Improved survival of poor-risk non-seminomatous germ cell tumor patients: real-world data from a single institute in Japan.

OBJECTIVES: The International Germ Cell Cancer Collaborative Group Update Consortium showed the improved survival of patients with a non-seminomatous germ cell tumor. We updated the survival data of the non-seminomatous germ cell tumor patients treated at our hospital. PATIENTS AND METHODS: We analyzed the outcomes of 138 patients treated in 1981-2018. We compared the survival of the patients treated in the early (1981-99) and later (2000-18) periods and determined the groups' progression-free survival and overall survival using the Kaplan-Meier method. We used a web-based application of the International Germ Cell Cancer Collaborative Group Update model to calculate each patient's predicted 3-year progression-free survival. RESULTS: The 5-year progression-free survival rates of the good, intermediate and poor prognosis groups were 91, 83 and 64%, and their 5-year overall survival rates were 97, 89 and 82%, respectively. There were no significant differences in the progression-free survival or overall survival of the good and intermediate prognosis groups by treatment year. The 5-year progression-free survival of the poor prognosis group was almost identical in both treatment year (60 and 65%, respectively). By contrast, the 5-year overall survival in the later period (85%) was higher than that in the early period (70%). The median-predicted 3-year progression-free survival rates of the good, intermediate and poor prognosis groups were 92, 83 and 51% (P < 0.01), respectively. The concordance index for the good, intermediate and poor prognosis groups were 0.56, 0.79 and 0.67, respectively. CONCLUSION: The survival of our poor prognosis non-seminomatous germ cell tumor patients improved over time. The 5-year overall survival of patients treated in 2000-18 reached 85%.

Plasma circulating tumor DNA profiling in patients with chemo-refractory germ cell tumors.

OBJECTIVES: Molecular analysis of tumor tissues has been extensively analyzed in germ cell tumors. However, genetic analysis of plasma circulating tumor DNA has been limited. Our objective was to analyze genetic alterations in circulating tumor DNA as well as its impact on prognosis in patients with chemo-refractory germ cell tumors. METHODS: We included 13 patients with chemo-refractory germ cell tumors who relapsed after second-line or higher previous chemotherapy and performed targeted sequencing of plasma cell-free DNA using an AVENIO Expanded kit. RESULTS: Tumor-specific genetic alterations were identified in all patients. The most frequently mutated gene was TP53 (53.4%), followed by PTEN (23.1%), GNAS (15.4%) and MTOR (15.4%). Moreover, EGFR amplification (38.5%) and MET amplification (15.4%) were also identified. We defined two or more single nucleotide variants detected in plasma cell-free DNA as circulating tumor DNA-positive. Kaplan-Meier analysis revealed that overall survival was significantly shorter in circulating tumor DNA-positive patients than circulating tumor DNA negative-patients (median overall survival 3.13 vs. 8.73 months; p = 0.042). CONCLUSION: Analysis of plasma circulating tumor DNA could detect genetic alterations in patients with chemo-refractory GCT. Moreover, detectable circulating tumor DNA in plasma was associated with poor prognosis in those patients. These results suggest that liquid biopsy using analysis of plasma circulating tumor DNA may be clinically useful for germ cell tumor patients.

Sexual function using the EORTC QLQ-TC26 in testicular cancer survivors: A multi-institutional, cross-sectional study.

OBJECTIVE: To evaluate sexual function after treatment using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 (EORTC QLQ-TC26) questionnaire in Japanese testicular cancer (TC) survivors in a multi-institutional, cross-sectional study. METHODS: This study enrolled TC survivors who visited any of eight high-volume institutions in Japan from 2018 to 2019. After obtaining informed consent, participants completed the EORTC QLQ-TC26 questionnaires. We evaluated sexual function after treatment for TC using the EORTC QLQ-TC26 and analyzed the impact of treatment on sexual function in TC survivors. RESULTS: A total of 567 TC survivors responded to the EORTC QLQ-TC26. Median age at the time of response was 43 years (interquartile range [IQR] 35-51 years), and median follow-up period after treatment was 5.2 years (IQR 2.2-10.0 years). Sexual function, particularly ejaculatory function, was significantly lower after post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) than after Surveillance or Chemotherapy groups (p < 0.05). In the PC-RPLND group, nerve-sparing procedure preserved postoperative ejaculatory function after RPLND compared with the non-nerve-sparing and offered improved ejaculatory function with time. On multivariate analysis, RPLND was a significant predictor of post-treatment ejaculatory dysfunction, particularly without nerve-sparing (odds ratio 3.0, 95% CI 1.2-7.7, p < 0.05). In addition, TC survivors with nerve-sparing RPLND had higher sexual activity than those without. CONCLUSION: This survey of the EORTC QLQ-TC26 showed that sexual function and activity in TC survivors after RPLND was reduced in the absence of nerve-sparing techniques.

[A Case of Germ Cell Tumor in which Necrotic Tissue Revealed hCG-Positive in Surgical Specimen of Post-Chemotherapy Retroperitoneal Lymph Node Dissection].

The patient was a 27-year-old male. In December 2020, he was diagnosed with a primary extragonadal germ cell tumor of the retroperitoneum with inferior vena caval (IVC) involvement. After 3 courses of bleomycin, etoposide and cisplatinum and 3 courses of paclitaxel, ifosfamide and cisplatin, the serum human chorionic gonadotropin (hCG) level remained abnormally low. He was referred to our department after follow-up for 2 months. Since the hCG level continued to decrease during follow-up, we decided to perform marker-positive surgery. He underwent retroperitoneal lymph node dissection. We also resected a part of the IVC wall and tumor in the IVC. The serum hCG level was normalized at 5 days after surgery. Pathological examination revealed only necrotic tissue. Immunohistochemistry showed hCG positive in the necrotic tissue.

Japan Society of Clinical Oncology Clinical Practice Guidelines 2017 for fertility preservation in childhood, adolescent, and young adult cancer patients: part 2.

The Japan Society of Clinical Oncology (JSCO) published the "JSCO Clinical Practice Guidelines 2017 for Fertility Preservation in Childhood, Adolescent, and Young Adult Cancer Patients" in 2017. This was the first guideline in cancer reproductive medicine in Japan. In the field of cancer reproductive medicine, close cooperation between an oncologist and a physician for reproductive medicine is important from before treatment initiation until long after treatment. The guideline takes into consideration disease specificity and provides opinions from the perspective of oncologists and specialists in reproductive medicine that are in line with the current state of the Japanese medical system. It is intended to serve as a reference for medical staff in both fields regarding the availability of fertility preservation therapy before the start of cancer treatment. Appropriate use of this guideline makes it easier to determine whether fertility preservation therapy is feasible and, ultimately, to improve survivorship in childhood, adolescent, and young adult cancer patients. In this article (Part 2), we describe details by organ/system and also for pediatric cancer.

Japan Society of Clinical Oncology Clinical Practice Guidelines 2017 for fertility preservation in childhood, adolescent, and young adult cancer patients: part 1.

In 2017, the Japan Society of Clinical Oncology (JSCO) published the JSCO Clinical Practice Guidelines 2017 for Fertility Preservation in Childhood, Adolescent, and Young Adult Cancer Patients. These were the first Japanese guidelines to address issues of oncofertility. In this field of medicine, sustained close cooperation between oncologists and reproductive specialists is essential from the diagnosis of cancer until many years after completion of cancer treatment. These JSCO guidelines were intended to guide multidisciplinary medical staff in considering the availability of fertility preservation options and to help them decide whether to provide fertility preservation to childhood, adolescent, and young adult cancer patients before treatment starts, with the ultimate goal of improving patient survivorship. The guidelines are presented as Parts 1 and 2. This article (Part 1) summarizes the goals of the guidelines and the methods used to develop them and provides an overview of fertility preservation across all oncology areas. It includes general remarks on the basic concepts surrounding fertility preservation and explanations of the impacts of cancer treatment on gonadal function by sex and treatment modality and of the options for protecting/preserving gonadal function and makes recommendations based on 4 clinical questions. Part 2 of these guidelines provides specific recommendations on fertility preservation in 8 types of cancer (gynecologic, breast, urologic, pediatric, hematologic, bone and soft tissue, brain, and digestive).

A Case of a Solitary Cortical Tuber with No Other Manifestations of Tuberous Sclerosis Complex Mimicking Focal Cortical Dysplasia Type II with Calcification.

Cortical tubers are one of the typical intracranial manifestations of tuberous sclerosis complex (TSC). Multiple cortical tubers are easy to diagnose as TSC; however, a solitary cortical tuber without any other cutaneous or visceral organ manifestations can be confused with other conditions, particularly focal cortical dysplasia. We report a surgical case of refractory epilepsy caused by a solitary cortical tuber mimicking focal cortical dysplasia type II, and describe the radiological, electrophysiological, and histopathological findings of our case.

Phase II trial of nivolumab monotherapy and biomarker screening in patients with chemo-refractory germ cell tumors.

OBJECTIVES: Germ cell tumors are highly susceptible to chemotherapy; however, there is a lack of established treatments for consistently relapsing germ cell tumor. Therefore, in this phase II study, we evaluated the efficacy and safety of nivolumab for relapsed germ cell tumor. METHODS: Seventeen adult patients (median age 34 years) with refractory primary germ cell tumor after second-line or higher chemotherapy were enrolled. Nivolumab was administered over 30 min at 240 mg/body every 2 weeks until disease progression or intolerable adverse event occurrence. The primary endpoint was the overall response rate. RESULT: We performed a biomarker analysis of programmed death ligand-1 expression and genomic sequencing. Tumor histology revealed nonseminoma and seminoma in 14 and three patients, respectively. Patients were pretreated with a median of three chemotherapy lines, and three patients received high-dose chemotherapy. The median number of nivolumab doses was 3 (range 2-46). One patient showed a partial response and three showed stable disease. Responses were durable in one patient with a partial response and one patient with stable disease (median 90 and 68 weeks, respectively). Nivolumab was well-tolerated, with only two Grade 3 adverse events observed. Programmed death ligand-1 expression was not associated with objective responses. Genomic sequencing revealed a high tumor mutation burden in a patient with a durable partial response. While a small subset of chemorefractory germ cell tumors may respond to nivolumab, programmed death ligand-1 is unreliable to measure response. CONCLUSIONS: Tumor mutation burden is a potential biomarker for future testing of germ cell tumor response.

Association of financial toxicity with quality of life in testicular cancer survivors.

OBJECTIVES: Most testicular cancer (TC) survivors have long-term survival. However, the association between financial toxicity (FT), which is an economic side effect of cancer treatment, and the quality of life (QOL) of TC survivors is still unclear. Thus, the impact of FT on the QOL of TC survivors was examined in a multi-institutional cross-sectional study. METHODS: We recruited TC survivors from eight high-volume institutions in Japan between January 2018 and March 2019. A total of 562 participants completed the EORTC QLQ-C30, EORTC QLQ-TC26 and the questionnaires on demographics, including annual income. Financial difficulty in the EORTC QLQ-C30 and low income were used to assess financial distress (FD) and financial burden (FB), respectively. FT was defined as FD and FB. The QOL scores were compared, and a multivariate logistic regression analysis for FT was performed. RESULTS: With severe FD, TC survivors had more treatment side effects, physical limitations, and anxiety concerning employment and future. The TC survivors who reported low income were worried about their jobs and the future. The QOL of the survivors with FT exhibited high impairment, except for sexual activity. In particular, the TC survivors with FT were physically limited and anxious concerning the future. The multivariate logistic regression analysis revealed that four or more chemotherapy cycles were substantial risk factors for FT (4 cycles, odds ratio (OR) = 4.17; ≥5 cycles, OR = 6.96). CONCLUSIONS: TC survivors who received multi-cycle chemotherapy were prone to experience FT, resulting in a decline in their health-related QOL.

Advanced germ cell tumor patients undergoing post-chemotherapy retroperitoneal lymph node dissection: Impact of residual teratoma on prognosis.

OBJECTIVES: To evaluate the histologic findings and clinical outcomes of post-chemotherapy retroperitoneal lymph node dissection for advanced germ cell tumor. METHODS: We analyzed the medical records of 66 patients who underwent post-chemotherapy retroperitoneal lymph node dissection between 2005 and 2019 at Tsukuba University Hospital. RESULTS: The proportions of necrosis, teratoma, and viable germ cell tumor in the specimens were 62.1%, 36.4%, and 1.5%, respectively. The 5-year progression-free and overall survival rates were 82.3% and 91.3%, respectively. The 5-year overall survival rate of patients with residual teratoma was significantly worse than that of patients with necrosis only (74.1% vs 100%). Overall, three patients died: one from cancer and two from teratoma with somatic-type malignancy. Of these, two patients relapsed after incomplete resection of residual teratoma. When limited to patients with completely resected teratoma, the 5-year overall survival rate was 91.7%, which did not differ from that for patients with necrosis only. Multivariate analysis showed that presence of teratoma in the primary site and decrease in retroperitoneal lymph node mass to less than 50% of the initial tumor size were independent factors for residual teratoma. However, the absence of these factors could not reliably predict necrosis only in retroperitoneal lymph node dissection specimens. CONCLUSIONS: In our series, 98% of post-chemotherapy retroperitoneal lymph node dissection pathology was either necrosis or teratoma, with viable germ cell tumor only found in 2% of patients. Residual teratoma was associated with poorer prognosis, especially in cases of incomplete resection.

Prognostic impact of non-urothelial carcinoma of the upper urinary tract: Analysis of hospital-based cancer registry data in Japan.

OBJECTIVES: To identify the prognosis of patients with non-urothelial carcinoma of the upper urinary tract and compare it with that of patients with urothelial carcinoma. METHODS: We used hospital-based cancer registry data in Japan to extract histologically confirmed non-urothelial carcinoma and urothelial carcinoma cases of the upper urinary tract diagnosed in 2008-2009. We estimated the 5-year overall survival by a Kaplan-Meier analysis. The Cox proportional hazards regression analysis was used to evaluate prognostic factors. RESULTS: A total of 2567 upper urinary tract cancer patients with confirmed histological subtypes were identified. The most common histology of non-urothelial carcinoma was squamous cell carcinoma (n = 88, 3.4%) followed by adenocarcinoma (n = 33, 1.3%) and small cell carcinoma (n = 10, 0.4%). The proportion of advanced stage in the squamous cell carcinoma patients was significantly higher than that in the urothelial carcinoma patients (P = 0.003). In stage IV, the proportion of patients who received a combination of surgery + chemotherapy in the urothelial carcinoma group was higher than that in the non-urothelial carcinoma group (34% vs 16%, respectively). The 5-year overall survival rates of the non-urothelial carcinoma patients at stages I-III and stage IV were significantly worse than those of the urothelial carcinoma patients (P = 0.003, P < 0.001, respectively). In multivariate analyses, age ≥73 years, advanced stage (stage IV), tumor location (ureter) and the presence of non-urothelial carcinoma histology were independent poor prognosis factors. CONCLUSION: The prognosis of non-urothelial carcinoma patients is worse than that of urothelial carcinoma patients, especially for non-urothelial carcinoma patients at stage IV. More effective systemic therapies are required to improve these patients' oncological outcomes.

Fertility and reproductive technology use in testicular cancer survivors in Japan: A multi-institutional, cross-sectional study.

OBJECTIVE: To evaluate fertility and use of reproductive technology of testicular cancer survivors in a multi-institutional, cross-sectional study. METHODS: This study recruited testicular cancer survivors who were followed after treatment for testicular cancer at eight high-volume institutions between 2018 and 2019. The participants completed the questionnaires on marital status, fertility and use of reproductive technology. RESULTS: A total of 567 testicular cancer survivors, with a median age of 43 years, responded to the questionnaire. Chemotherapy was given to 398 survivors, including three cycles of cisplatin-based chemotherapy in 106 patients and four cycles in 147 patients. Among 153 survivors who attempted sperm cryopreservation, 133 (87%) could preserve sperm. Of the 28 survivors whose cryopreserved sperm was used, 17 (61%) fathered children. Of the 72 survivors who fathered children without the use of cryopreserved sperm, 59 (82%) fathered naturally. Whereas 33 (20%) of 169 survivors treated without chemotherapy fathered children without using cryopreserved sperm, 39 (10%) of 398 treated with chemotherapy fathered children (P < 0.05). Furthermore, the paternity rate was 12% and 5% in testicular cancer survivors with three and four cycles of cisplatin-based chemotherapy, respectively (P < 0.05). However, of 121 survivors who wanted to have children, 14 (12%) received counseling about infertility treatment. CONCLUSIONS: Testicular cancer survivors preserving their sperm have a higher paternity rate after chemotherapy, especially after four cycles, than those not using cryopreserved sperm. Physicians who give chemotherapy for testicular cancer need to take particular care not only with respect to recurrence of testicular cancer, but also to post-treatment fertility.

Validation study of the Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 for patients with testicular cancer.

OBJECTIVE: To validate the Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 in Japanese-speaking testicular cancer survivors. METHODS: A total of 200 testicular cancer survivors were recruited at eight high-volume institutions in Japan. The participants completed the Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 and the International Index of Erectile Function 15 questionnaires. A total of 40 participants completed a retest of the questionnaires 2 weeks after the first response. The psychometric properties of the Japanese version including test-retest reliability, internal consistency and concurrent validity were evaluated. RESULTS: The mean age at response was 43 years (range 22-74 years), and the mean period after treatment was 77 months (range 0-416 months). The response rate for each item, except sexual function, was high, and the percentage of missing values was less than 3.5%. For test-retest reliability, seven of 12 scales met the criteria (intraclass correlation 0.70-0.86). For internal consistency, four of seven scales met the criteria (Cronbach's alpha 0.62-0.91). For concurrent validity, treatment side effects of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 were related to some domains of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. The sex-related subscales of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 were moderately correlated with some International Index of Erectile Function 15 domains. CONCLUSIONS: The psychometric properties of the Japanese version are equivalent to the properties of the original European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26. The Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 questionnaire is a useful tool to assess the health-related quality of life of testicular cancer patients.

[A Case of Perfusion Failure of Peritoneal Dialysis Catheter Treated by Reduced Port Surgery].

A 17-year-old man received continuous ambulatory peritoneal dialysis (CAPD) catheter implantation and had started peritoneal dialysis. Perfusion failure of peritoneal dialysis catheter occurred one month after the catheter implantation. Transcatheter contrast examination revealed catheter obstruction about 4-5 cm from the catheter tip. We performed reduced port surgery to remove the obstruction. Laparoscopy revealed that the omentum was adhered to the abdominal wall and wrapped the catheter. We diagnosed the cause of catheter malfunction as omentum wrapping. We removed the omentum from the catheter, and repositioned the catheter into the Douglas fossa. Although CAPD worked successfully after the operation, perfusion failure recurred one month after the operation. The patient requested discontinuation of CAPD and change to hemodialysis. Therefore, we removed the CAPD catheter. The catheter was adhered to the omentum. Reduced port surgery for peritoneal dialysis catheter obstruction has the advantage of being minimally invasive and is a reliable procedure, but further studies are needed to reduce the recurrence rate of perfusion failure and to establish the procedure after perfusion failure.

Predictors of venous thromboembolism development before and during chemotherapy for advanced germ cell tumor.

OBJECTIVE: We retrospectively analyzed the incidence and localization of venous thromboembolism in patients undergoing chemotherapy for advanced germ cell tumor and separately evaluated the risk factors for venous thromboembolism development before and during chemotherapy. METHODS: We included 121 patients treated with cisplatin-based chemotherapy between 2005 and 2018. Venous thromboembolism was defined as venous thrombosis diagnosed using radiological imaging with or without thromboembolic symptoms. We analyzed the clinical parameters for identifying the possible venous thromboembolism risk factors. Khorana score was used to calculate the venous thromboembolism risk. RESULTS: Thirteen patients showed prechemotherapy venous thromboembolism and 13 developed venous thromboembolism during chemotherapy. The most common venous thromboembolism was deep vein thrombosis (10 patients), followed by inferior vena cava thrombus (eight patients) and pulmonary thrombus (six patients). Compared to the group without venous thromboembolism, the group with prechemotherapy venous thromboembolism showed higher proportion of patients with tumors originating in the right testis (10 out of 13), significantly higher lactate dehydrogenase levels (828 IU/L versus 436 IU/L, P = 0.013), significantly higher proportion of patients with retroperitoneal lymph node (RPLN) metastases >5 cm in diameter (76.9% versus 33.7%, P = 0.003) and slightly higher proportion of patients with high-risk Khorana score (≥ 3; 30.8% versus 11.6%). No significant differences were observed between the clinical characteristics of patients with venous thromboembolism developed during chemotherapy and patients without venous thromboembolism. CONCLUSIONS: We show that both RPLN mass > 5 cm and high lactate dehydrogenase levels are significant risk factors for prechemotherapy venous thromboembolism but not for venous thromboembolism development during chemotherapy.

Prognostic significance of non-urothelial carcinoma of bladder: analysis of nationwide hospital-based cancer registry data in Japan.

OBJECTIVES: To identify the prognosis of pure non-urothelial carcinoma (non-UC) of bladder and to compare them with those of pure urothelial carcinoma (UC). METHODS: We used Japan's nationwide hospital-based cancer registry data to extract histologically confirmed pure non-UC and UC cases of bladder diagnosed in 2008-2009. We estimated the 5-year overall survival (OS) by a Kaplan-Meier analysis. RESULTS: A total of 8094 patients with confirmed histological subtypes of bladder cancer were identified. The most common pure non-UC was squamous cell carcinoma (SQ, n = 192, 2.4%) followed by adenocarcinoma (AC, n = 138, 1.7%) and small cell neuroendocrine carcinoma (SmC, n = 54, 0.7%). The proportion of female patients (48%) was significantly higher in the SQ group compared with the pure UC group (P < 0.001). The 5-year OS rate of the non-UC patients was significantly worse than that of the UC patients (40 vs. 61%, P < 0.001). According to stages, the 5-year OS rates of the stage I and III non-UC patients were significantly worse than those of the UC patients (P = 0.001). Considering histologic subtypes and stages, the 5-year OS rates of the stage I SQ patients were worse than those of the AC and SmC patients (46, 68 and 64%, respectively). CONCLUSION: The prognosis of pure non-UC was worse than that of pure UC, especially in the stage I and III non-UC patients. To improve these patients' oncologic outcomes, a more aggressive surgical approach may be necessary in stage I patients with non-UC, especially in pure SQ.

Recent malignant testicular tumor trend in Japan, a country with an aging population: a large-scale study of 2012-2015 hospital-based cancer registry data.

OBJECTIVE: Japan's national database of hospital-based cancer registries is estimated to cover ~67% of all new cancer cases. Using this database, we analyzed the characteristics of the recently diagnosed testicular malignancy. METHODS: We obtained data for 6510 adult testicular malignancy patients diagnosed in 2012-2015. The distributions of patient ages, histological diagnoses and testicular germ cell tumor hospital care volumes were determined. RESULTS: The most common histology was seminoma (60.3% of all testicular malignancies), followed by non-seminoma (24.1%) and diffuse large B-cell lymphoma (13.1%). The median and mean ages of the testicular germ cell tumor patients were high at 38 and 39.8 years, respectively. The age distribution peaked at 30-40 years, followed by 40-50 years. Approximately 18% of testicular germ cell tumor patients were ≥50 years. The ages of the diffuse large B-cell lymphoma patients peaked at 70-80 years (mean 67.7 years). When the analysis was limited to the testicular germ cell tumor patients who received first-course cancer treatment at the participating hospitals, the number of high-volume hospitals with ≥20 testicular germ cell tumor care volume was limited to 61 (10.0% of the 605 hospitals that treated ≥1 testicular germ cell tumor patient). However, when the patients who changed hospitals during treatment or relapsed after treatment completion were analyzed together, the number of high-volume hospitals increased to 104 (17.0% of 612 hospitals). CONCLUSION: The testicular germ cell tumor patients' mean age was nearly 40 years. The proportions of older testicular germ cell tumor patients and diffuse large B-cell lymphoma patients were higher than previously thought. The reasons for this trend are unknown, but it is important to address the trend identified herein in a country with a super-aging population.

Impact of centralization in primary retroperitoneal sarcoma treatment: analysis using hospital-based cancer registry data in Japan.

BACKGROUND: To elucidate the clinicopathological features, hospital-based care volume and prognoses associated with primary retroperitoneal sarcoma (PRS). METHODS: Clinical data on PRS cases, diagnosed from 2008 to 2009 (cohort A) and from 2012 to 2015 (cohort B), were obtained from the national hospital-based cancer registry in Japan. Since data on survival, 5 years after PRS diagnosis, were available only for cohort A, patient prognoses were analyzed in this group alone. RESULTS: The numbers of participating hospitals were 154 in cohort A and 537 in cohort B. In total, 380 and 2011 patients with PRS were identified in cohorts A and B, respectively. The incidence of PRS among all the registered urogenital malignancies was 0.52% (2391/462,866). Liposarcoma was the most commonly observed PRS subtype (55.8%), followed by leiomyosarcoma (19.0%). In cohort A, the 5-year overall survival (OS) was 40.4%. The 5-year OS associated with stage I (n = 107), stages II and III (n = 61), and stage IV (n = 59) disease were 59%, 39%, and 6%, respectively. Only two institutions treated over ten patients per year in each cohort. When institutions were divided by hospital care volume (8 hospitals with ≥ = 3 cases and 149 with < 3 cases/year), there were any statistic differences in the OS. CONCLUSIONS: We presented the distribution and prognoses associated with PRS using a real-world large cohort database. Centralization for PRS management was not established in Japan, while the prognosis did not significantly depend on the treatment volume of hospitals.

A single-institute experience of trimodal bladder-preserving therapy for histologic variants of urothelial carcinoma.

BACKGROUND: We retrospectively evaluated the clinical outcomes of patients with histologic variants of muscle invasive bladder cancer (MIBC) treated with trimodal bladder-preserving therapy (TMT). METHODS: Among 148 patients with clinical T2-3N0M0 MIBC treated with TMT at Tsukuba University Hospital from 1990 to 2015, 11 patients (7.4%) had pathological components of variant urothelial carcinoma (UC). The complete response (CR), overall survival (OS), cause-specific survival (CSS) and progression-free survival (PFS) rates were analyzed in these 11 patients. RESULTS: Among the 11 patients with variant UC, 7 (64%) had UC with squamous and/or glandular differentiation and 4 (36%) had sarcomatoid (n = 1), plasmacytoid (n = 1), signet ring cell (n = 1), or clear cell variant (n = 1). Median follow-up was 49.0 months. Nine (82%) out of 11 patients achieved CR and 2 (22%) out of the 9 developed recurrence. Among seven patients who had UC with squamous and/or glandular differentiation, two developed recurrence and one died of disease. In contrast, 2 (50%) out of four patients with other variants, which were sarcomatoid variant or signet ring cell, developed recurrence and died of disease. Overall, the 5-year OS, CSS, and PFS rates of variant UC were 75%, 75%, and 58%, respectively. CONCLUSIONS: TMT might provide acceptable clinical outcomes for well-selected MIBC patients with histologic variants, especially for those with squamous and/or glandular differentiation. However, we need to pay special attention to other variants such as sarcomatoid variant or signet ring cell. TMT might be an alternative treatment option for patients with histologic variants, although further experiments will be needed to confirm this.

Risk for intravesical recurrence of bladder cancer stratified by the results on two consecutive UroVysion fluorescence in situ hybridization tests: a prospective follow-up study in Japan.

BACKGROUND: A previous comparative study in Japan has demonstrated that the two consecutive UroVysion tests are useful tools to detect the presence of bladder cancer during follow-up after transurethral resection, but they also presented their high rates of false-positive results. Here, we aimed to evaluate the relationship between the UroVysion tests and subsequent intravesical recurrence. METHODS: In the previous study, patients without bladder cancer during the first analysis showed the same examination set repeated 3 months later as the second analysis. In this follow-up study, 326 patients showed negative findings confirmed on cystoscopy during the second UroVysion test. Recurrence-free survival was assessed using a median follow-up of 27 months. RESULTS: In the two consecutive UroVysion tests, 214 patients (65.6%) showed negative UroVysion results in both tests, whereas 91 presented a positive result on either tests and 21 patients presented positive results in both tests. During the follow-up, 40 patients (12.3%) had an intravesical recurrence with non-muscle-invasive bladder cancer. The recurrence rates in patients with negative results in both tests, those with one positive result in either tests, and those with positive results in both tests were 8.4%, 16.5%, and 33.3%, respectively. The multivariate analysis indicated that the history of bladder cancer and the consecutive UroVysion test pattern were independent risk factors for recurrence. CONCLUSIONS: Our data confirmed the effectiveness of two consecutive UroVysion tests in predicting intravesical recurrence after TURBT. Further prospective studies would help determine an appropriate interval for cystoscopy follow-up.