or enzalutamide), docetaxel, and/or cabazitaxel. We evaluated the treatment sequence for mCRPC and the effect of sequence patterns on overall survival. RESULTS: The median age was 71 years. A total of 35 patients received ART-ART, 33 received ART-docetaxel, 68 received docetaxel-ART, and 10 received docetaxel-cabazitaxel sequences. The most prescribed treatment sequence was docetaxel-ART (47%), followed by ART-ART (24%). Overall survival calculated from the initial diagnosis reached 83, 57, 79, and 37 months in the ART-ART, ART-docetaxel, docetaxel-ART, and docetaxel-cabazitaxel, respectively. Multivariate Cox regression analyses showed no significant difference in overall survival between the first-line ART (n = 68) and first-line docetaxel (n = 78) therapies (hazard ratio [HR], 0.84; P = .530), between the ART-ART (n = 35) and docetaxel-mixed (n = 111) sequences (HR, 0.82; P = .650), and between the first-line abiraterone (n = 32) and first-line enzalutamide (n = 36) sequences (HR, 1.58; P = .384). CONCLUSION: The most prescribed treatment sequence was docetaxel followed by ART. No significant difference was observed in overall survival among the treatment sequences in real-world practice.

Clinical Characterization of Low Prostate-specific Antigen on Prognosis in Patients With Metastatic Castration-naive Prostate Cancer.

INTRODUCTION: This study aimed to investigate the effect of low prostate-specific antigen (PSA) on prognosis, as the association of initial PSA level with prognosis in patients with metastatic castration-naive prostate cancer (mCNPC) remains unclear. PATIENTS AND METHODS: We evaluated 575 patients with mCNPC from 10 hospitals. Patients were stratified into 2 groups according to their initial PSA: PSA < 100 and PSA ≥ 100 groups. We compared castration-resistant prostate cancer (CRPC)-free survival, overall survival (OS), and OS from the CRPC diagnosis between the groups. Multivariate Cox regression analysis was performed to evaluate the effect of initial PSA level on prognosis. RESULTS: Of the 575 patients, 196 (34%) patients belonged to the PSA < 100 group. No significant difference was found in patients' backgrounds except for PSA, the extent of disease, and high tumor burden between the groups. CRPC-free survival was significantly shorter in the PSA ≥ 100 group than in the PSA < 100 group. However, the OS after CRPC diagnosis was significantly shorter in the PSA < 100 group than that of the PSA ≥ 100 group. Multivariate analyses showed that PSA < 100 ng/mL was an independent factor for OS after CRPC, whereas no significant association was observed in the CRPC-free survival and OS. CONCLUSIONS: A significant effect of initial PSA < 100 ng/mL on OS after CRPC was observed. PSA < 100 ng/mL might be a poor prognostic factor in patients with mCNPC after CRPC.

Changes in conditional net survival and dynamic prognostic factors in patients with newly diagnosed metastatic prostate cancer initially treated with androgen deprivation therapy.

BACKGROUND: The purpose of this study was to identify predictive factors associated with conditional net survival in patients with metastatic hormone-naive prostate cancer (mHNPC) initially treated with androgen deprivation therapy (ADT). METHODS: At nine hospitals in Tohoku, Japan, the medical records of 605 consecutive patients with mHNPC who initially received ADT were retrospectively reviewed. The Pohar Perme estimator was used to calculate conditional net cancer-specific survival (CSS) and overall survival (OS) for up to 5 years subsequent to the diagnosis. Using multiple imputation, proportional hazard ratios for conditional CSS and OS were calculated with adjusted Cox regression models. RESULTS: During a median follow up of 2.95 years, 208 patients died, of which 169 died due to progressive prostate cancer. At baseline, the 5-year CSS and OS rates were 65.5% and 58.2%, respectively. Conditional 5-year net CSS and OS survival gradually increased for all the patients. In patients given a 5-year survivorship, the conditional 5-year net CSS and OS rates improved to 0.906 and 0.811, respectively. Only the extent of disease score (EOD) ≥2 remained a prognostic factor for CSS and OS up to 5 years; as survival time increased, other variables were no longer independent prognostic factors. CONCLUSIONS: The conditional 5-year net CSS and OS in patients with mHNPC gradually increased; thus, the risk of mortality decreased with increasing survival. The patient's risk profile changed over time. EOD remained an independent prognostic factor for CSS and OS after 5-year follow-up. Conditional net survival can play a role in clinical decision-making, providing intriguing information for cancer survivors.