Papers - Oya, Mototsugu

Biomarkers Towards New Era of Therapeutics for Metastatic Renal Cell Carcinoma

Mizuno Ryuichi, Oya Mototsugu

KIDNEY CANCER 4 ( 2 ) 61 - 69 2020

ISSN  2468-4562

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膀胱・前立腺/腟・子宮横紋筋肉腫　機能温存と再建術

浅沼 宏, 大家 基嗣

小児外科 52   1270 - 1275 2020

Splenic cord capillary hemangioma with non-islet cell tumor hypoglycemia: a case report.

Tatsuaki Daimon, Takeo Kosaka, Minoru Horinaga, Junichi Saito, Yoshito Ueyama, Shoji Matsuzaki, Mototsugu Oya

Diagnostic pathology (BMC)  14 ( 1 ) 135 - 135 2019.12

Research paper (scientific journal), Joint Work

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BACKGROUND: Splenic cord capillary hemangioma is a rare benign vascular lesion classified as a splenic hamartoma. On the other hand, non-islet cell tumor hypoglycemia (NICTH) is one of the rare causes of spontaneous hypoglycemia and is considered to be one of the paraneoplastic syndromes. To the best of our knowledge, this is the first reported case of a splenic cord capillary hemangioma with NICTH. CASE PRESENTATION: A 25-year-old male was referred to our hospital with hypoglycemia. Except for his low blood sugar, there were no abnormal findings from laboratory tests, which included an endocrinological examination. Enhanced computed tomography confirmed the presence of a solid mass measuring about 6 cm in the retroperitoneum, and a tumorectomy was performed. During this operation, it became clear that the tumor turned out to be a splenic parenchyma, and as a result, a total splenectomy was performed. Microscopically, we diagnosed this as a cord capillary hemangioma, and through immunohistochemistry, we found that some tumor cells were positive for insulin-like growth factor -II. Fortunately, the hypoglycemia-related symptoms disappeared after surgical resection was performed. The patient is still alive and well without evidence of local tumor recurrence 15 years after the operation. CONCLUSIONS: Splenic cord capillary hemangioma, one of the types of splenic hamartomas, is a very rare benign vascular lesion and might be associated with hypoglycemia thought to be NICTH.

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ASO Author Reflections: Could Laparoscopic Surgery Have the Same Long-Term Oncological Outcomes as Open Radical Nephroureterectomy in T3N0M0 Upper Tract Urothelial Carcinoma? A Multicenter Cohort Study Adjusted by Propensity Score Matching.

Keisuke Shigeta, Eiji Kikuchi, Mototsugu Oya

Annals of surgical oncology (SPRINGER)  26 ( Suppl 3 ) 815 - 816 2019.12

Research paper (scientific journal), Joint Work,  ISSN  1068-9265

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A first Japanese case of neuroendocrine prostate cancer accompanied by lung and brain metastasis with somatic and germline BRCA2 mutation.

Takeo Kosaka, Hiroshi Hongo, Eriko Aimono, Kazuhiro Matsumoto, Tetsu Hayashida, Shuji Mikami, Hiroshi Nishihara, Mototsugu Oya

Pathology international (WILEY)  69 ( 12 ) 715 - 720 2019.12

Research paper (scientific journal), Joint Work, Accepted,  ISSN  1320-5463

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Germline mutations and copy number changes in DNA damage repair (DDR) genes such as BRCA2 are associated with aggressive forms of prostate cancer (PCa). Although the prevalence of BRCA2 variants in PCa is increasing in Japan, the genomic and biological implications in Japanese patients are unclear. An 81-year-old male presented with prostatic adenocarcinoma with neuroendocrine differentiation accompanied by metastatic lung nodule and brain metastases. Platinum-based doublet chemotherapy combined with etoposide resulted in partial and complete remissions of brain and lung metastases, respectively. Next-generation sequencing of biopsy and peripheral blood samples demonstrated a somatic BRCA2 mutation at c.7008-2A>C and a germline mutation at p.E2877*. The patient's son had been diagnosed with breast cancer 2.5 years ago and was found to have the same germline BRCA2 mutation. BRCA2 mutation increases the risks of aggressive PCa and other cancer types in Japanese males. These forms may be highly responsive to platinum-based chemotherapy.

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Biopsy-diagnosed renal granuloma after intravesical bacillus Calmette-Guérin therapy for bladder carcinoma: a case series and review of the literature.

Keiichi Narita, Hirotaka Akita, Eiji Kikuchi, Tadaki Nakahara, Shigeo Okuda, Seishi Nakatsuka, Mototsugu Oya, Masahiro Jinzaki

BJR case reports (BRITISH INST RADIOLOGY)  5 ( 4 )  2019.12

Joint Work,  ISSN  2055-7159

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Renal granuloma is a rare complication affecting the kidneys after intravesical bacillus Calmette-Guérin (BCG) therapy for bladder carcinoma. Our case series review describes the imaging and histopathological findings of BCG-induced renal granulomas. All three renal granulomas, which were located in the upper pole, had a solitary mass-like appearance. The mean diameter was 31.3 mm. In the two cases, the lesion was homogeneously enhanced on post-contrast CT, and presented homogeneous low signal intensity on T2 weighted imaging (T2WI) and iso-signal intensity on diffusion-weighted imaging (DWI). Both lesions had increased fludeoxyglucose (FDG) uptake. Histological examinations revealed granulomatous inflammation with fibrosis. The third case showed a lesion having heterogeneous enhancement on CT, heterogeneous and slightly high signal intensity on T2WI, and high signal intensity on DWI. This case showed more severe inflammatory cell infiltration and less fibrosis than the former two cases did. It was suggested that the signal intensity on T2WI and DWI depends on the degree of inflammation and fibrosis in renal granuloma. It is currently challenging to distinguish renal granuloma from renal malignancy based on only imaging findings. Biopsies were helpful in confirming the diagnosis and avoiding unnecessary resection. Renal granuloma should be considered as a differential diagnosis when a renal mass is found in a patient with a history of intravesical BCG treatment.

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Classification of solid renal tumor with oncocytic/eosinophilic cytoplasm: is hybrid oncocytic/chromophobe renal tumor a subtype of oncocytoma, chromophobe renal cell carcinoma, or a distinct tumor entity?

Shuji Mikami, Naoto Kuroda, Yoji Nagashima, Chisato Ohe, Hiroyuki Hayashi, Ryuichi Mizuno, Mototsugu Oya, Kaori Kameyama

Annals of translational medicine (AME PUBL CO)  7 ( Suppl 8 ) S350 2019.12

Joint Work,  ISSN  2305-5839

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A very-high-energy component deep in the Gamma-ray Burst afterglow

H. Abdalla R. Adam F. Aharonian F. Ait Benkhali E. O. Anguener M. Arakawa, C. Arcaro, C. Armand, H. Ashkar, M. Backes, V. Barbosa Martins, M. Barnard Y. Becherini, D. Berge, K. Bernloehr, E. Bissaldi, R. Blackwell, M. Boettcher, C. Boisson, J. Bolmont, S. Bonnefoy, J. Bregeon, M. Breuhaus, F. Brun, P. Brun, M. Bryan, M. Buechele, T. Bulik, T. Bylund, M. Capasso, S. Caroff, A. Carosi, S. Casanova, M. Cerruti, T. Chand, S. Chandra, A. Chen, S. Colafrancesco, M. Curylo, I. D. Davids, C. Deil, J. Devin, P. deWilt, L. Dirson, A. Djannati-Atai, A. Dmytriiev, A. Donath, V. Doroshenko, J. Dyks, K. Egberts, G. Emery, J. -P. Ernenwein, S. Eschbach, K. Feijen, S. Fegan, A. Fiasson, G. Fontaine, S. Funk, M. Fuessling, S. Gabici, Y. A. Gallant, F. Gate, G. Giavitto, L. Giunti, D. Glawion, J. F. Glicenstein, D. Gottschall, M. -H. Grondin, J. Hahn, M. Haupt, G. Heinzelmann, G. Henri, G. Hermann, J. A. Hinton, W. Hofmann, C. Hoischen, T. L. Holch, M. Holler, D. Horns, D. Huber, H. Iwasaki, M. Jamrozy, D. Jankowsky, F. Jankowsky, A. Jardin-Blicq, I. Jung-Richardt, M. A. Kastendieck, K. Katarzynski, M. Katsuragawa, U. Katz, D. Khangulyan, B. Khelifi, J. King, S. Klepser, W. Kluzniak, N. Komin, K. Kosack, D. Kostunin, M. Kreter, G. Lamanna, A. Lemiere, M. Lemoine-Goumard, J. -P. Lenain, E. Leser, C. Levy, T. Lohse, I. Lypova, J. Mackey, J. Majumdar, D. Malyshev, V. Marandon, A. Marcowith, A. Mares, C. Mariaud, G. Marti-Devesa, R. Marx, G. Maurin, P. J. Meintjes, A. M. W. Mitchell, R. Moderski, M. Mohamed, L. Mohrmann, C. Moore, E. Moulin, J. Muller, T. Murach, S. Nakashima, M. de Naurois, H. Ndiyavala, F. Niederwanger, J. Niemiec, L. Oakes, P. O Brien, H. Odaka, S. Ohm, E. de Ona Wilhelmi, M. Ostrowski, I. Oya, M. Panter, R. D. Parsons, C. Perennes, P. -O. Petrucci, B. Peyaud, Q. Piel, S. Pita, V. Poireau, A. Priyana Noel, D. A. Prokhorov, H. Prokoph, G. Puehlhofer, M. Punch, A. Quirrenbach, S. Raab, R. Rauth, A. Reimer, O. Reimer, Q. Remy, M. Renaud, F. Rieger, L. Rinchiuso, C. Romoli, G. Rowell, B. Rudak, E. Ruiz-Velasco, V. Sahakian, S. Sailer, S. Saito, D. A. Sanchez, A. Santangelo, M. Sasaki, R. Schlickeiser, F. Schuessler, A. Schulz, H. M. Schutte, U. Schwanke, S. Schwemmer, M. Seglar-Arroyo, M. Senniappan, A. S. Seyffert, N. Shafi, K. Shiningayamwe, R. Simoni, A. Sinha, H. Sol, A. Specovius, M. Spir-Jacob, L. Stawarz, R. Steenkamp, C. Stegmann, C. Steppa, T. Takahashi, T. Tavernier, A. M. Taylor, R. Terrier, D. Tiziani, M. Tluczykont, C. Trichard, M. Tsirou, N. Tsuji, R. Tuffs, Y. Uchiyama, D. J. van der Walt, C. van Eldik, C. van Rensburg, B. van Soelen, G. Vasileiadis, J. Veh, C. Venter, P. Vincent, J. Vink, H. J. Voelk, T. Vuillaume, Z. Wadiasingh, S. J. Wagner, R. White, A. Wierzcholska, R. Yang, H. Yoneda, M. Zacharias, R. Zanin, A. A. Zdziarski, A. Zech, A. Ziegler, J. Zorn, N. Zywucka, F. de Palma, M. Axelsson, O. J. Roberts

 2019.11

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Gamma-ray bursts (GRBs) are brief flashes of gamma rays, considered to be the
most energetic explosive phenomena in the Universe. The emission from GRBs
comprises a short (typically tens of seconds) and bright prompt emission,
followed by a much longer afterglow phase. During the afterglow phase, the
shocked outflow -- produced by the interaction between the ejected matter and
the circumburst medium -- slows down, and a gradual decrease in brightness is
observed. GRBs typically emit most of their energy via gamma-rays with energies
in the kiloelectronvolt-to-megaelectronvolt range, but a few photons with
energies of tens of gigaelectronvolts have been detected by space-based
instruments. However, the origins of such high-energy (above one
gigaelectronvolt) photons and the presence of very-high-energy (more than 100
gigaelectronvolts) emission have remained elussive. Here we report observations
of very-high-energy emission in the bright GRB 180720B deep in the GRB
afterglow -ten hours after the end of the prompt emission phase, when the X-ray
flux had already decayed by four orders of magnitude. Two possible explanations
exist for the observed radiation: inverse Compton emission and synchrotron
emission of ultrarelativistic electrons. Our observations show that the energy
fluxes in the X-ray and gamma-ray range and their photon indices remain
comparable to each other throughout the afterglow. This discovery places
distinct constraints on the GRB environment for both emission mechanisms, with
the inverse Compton explanation alleviating the particle energy requirements
for the emission observed at late times. The late timing of this detection has
consequences for the future observations of GRBs at the highest energies.


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Advances in targeted alpha therapy for prostate cancer

De Vincentis G., Gerritsen W., Gschwend J.E., Hacker M., Lewington V., O'Sullivan J.M., Oya M., Pacilio M., Parker C., Shore N., Sartor O.

Annals of Oncology (Annals of Oncology)  30 ( 11 ) 1728 - 1739 2019.11

ISSN  09237534

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© 2019 THE AUTHORS Amongst therapeutic radiopharmaceuticals, targeted alpha therapy (TαT) can deliver potent and local radiation selectively to cancer cells as well as the tumor microenvironment and thereby control cancer while minimizing toxicity. In this review, we discuss the history, progress, and future potential of TαT in the treatment of prostate cancer, including dosimetry-individualized treatment planning, combinations with small-molecule therapies, and conjugation to molecules directed against antigens expressed by prostate cancer cells, such as prostate-specific membrane antigen (PSMA) or components of the tumor microenvironment. A clinical proof of concept that TαT is efficacious in treating bone-metastatic castration-resistant prostate cancer has been demonstrated by radium-223 via improved overall survival and long-term safety/tolerability in the phase III ALSYMPCA trial. Dosimetry calculation and pharmacokinetic measurements of TαT provide the potential for optimization and individualized treatment planning for a precision medicine-based cancer management paradigm. The ability to combine TαTs with other agents, including chemotherapy, androgen receptor-targeting agents, DNA repair inhibitors, and immuno-oncology agents, is under investigation. Currently, TαTs that specifically target prostate cancer cells expressing PSMA represents a promising therapeutic approach. Both PSMA-targeted actinium-225 and thorium-227 conjugates are under investigation. The described clinical benefit, safety and tolerability of radium-223 and the recent progress in TαT trial development suggest that TαT occupies an important new role in prostate cancer treatment. Ongoing studies with newer dosimetry methods, PSMA targeting, and novel approaches to combination therapies should expand the utility of TαT in prostate cancer treatment.

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A NOVEL RISK BASED APPROACH SIMULATING ONCOLOGIC SURVEILLANCE ACCORDING TO SMOKING STATUS AFTER RADICAL NEPHROURETERECTOMY WITH UPPER TRACT UROTHELIAL CARCINOMA

Shigeta Keisuke, Eiji Kikuchi, Masayuki Hagiwara, Takayuki Abe, Koichiro Ogihara, Ryuichi Mizuno, Mototsugu Oya

JOURNAL OF UROLOGY (LIPPINCOTT WILLIAMS & WILKINS)  30 ( 4 ) E1197 - E1197 2019.11

Joint Work,  ISSN  0923-7534

Neutrophil-to-lymphocyte ratio is a useful biomarker for predicting worse clinical outcome in chemo-resistant urothelial carcinoma patients treated with pembrolizumab

Ogihara K., Kikuchi E., Okabe T., Hattori S., Yamashita R., Yoshimine S., Shirotake S., Matsumoto K., Mizuno R., Hara S., Oyama M., Niwakawa M., Oya M.

ANNALS OF ONCOLOGY 30 2019.11

ISSN  0923-7534

TNFAIP2 expression induces epithelial-to-mesenchymal transition and confers platinum resistance in urothelial cancer cells.

Naoya Niwa, Nobuyuki Tanaka, Hiroshi Hongo, Yasumasa Miyazaki, Kimiharu Takamatsu, Ryuichi Mizuno, Eiji Kikuchi, Shuji Mikami, Takeo Kosaka, Mototsugu Oya

Laboratory investigation; a journal of technical methods and pathology (NATURE PUBLISHING GROUP)  99 ( 11 ) 1702 - 1713 2019.11

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0023-6837

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Cisplatin (CDDP)-based chemotherapy is the gold standard treatment for many types of cancer. However, the phenotypic hallmark of tumors often changes after CDDP treatment, with the acquisition of epithelial-to-mesenchymal transition (EMT) and platinum resistance. Furthermore, the mechanisms by which cancer cells acquire EMT under the control of CDDP remain unclear. Following an investigation of urothelial carcinoma (UC) before and after the acquisition of platinum resistance, we offer the new target TNFAIP2, which led to EMT and tumor invasion in platinum-treated UC cells. TNFAIP2 expression in cancer was examined at the protein and transcriptional levels. A potential target for TNFAIP2 during EMT was assessed by microarray. Clinically, upregulated TNFAIP2 expression was identified as a significant predictor of mortality following surgery in three different cohorts of patients with UC (n = 156, n = 119, and n = 54). Knockdown of TNFAIP2 resulted in upregulation of E-cadherin expression and downregulation of TWIST1 expression, which decreased motile function in platinum-resistant UC cells. TNFAIP2 overexpression led to downregulation of E-cadherin expression and upregulation of TWIST1 expression in platinum-naïve UC cells. Clinical investigation of matched pre- and post-CDDP-treated UC sections confirmed upregulation of TNFAIP2 expression in CDDP-treated tumors but downregulation of E-cadherin expression. Global gene expression analysis following TNFAIP2 knockdown identified MTDH as a positive regulator of TNFAIP2-derived EMT acquisition in cancer cells. The present results suggest a relationship between TNFAIP2 and EMT in cancers under the control of CDDP, in which MTDH expression levels in cancer cells are vital for promoting TNFAIP2-derived EMT acquisition.

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Renal Trauma Classification and Management: Validating the Revised Renal Injury Grading Scale

Satoshi Yazawa, Mototsugu Oya, Yosuke Nakajima

JOURNAL OF UROLOGY (LIPPINCOTT WILLIAMS & WILKINS)  202 ( 5 ) 1002 - 1002 2019.11

Joint Work,  ISSN  0022-5347

Usefulness of contrast-enhanced ultrasonography for diagnosis of renal cell carcinoma in dialysis patients: Comparison with computed tomography.

Masahiro Hashimoto, Kiyoshi Ohkuma, Hirotaka Akita, Yoshitake Yamada, Seishi Nakatsuka, Ryuichi Mizuno, Mototsugu Oya, Masahiro Jinzaki

Medicine (LIPPINCOTT WILLIAMS & WILKINS)  98 ( 47 ) e18053 2019.11

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0025-7974

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AIMS: To investigate the usefulness of contrast-enhanced ultrasonography for diagnosing renal cell carcinoma (RCC) in dialysis patients. MATERIAL AND METHODS: Of 1301 dialysis patients who underwent abdominal computed tomography (CT) between January 2012 and March 2017, 19 were suspected to have solid renal lesions; of these patients, 18 gave consent for and underwent contrast-enhanced ultrasonography with perflubutane in addition to CT; 13 underwent dynamic contrast-enhanced CT, and 5, who could not be administered iodinated contrast media, underwent unenhanced CT. The final diagnoses were based on histopathological findings or the presence/absence of enlargement of the lesion during follow-up. RESULTS: Of the 19 lesions in 18 patients, 14 were diagnosed as RCC and 5 as benign cysts. CT facilitated accurate diagnosis in 10/19 lesions (52.6%) with obvious enhancement (≥20 Hounsfield units [HU]), while definitive diagnosis by CT was difficult in 9 lesions: 2 lesions showed ambiguous enhancement (10-20 HU), 1 lesion was an inflammatory cyst with obvious enhancement, and 6 lesions were assessed by unenhanced CT. Compared with CT, contrast-enhanced ultrasonography allowed more accurate diagnosis (McNemar test, P = .02) in 17/19 lesions (89.5%, 14 RCC and 3 cysts; including all lesions assessed by unenhanced CT and 2 with ambiguous enhancement on CT), with 1 false-positive (inflammatory cyst with hyper-enhancement) and 1 false-negative result due to deep location of the lesion. CONCLUSIONS: Contrast-enhanced ultrasonography was useful for the diagnosis of RCC in dialysis patients with suspected solid renal lesions especially when contrast enhancement was not obvious on CT or contrast-enhanced CT could not be performed.

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特集 希少癌に備える-いざという時のための基礎知識 企画にあたって

大家 基嗣

臨床泌尿器科 (株式会社医学書院)  73 ( 11 ) 785 - 785 2019.10

ISSN  0385-2393

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特集 希少癌に備える-いざという時のための基礎知識 前立腺導管癌

小坂 威雄, 萩原 正幸, 大家 基嗣

臨床泌尿器科 (株式会社医学書院)  73 ( 11 ) 846 - 849 2019.10

ISSN  0385-2393

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Ductal adenocarcinoma of the prostate

Kosaka T., Hagiwara M., Oya M.

Japanese Journal of Clinical Urology (Japanese Journal of Clinical Urology)  73 ( 11 ) 846 - 849 2019.10

ISSN  03852393

Randomized phase III trial of avelumab plus axitinib vs sunitinib as first-line treatment for advanced renal cell carcinoma: JAVELIN renal 101 Japanese subgroup analysis

Uemura M., Tomita Y., Miyake H., Hatakeyama S., Kanayama H-O., Numakura K., Takagi T., Kato T., Eto M., Obara W., Uemura H., Motzer R. J., Fujii Y., Kamei Y., Oya M.

ANNALS OF ONCOLOGY 30 2019.10

ISSN  0923-7534

Long-Term Oncologic Outcomes of Laparoscopic Versus Open Radical Nephroureterectomy for Patients with T3N0M0 Upper Tract Urothelial Carcinoma: A Multicenter Cohort Study with Adjustment by Propensity Score Matching.

Keisuke Shigeta, Eiji Kikuchi, Takayuki Abe, Masayuki Hagiwara, Koichiro Ogihara, Tadanori Anno, Kota Umeda, Yuto Baba, Tansei Sanjo, Kazunori Shojo, Ryuichi Mizuno, Mototsugu Oya

Annals of surgical oncology (SPRINGER)  26 ( 11 ) 3774 - 3781 2019.10

Research paper (scientific journal), Joint Work, Accepted,  ISSN  1068-9265

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BACKGROUND: This study aimed to investigate the long-term oncologic outcomes of laparoscopic radical nephroureterectomy (LRNU) and open radical nephroureterectomy (ORNU) for patients with clinical and pathologic T3N0M0 upper tract urothelial carcinoma (UTUC). METHODS: Among 375 UTUC patients who underwent radical nephroureterectomy, this study identified 144 pT3N0M0 patients as cohort 1 after propensity score (PS) matching. Among 399 UTUC patients, the study identified 110 cT3N0M0 patients as cohort 2 after PS matching. Oncologic outcomes such as intravesical recurrence-free survival (IVRFS) and cancer-specific survival (CSS) were assessed by multivariate Cox's regression analysis. RESULTS: Cohort 1 of pT3N0M0 UTUC had 3-year CSS and IVRFS rates of 67.9 and 52.7%, respectively, in the LRNU group, which were significantly lower than in the ORNU group (81.4%, p = 0.039 and 71.6%, p = 0.046). The multivariate Cox's regression analysis identified the type of surgical approach (LRNU vs. ORNU) as one of the independent prognostic factors for CSS (hazard rate [HR], 1.88, p = 0.043) and IVRFS (HR, 1.75, p = 0.049). Cohort 2 of cT3N0M0 UTUC had 3-year CSS and IVRFS rates of 48.5 and 41.4%, respectively, in the LRNU group, which were significantly lower than in the ORNU group (65.8%, p = 0.049 and 67.2%, p = 0.047), and the type of surgical approach (LRNU vs. ORNU) remained as one of the independent prognostic factors for CSS and IVRFS. CONCLUSIONS: Based on clinical and pathologic T3N0M0 UTUC populations after PS adjustments, LRNU resulted in poorer CSS and IVRFS than ORNU.

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Japanese Case of Enzalutamide-Resistant Prostate Cancer Harboring a SPOP Mutation With Scattered Allelic Imbalance: Response to Platinum-Based Therapy.

Keitaro Watanabe, Takeo Kosaka, Eriko Aimono, Hiroshi Hongo, Shuji Mikami, Hiroshi Nishihara, Mototsugu Oya

Clinical genitourinary cancer (CIG MEDIA GROUP, LP)  17 ( 5 ) e897 - e902 2019.10

Research paper (scientific journal), Joint Work,  ISSN  1558-7673

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Genomic analysis of tumor biopsy specimens is critical for precision medicine, but there are no consensus guidelines on treatment plans for specific mutations. Herein we present a case of enzalutamide-resistant prostate cancer (PC) harboring a speckle-type pox virus and zinc finger protein (SPOP) mutation with scattered allelic imbalance successfully treated using platinum-based treatment.A 71-year-old man was diagnosed with castration-resistant PC and bone metastases. He was initial treated using enzalutamide and denosumab, and subsequently administrated radium-223. His prostate-specific antigen level initially decreased during treatment, but eventually began to rise.Magnetic resonance imaging revealed progressive PC invading the bladder, so we performed channeling transurethral resection of bladder tumor. The pathological diagnosis was adenocarcinoma with neuroendocrine differentiation.Carboplatin with etoposide therapy was initiated and no obvious tumor progression was detected thereafter. Genetic sequencing identified a SPOP p.Y87N mutation with scattered allelic imbalance.These findings suggest that enzalutamide-resistant PC with SPOP loss of function might be highly responsive to platinum-based therapy.Mutational analyses might provide useful information for treatment guidance of refractory PC. (C) 2019 Elsevier Inc. All rights reserved.

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