Clinical characteristics and survival outcomes of elderly patients with de novo metastatic germ cell tumors.

OBJECTIVES: To determine the outcomes for elderly patients with de novo metastatic germ cell tumors and the influence of patient age on adherence to standard chemotherapy. METHODS: A total of 150 patients who were initially diagnosed with metastatic germ cell tumors and treated at our institution between 2007 and 2021 were included. Patients were classified according to three age groups: aged <40, 40-49, and ≥50 years. Clinicopathological features, adherence to standard first-line chemotherapy, overall survival, and disease-free survival were compared between these groups. We also analyzed the outcomes of patients who received low-intensity induction chemotherapy due to adverse events and/or comorbidities. RESULTS: There was no significant difference in any of the survival outcomes and in the rate of adherence to standard first-line chemotherapy between the three age groups, although elderly patients with intermediate/poor prognosis group tended to receive less-intense chemotherapies. The rate of febrile neutropenia as a chemotherapy-related adverse event was significantly higher in patients aged ≥50 years. No statistical significance in survival outcomes was detected between the group of patients who received relatively low-intensity induction chemotherapy and those who received adequately intensive planned chemotherapy. CONCLUSIONS: The adherence rate of standard fist-line chemotherapy of elderly patients is almost comparable to that of younger patients, although some adverse events should be carefully managed. Even elderly patients with metastatic germ cell tumors can aim for equivalently good survival outcome like younger populations, with effort to adhere to standard chemotherapy.

Significant reduction in burden of metastatic disease by intermittent docetaxel therapy in a patient with castration-resistant prostate cancer.

Intermittent docetaxel therapy (IDT) is rarely used nowadays as a treatment option for men with metastatic castration-resistant prostate cancer (mCRPC) because of the widespread availability of androgen receptor axis-targeted therapy, which is less toxic. Therefore, there is limited information available on whether IDT has a clinical benefit in the treatment of men with mCRPC. This report describes the case of a 66-year-old man with a diagnosis of cT2N1M0 prostate cancer who underwent neoadjuvant combined androgen blockade and whole-pelvis radiation therapy. However, the tumor had progressed to mCRPC with metastasis to the bladder and a left pelvic lymph node within 2 years. Docetaxel had been administered as first-line chemotherapy, and the patient achieved a complete response in terms of the bladder metastasis. Docetaxel was stopped after 15 cycles. When a durable response had been maintained for more than 2 years, during which only androgen deprivation therapy was administered, the patient was switched to observation only. However, his prostate-specific antigen level gradually increased. Abiraterone was started as second-line therapy, during which there was a rapid increase in the PSA level. Computed tomography revealed further enlargement of the left pelvic lymph node, bladder metastasis, metastasis to the left common iliac lymph nodes, and several disseminated nodules around the bladder. Docetaxel was reintroduced as IDT for third-line therapy, and a complete response was achieved for all metastases, with the exception of the metastasis in the left pelvic lymph node. Thus far, the patient has survived for more than 7 years after starting docetaxel as first-line therapy for mCRPC. IDT is potentially useful in a subgroup of patients with mCRPC and could achieve long-term survival. Comprehensive genomic profiling may help physicians to select patients with mCRPC who are more likely to benefit from docetaxel than other systemic therapy.

Clinical characteristics and management of primary retroperitoneal sarcoma: A literature review.

Retroperitoneal sarcoma (RPS) is a rare tumor classified into many histological types. It is also often detected only after it has grown to a considerable size and requires extensive resection of the surrounding organs, making it difficult to offer optimal patient-tailored management. Evidence supporting specific treatment modalities for RPS is insufficient, owing to its rarity. The Japanese clinical practice guidelines for RPS were published in December 2021, with the aim of accumulating existing evidence and indicating the optimal practice for RPS. These guidelines provide important clinical questions (CQs) concerning the diagnosis and treatment of RPS. This review, with a particular focus on primary RPS, attempts to introduce clinical problems in the diagnosis and treatment of RPS and to assess those problems along with the CQs in the guidelines. According to these guidelines, although chemotherapy and radiotherapy are expected to have therapeutic effects, the level of evidence to support these treatments is not very high at present. Accordingly, complete resection of the tumor is the first and only option for managing primary RPS. However, as with other tumors, the demand for multidisciplinary treatment for RPS is increasing. These guidelines will undoubtedly represent a milestone in clinical practice in relation to RPS in the future, and further evidence is expected to be accumulated based on the CQs that have been proposed.

Inflammatory Rhabdomyoblastic Tumor: Clinicopathologic and Molecular Analysis of 13 Cases.

Inflammatory rhabdomyoblastic tumors (IRMTs) are newly recognized skeletal muscle tumors with uncertain malignant potential. We investigated 13 IRMTs using clinicopathologic, genetic, and epigenetic methods. The cohort included 7 men and 6 women, aged 23 to 80 years (median, 50 years), of whom 2 had neurofibromatosis type 1. Most tumors occurred in the deep soft tissues of the lower limbs, head/neck, trunk wall, and retroperitoneum/pelvis. Two tumors involved the hypopharyngeal submucosa as polypoid masses. Eight tumors showed conventional histology of predominantly spindled cells with nuclear atypia, low mitotic activity, and massive inflammatory infiltrates. Three tumors showed atypical histology, including uniform epithelioid or plump cells and mitotically active histiocytes. The remaining 2 tumors demonstrated malignant progression to rhabdomyosarcoma; one had additional IRMT histology and the other was a pure sarcoma. All 11 IRMTs without malignant progression exhibited indolent behavior at a median follow-up of 43 months. One of the 2 patients with IRMTs with malignant progression died of lung metastases. All IRMTs were positive for desmin and PAX7, whereas myogenin and MyoD1 were expressed in a subset of cases. Targeted next-generation sequencing identified pathogenic mutations in NF1 (5/8) and TP53 (4/8). All TP53 mutations co-occurred with NF1 mutations. TP53 variant allele frequency was much lower than that of NF1 in 2 cases. These tumors showed geographic (subclonal) strong p53 immunoreactivity, suggesting the secondary emergence of a TP53-mutant clone. DNA methylation-based copy number analysis conducted in 11 tumors revealed characteristic flat patterns with relative gains, including chromosomes 5, 18, 20, 21, and/or 22 in most cases. Widespread loss of heterozygosity with retained biparental copies of these chromosomes was confirmed in 4 tumors analyzed via allele-specific profiling. Based on unsupervised DNA methylation analysis, none of the 11 tumors tested clustered with existing reference entities but formed a coherent group, although its specificity warrants further study.

[A Survey on the Concomitant Use of Drugs with Enzalutamide in Medical Practice-The Effects and Resultant Decrease in Efficacy].

PURPOSE: Enzalutamide is a potent inducer of cytochrome P450 substrates. Hence, it induces major metabolizing enzyme effects in some of the concomitant drugs, raising the possibility of decreased efficacy. We investigated the actual status of drugs for which precautions for co-administration are indicated during concomitant use with enzalutamide. METHODS: We retrospectively investigated the duration of enzalutamide use, concomitant medications, laboratory values, and events using the medical records of patients prescribed enzalutamide for castration-resistant prostate cancer at the National Cancer Center Hospital from May 2014 to May 2017. RESULTS: The median age of the 107 studied patients was 74 years[range: 53-93], median duration of enzalutamide prescriptions was 120 days[range: 14-1,008], and the median number of concomitant medications(components)was 6[range: 0-16]. Sixty nine patients(64%)were taking drugs that could be affected by enzyme induction. The medications listed in the concomitant use section of the package insert were warfarin(3 patients) and omeprazole(2 patients). In this study, 4 patients(except for 1 on warfarin)were taking other drugs that could be affected by enzyme induction. Events considered to possibly reduce their efficacy during concomitant use with enzalutamide were elevated blood pressure and blood clots. CONCLUSIONS: When enzalutamide is used in combination with other drugs, there exists the possibility that the effect of concomitant medications may be weakened by enzyme induction.

Liposarcoma With Hibernoma-like Histology: A Clinicopathologic Study of 16 Cases.

Hibernoma is an uncommon benign tumor of brown fat cells that consistently expresses uncoupling protein 1 (UCP1). Herein, we clinicopathologically characterized 16 liposarcomas, for which histology, at least focally, closely resembled that of hibernoma, including sheets of brown fat-like, finely multivacuolated-to-eosinophilic tumor cells with no or minimal nuclear atypia. The cohort consisted of 4 well-differentiated liposarcomas (WDLSs), 6 dedifferentiated liposarcomas with a concomitant WDLS component, and 6 myxoid liposarcomas (MLSs). For all dedifferentiated liposarcoma cases, hibernoma-like histology was present only in the WDLS component. All tumors presented as large, deep-seated masses. Hibernoma-like histology resembled the pale cell, mixed cell, eosinophilic cell, or spindle cell subtypes of hibernoma, and it was a focal observation, with conventional liposarcoma histology coexisting in all cases. However, a few biopsy samples were predominated by hibernoma-like patterns, and 1 case was initially interpreted as hibernoma. Hibernoma-like components in WDLS immunohistochemically coexpressed MDM2 and CDK4 in most cases and harbored MDM2 amplification in tested cases, whereas half of the cases expressed UCP1. The hibernoma-like components of MLS expressed DDIT3, and DDIT3 rearrangements were present in the tested cases, whereas only negative or equivocal UCP1 expression was observed. In summary, WDLS and MLS focally demonstrate hibernoma-like histology on rare occasions. These elements are neoplastic, and some such areas in WDLS likely represent true brown fat differentiation, as supported by UCP1 expression. This pattern requires recognition to avoid the misdiagnosis as hibernoma, especially in biopsies. A careful search for classic liposarcoma histology and additional work-ups for the MDM2/CDK4 or DDIT3 status will be helpful for an accurate diagnosis.

The clinical significance of perioperative inflammatory index as a prognostic factor for patients with retroperitoneal soft tissue sarcoma.

BACKGROUND: The prognostic factors of retroperitoneal soft tissue sarcoma (STS) have been explored but not yet certain. This study evaluated the prognostic impact of various preoperative clinical parameters and inflammatory indices in primary STS, with a particular focus on the transition of inflammatory index before and after tumor resection in de-differentiated liposarcoma (DD-LPS). METHODS: The clinical data of 113 patients with primary retroperitoneal STS receiving tumor resection were reviewed. Six variables (neutrophils, platelets, C-reactive protein (CRP), lymphocytes, albumin, and hemoglobin) in the blood samples were measured and nine inflammatory indices (neutrophil-lymphocyte ratio (NLR), CRP-lymphocyte ratio (CLR), platelet-lymphocyte ratio (PLR), neutrophil-albumin ratio (NAR), CRP-albumin ratio (CAR), platelet-albumin ratio (PAR), HALP (hemoglobin, albumin, lymphocyte and platelet), prognostic nutrition index (PNI), and modified Glasgow Prognostic Score (mGPS)) were calculated. The prognostic value of the indices was analyzed by univariate and multivariate analyses. RESULTS: Elevated NLR, CLR, PLR, NAR, CAR, PAR, and mGPS were associated with a worse overall survival (p = 0.0124, 0.0011, 0.049, 0.0047, 0.0085, 0.0332, and 0.0086, respectively) in univariate analysis. Multivariate analysis showed that elevated CLR and DD-LPS were associated with poor overall survival (p = 0.0267 and 0.0218, respectively) in all retroperitoneal STS. In DD-LPD, patients with preoperative high CLR, whose postoperative CLR was normalized, demonstrated a favorable survival rate similar to those with preoperative low CLR. CONCLUSIONS: Elevated CLR before surgery as well as DD-LPS were poor prognostic markers for overall survival in primary retroperitoneal STS. Perioperative CLR normalization may be related to a favorable prognosis in DD-LPS.

Cytoreductive robot-assisted prostatectomy for systemic prostate rhabdomyosarcoma presenting as urinary retention.

INTRODUCTION: In adults, rhabdomyosarcoma of the prostate is extremely rare and has an unfavorable prognosis. These patients frequently experience urinary obstruction, and cysto-prostatectomy is a mainstay treatment for localized disease. In contrast, treatment strategies for the primary site for metastatic disease remain controversial. To our knowledge, robot-assisted surgery for the primary tumor has not been reported. CASE PRESENTATION: A 26-year-old man complained of dysuria. Magnetic resonance imaging showed enlarged prostate and computed tomography revealed a pulmonary metastasis. Transurethral resection of the prostate led to the diagnosis of rhabdomyosarcoma. After chemotherapy, robot-assisted prostatectomy was performed to relieve obstructive urinary symptoms. Although disease progression in the metastatic site was observed after the surgery, urinary obstruction did not occur and quality of life was well maintained. CONCLUSION: Robot-assisted prostatectomy may be beneficial both for local disease control and palliation of voiding impairment among selected patients with systemic rhabdomyosarcoma of the prostate.

Identification of novel SSX1 fusions in synovial sarcoma.

Synovial sarcoma is characterized by variable epithelial differentiation and specific SS18-SSX gene fusions. The diagnosis is primarily based on phenotype, but fusion gene detection is increasingly being considered indispensable, with SS18 break-apart fluorescence in situ hybridization (FISH) being favored in many laboratories. However, SS18 FISH assay produces negative or atypical results in a minority of cases, leaving uncertainties in diagnosis and management. Here, we analyzed this challenging subset of SS18 FISH-negative/atypical synovial sarcoma using RNA sequencing and monoclonal antibodies that recognize SS18-SSX and the SSX C-terminus. Among 99 synovial sarcoma cases that were previously subjected to SS18 break-apart FISH, eight cases were reported as negative and three cases were indeterminate, owing to atypical signal patterns. Three of these 11 tumors (two monophasic and one biphasic) harbored novel EWSR1-SSX1 fusions, were negative for SS18-SSX staining, and were positive for SSX C-terminus staining. One monophasic tumor harbored a novel MN1-SSX1 fusion, and showed negative SS18-SSX expression and positive SSX C-terminus staining. Another monophasic tumor carried an SS18L1-SSX1 fusion, and was weakly positive for SS18-SSX, while SMARCB1 expression was reduced. The presence of these novel and/or rare fusions was confirmed using RT-PCR and Sanger sequencing. EWSR1-SSX1 was further validated by EWSR1 FISH assay. The remaining six tumors (five monophasic and one biphasic) showed strong SS18-SSX expression, and RNA sequencing successfully performed in three cases identified canonical SS18-SSX2 fusions. Based on a DNA methylation-based unsupervised clustering, the tumors with EWSR1-SSX1 and SS18L1-SSX1 clustered with synovial sarcoma, while the MN1-SSX1-positive tumor was not co-clustered despite classic histology and immunoprofile. In summary, we discovered novel and rare SSX1 fusions to non-SS18 genes in synovial sarcoma. The expanded genetic landscape carries significant diagnostic implications and advances our understanding of the oncogenic mechanism.

Bacillus Calmette-Guérin-unresponsive non-muscle invasive bladder cancer outcomes in patients without radical cystectomy.

BACKGROUND: Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) is a newly defined subtype that is unlikely to benefit from BCG rechallenge. Radical cystectomy is currently recommended for BCG-unresponsive NMIBC; however, a certain proportion of these patients can be managed with treatments other than that. Herein, we conducted a multicenter retrospective study to analyze the clinical outcomes of BCG-unresponsive NMIBC patients who did not receive radical cystectomy. METHODS: Of the 141 BCG-unresponsive NMIBC patients, 94 (66.7%) received treatment except radical cystectomy. Survival outcomes were calculated from the date of diagnosis using the Kaplan-Meier method and compared using the log-rank test. Prognostic factors were identified using the multivariate Cox regression model. This group was further classified into three groups according to the number of risk factors, and survival outcomes were compared. RESULTS: Multivariate analyses identified low estimated glomerular filtration rate (< 45 ml/min/1.73 m2) and large tumor size (≥ 30 mm) before BCG induction as independent poor prognostic factors for progression-free survival and overall survival, while the latter was also an independent factor for cancer-specific survival. The presence of variant histology was an independent poor prognostic factor for overall survival. The high-risk non-cystectomy group showed a significantly poor prognosis for progression-free survival (hazard ratio: 7.61, 95% confidence interval: 2.11-27.5), cancer-specific survival (10.4, 0.54-70.02), and overall survival (8.28, 1.82-37.7). CONCLUSIONS: Our findings suggest that patients with renal impairment and large tumors should undergo radical cystectomy if the complications and intentions of the patients allow so.

Prognostic implication of staging of seminal vesicle invasion in patients with prostatic adenocarcinoma after prostatectomy.

OBJECTIVES: To evaluate whether the extent of seminal vesicle invasion of prostatic adenocarcinoma can stratify the risk of biochemical recurrence after radical prostatectomy. METHODS: We carried out radical prostatectomy for 1309 patients with prostatic adenocarcinoma between 2006 and 2019; 135 (10.3%) patients had seminal vesicle invasion. After excluding patients with neo-/adjuvant therapy, we reviewed 105 patients. We analyzed the correlation of the extent of seminal vesicle invasion and biochemical recurrence-free survival after prostatectomy and adjusted by various clinicopathological factors in multivariate analyses. Seminal vesicle invasion was stratified into three groups; the proximal part from the base was defined as level 1, followed by level 2 and the distal part as level 3. RESULTS: Among the 105 patients, 30 (29%), 54 (51%) and 21 patients (20%) had seminal vesicle invasion at levels 1, 2 and 3, respectively. Median times to biochemical recurrence were 110, 67 and 12 months in patients with levels 1, 2 and 3, respectively (P = 0.002). The extent of seminal vesicle invasion was the independent risk factor for biochemical recurrence in univariate (level 3 vs 1, P = 0.001; level 3 vs 2, P = 0.015) and multivariate analyses (level 3 vs 1, P = 0.025; level 3 vs 2, P = 0.030). CONCLUSIONS: The extent of seminal vesicle invasion might be a significant predictor of biochemical recurrence in prostate cancer patients undergoing radical prostatectomy.

Patient-reported outcomes following neoadjuvant endocrine therapy, external beam radiation, and adjuvant continuous/intermittent endocrine therapy for locally advanced prostate cancer: A randomized phase III trial.

BACKGROUND: We evaluated patient-reported outcomes (PRO) during neoadjuvant androgen deprivation therapy (ADT) plus external beam radiation therapy (EBRT) followed by either adjuvant continuous ADT (CADT) or intermittent ADT (IADT) for patients with locally advanced prostate cancer (Pca). METHODS: A multicenter, randomized phase III trial enrolled 303 patients with locally advanced Pca. The patients were treated with 6 months (M) of ADT followed by 72 Gy of EBRT, and were randomly assigned to CADT or IADT after 14 M. The PROs were evaluated at sic points: baseline, 6 M, 8 M, 14 M, 20 M, and 38 M using FACT-P questionnaires and EPIC urinary, bowel, and sexual bother subscales. RESULTS: The FACT-P total scores were significantly better (p < 0.05) in IADT versus CADT at 20 M (121.6 vs.115.4) and at 38 M (119.9 vs. 115.2). The physical well-being scores (PWB) were significantly better (p < 0.05) in IADT versus CADT at 38 M (25.4 vs. 24.0). The functional scores were significantly better in IADT than those in CADT at 14 M (20.2 vs18.7, p < 0.05) and at 20 M (21.0 vs.18.9, p < 0.05). CONCLUSION: The PRO was significantly favorable in IADT on FACT-P total score at 20 M and 38 M, PWB and functional scores at 38 M.

Treatment results of radiotherapy to both the prostate and metastatic sites in patients with bone metastatic prostate cancer.

Although systemic therapy is the standard treatment for metastatic prostate cancer, a randomized controlled trial showed radiotherapy to the prostate improved overall survival of metastatic prostate cancer patients with the low metastatic burden. Additionally, a randomized phase II trial showed that metastasis-directed therapy for oligo-recurrent prostate cancer improved androgen-deprivation therapy (ADT)-free survival. Therefore, administering radiotherapy to both prostate and metastatic regions might result in better outcomes. Thus, we report the treatment results of radiotherapy to both prostate and metastatic regions. Our institutional database was searched for patients who received radiotherapy to the prostate and metastatic regions. We summarized patient characteristics and treatment efficacy and performed statistical analysis to find possible prognostic factors. A total of 35 patients were included in this study. The median age was 66 years, and the median initial prostate-specific antigen (PSA) level was 32 ng/ml. The Gleason score was 7 in 10 patients, 8 in 13 patients, and 9 in 12 patients. The median radiotherapy dose was 72 Gy to the prostate and 50 Gy to the metastatic bone region. The 8-year overall survival, cause-specific survival, progression-free survival, and freedom from biochemical failure rate were 81, 85, 53, and 57%. Among the 35 patients, 12 were disease-free even after ADT was discontinued. In selected patients with metastatic prostate cancer, ADT and radiotherapy to the prostate and metastatic sites were effective. Patients with good response to ADT may benefit from radiotherapy to both prostate and metastatic regions.

External validation of the albumin, C-reactive protein and lactate dehydrogenase model in patients with metastatic renal cell carcinoma receiving second-line axitinib therapy in a Japanese multi-center cohort.

PURPOSE: To externally validate the utility of the albumin, C-reactive protein and lactate dehydrogenase model to predict the overall survival of previously treated metastatic renal cell carcinoma patients. PATIENTS AND METHODS: The ability of the albumin, C-reactive protein and lactate dehydrogenase model to predict overall survival was validated and compared with those of other prognostication models using data from 421 metastatic renal cell carcinoma patients receiving second-line axitinib therapy at 36 hospitals belonging to the Japan Urologic Oncology Group. RESULTS: The following factors in this cohort were independently associated with poor overall survival in a multivariate analysis: a low Karnofsky performance status, <1 year from diagnosis to targeted therapy, a high neutrophil count, and low albumin, elevated C-reactive protein, and elevated lactate dehydrogenase, and the Japan Urologic Oncology Group model was newly developed based on the presence/absence of these independent factors. In this cohort, 151 (35.9%), 125 (27.7%) and 145 (34.4%) patients were classified into the favorable, intermediate and poor risk groups, respectively, according to the albumin, C-reactive protein and lactate dehydrogenase model; however, the proportions of patients in the intermediate risk group stratified by the Japan Urologic Oncology Group, Memorial Sloan Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium models were >50%. The superiority of the albumin, C-reactive protein and lactate dehydrogenase model to the Memorial Sloan Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium models, but not the Japan Urologic Oncology Group model, was demonstrated by multiple statistical analyses. CONCLUSIONS: The utility of the albumin, C-reactive protein and lactate dehydrogenase model as a simple and objective prognostication tool was successfully validated using data from 421 metastatic renal cell carcinoma patients receiving second-line axitinib.

The use of hyperbaric oxygen to treat actinic rectal fistula after SpaceOAR use and radiotherapy for prostate cancer: a case report.

BACKGROUND: In definitive radiation therapy for prostate cancer, the SpaceOAR® System, a hydrogel spacer, is widely used to decrease the irradiated dose and toxicity of rectum. On the other hand, periprostatic abscesses formation and rectal perforation are known as rare adverse effects of SpaceOAR. Nevertheless, there is a lack of reports clarifying the association between aggravation of abscesses and radiation therapy, and hyperbaric oxygen therapy (HBOT) is effective for a peri-SpaceOAR abscess and rectal perforation. CASE PRESENTATION: We report a case of a 78-year-old high-risk prostate cancer patient. After SpaceOAR insertion into the correct space, he started to receive external beam radiation therapy (EBRT). He developed a fever, perineal pain and frequent urination after the completion of EBRT, and the magnetic resonance imaging (MRI) revealed a peri-SpaceOAR abscess. Scheduled brachytherapy was postponed, administration of antibiotics and opioid via intravenous drip was commenced, and transperineal drainage was performed. After the alleviation of the abscess, additional EBRT instead of brachytherapy was performed with MRI-guided radiation therapy (MRgRT). On the last day of the MRgRT, perineal pain reoccurred, and MRI and colonoscopy detected the rectal perforation. He received an intravenous antibiotics drip and HBOT, and fully recovered from the rectal perforation. CONCLUSIONS: Our report indicates that EBRT can lead to a severe rectum complication by causing inflammation for patients with a peri-SpaceOAR abscess. Furthermore, HBOT was effective for the peri-SpaceOAR abscess and rectal perforation associated with EBRT.

Clinical outcomes of definitive whole pelvic radiotherapy for clinical lymph node metastatic prostate cancer.

BACKGROUND: In this study, we aim to present the clinical outcomes of radiotherapy (RT) in clinical pelvic lymph node-positive prostate cancer (cN1) patients. We also analyze the prognostic factors with focus on RT dose escalation to metastatic lymph nodes (LN). METHODS: We retrospectively analyzed the data from cN1 patients who were treated with definitive RT and androgen deprivation therapy (ADT) between June 2004 and February 2016. All patients received localized irradiation to the prostate region and whole pelvis irradiation. Some patients received intensity-modulated radiation therapy with RT dose escalation to metastatic LN. Univariate analyses using log-rank test were performed to find prognostic factors between patient subgroups. RESULTS: Fifty-one consecutive patients were identified. The median follow-up period for all patients was 88 (range 20-157) months. Primary Gleason pattern and LN RT dose were statistically significant prognostic factors for relapse-free survival (RFS) and distant metastasis-free survival (DMFS). Especially, RT dose escalation (60 Gy or more) to metastatic LN significantly improved RFS and DMFS compared with standard dose RT (4-year RFS 90.6% vs 82.1%, 7-year RFS 90.6% vs 58.0%, P = .015; 4-year DMFS 90.6% vs 82.1%, 7-year DMFS 90.6% vs 62.8%, P = .023). The following factors were all statistically significant for biochemical relapse-free survival (BRFS): T stage, LN RT dose, local RT dose, and ADT duration period. Any significantly different toxicity was not seen for each LN or local RT dose except for the incident rate of grade 2 or more acute urinary retention, which was significantly higher in the higher LN RT dose (60 Gy or more) group by the Chi-square test. CONCLUSIONS: RT dose escalation to metastatic LN in cN1 patients improves BRFS, RFS, and DMFS at 4 and 7 years, without increasing severe adverse events.

Oncological outcomes for patients with locally advanced prostate cancer treated with neoadjuvant endocrine and external-beam radiation therapy followed by adjuvant continuous/intermittent endocrine therapy in an open-label, randomized, phase 3 trial.

BACKGROUND: To date, research has not determined the optimal procedure for adjuvant androgen deprivation therapy (ADT) in patients with locally advanced prostate cancer (PCa) treated for 6 months with neoadjuvant ADT and external-beam radiation therapy (EBRT). METHODS: A multicenter, randomized, phase 3 trial enrolled 303 patients with locally advanced PCa between 2001 and 2006. Participants were treated with neoadjuvant ADT for 6 months. Then, 280 patients whose prostate-specific antigen levels were less than pretreatment levels and less than 10 ng/mL were randomized. All 280 participants were treated with 72 Gy of EBRT in combination with adjuvant ADT for 8 months. Thereafter, participants were assigned to long-term ADT (5 years in all; arm 1) or intermittent ADT (arm 2). The primary endpoint was modified biochemical relapse-free survival (bRFS) with respect to nonmetastatic castration-resistant prostate cancer (nmCRPC) progression, clinical relapse, or any cause of death. RESULTS: The median follow-up time after randomization was 8.2 years. Among the 136 and 144 men assigned to trial arms 1 and 2, respectively, 24 and 30 progressed to nmCRPC or clinical relapse, and 5 and 6 died of PCa. The 5-year modified bRFS rates were 84.8% and 82.8% in trial arms 1 and 2, respectively (hazard ratio, 1.132; 95% confidence interval, 0.744-1.722). CONCLUSIONS: Although modified bRFS data did not demonstrate noninferiority for arm 2, intermittent adjuvant ADT after EBRT with 14 months of neoadjuvant and short-term adjuvant ADT is a promising treatment strategy, especially in a population of responders after 6 months of ADT for locally advanced PCa.

Oncological outcomes of a multicenter cohort treated with axitinib for metastatic renal cell carcinoma.

The present study aimed to evaluate the efficacy of the real-world use of axitinib and to develop a prognostic model for stratifying patients who could derive long-term benefit from axitinib. This was a retrospective, descriptive study evaluating the efficacy of axitinib in patients with metastatic renal cell carcinoma that had been treated with 1 or 2 systemic antiangiogenic therapy regimens at 1 of 36 hospitals belonging to the Japan Urologic Oncology Group between January 2012 and February 2019. The primary outcome was overall survival (OS). Using a split-sample method, candidate variables that exhibited significant relationships with OS were chosen to create a model. The new model was validated using the rest of the cohort. In total, 485 patients were enrolled. The median OS was 34 months in the entire study population, whereas it was not reached, 27 months, and 14 months in the favorable, intermediate, and poor risk groups, respectively, according to the new risk classification model. The following 4 variables were included in the final risk model: the disease stage at diagnosis, number of metastatic sites at the start of axitinib therapy, serum albumin level, and neutrophil : lymphocyte ratio. The adjusted area under the curve values of the new model at 12, 36, and 60 months were 0.77, 0.82, and 0.82, respectively. The efficacy of axitinib in routine practice is comparable or even superior to that reported previously. The patients in the new model's favorable risk group might derive a long-term survival benefit from axitinib treatment.

Publisher Correction: Integrated exome and RNA sequencing of dedifferentiated liposarcoma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Expanding the clinicopathologic and molecular spectrum of BCOR-associated sarcomas in adults.

AIMS: BCOR gene alteration is a genetic signature of rare subsets of sarcomas. Most BCOR-associated sarcomas thus far reported are in the pediatric population, except for uterine sarcomas. We studied seven cases of BCOR-associated non-uterine sarcomas in adult patients. METHODS AND RESULTS: The patients were four men and three women ranging from 26 to 71 years in age. Three tumors, two of which primarily affected the kidney, showed BCOR-CCNB3. One tumor with a ZC3H7B-BCOR occurred in the chest wall, and a tumor with a novel CIITA-BCOR was found in the sinonasal tract. Two tumors in the lung and breast harbored exon 15 internal tandem duplications of BCOR, a highly unexpected observation in this age group. All seven sarcomas consisted of dense proliferations of uniform round to spindle cells with fine chromatin within vascular stroma. BCOR-CCNB3 sarcomas showed swirling fascicular growth. The tumor with the ZC3H7B-BCOR fusion showed a multinodular growth of spindle cells, and the tumors with the CIITA-BCOR fusion showed palisading of oval cells. Both tumors with BCOR internal tandem duplication demonstrated nested to palisading growth of round cells within sclerotic non-myxoid stroma. All seven sarcomas diffusely expressed BCOR and SATB2 immunohistochemically, with all three BCOR-CCNB3 sarcomas being immunopositive for CCNB3. BCOR alterations were confirmed by RNA sequencing, polymerase chain reaction, Sanger sequencing, and/or fluorescence in situ hybridization. CONCLUSIONS: This study expands the clinicopathologic and molecular spectrum of BCOR-associated sarcomas, and emphasizes the importance of being aware of this entity in the differential diagnosis of adult non-uterine sarcomas.