Papers - Oya, Mototsugu

On-treatment C-reactive protein control could predict response to subsequent anti-PD-1 treatment in metastatic renal cell carcinoma.

Kimiharu Takamatsu, Ryuichi Mizuno, Yuto Baba, Yota Yasumizu, Nobuyuki Tanaka, Suguru Shirotake, Toshikazu Takeda, Shinya Morita, Kazuhiro Matsumoto, Takeo Kosaka, Hiroshi Asanuma, Masafumi Oyama, Shuji Mikami, Mototsugu Oya

International journal of clinical oncology (International Journal of Clinical Oncology)  26 ( 8 ) 1500 - 1505 2021.08

Research paper (scientific journal), Joint Work,  ISSN  1341-9625

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OBJECTIVE: The aim of this study was to evaluate the clinical significance of the on-treatment C-reactive protein (CRP) status during systemic treatment as the predictive marker for the response of subsequent nivolumab monotherapy in patients with refractory metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: A total of 73 mRCC patients treated with nivolumab were retrospectively reviewed. We evaluated the serum CRP levels before and after molecular-targeted treatments. Patients whose CRP did not exceed baseline value were defined as the CRP-control group and the others were defined as the CRP-progression group. The clinical impact of CRP-control on the efficacy of nivolumab was assessed. RESULTS: Twenty-four patients (33%) were categorized into the CRP-control group. The CRP-control group patients (median PFS not reached) had significantly longer PFS than the CRP-progression group (median PFS 11.9 months, 95% confidence interval, CI 4.1-19.8, p = 0.038). The CRP-control group had a tendency of longer OS from nivolumab initiation than the CRP-progression group (p = 0.071). By multivariate analysis, the on-treatment CRP-control was the independent predictive factor for PFS (hazard ratio HR 0.37, 95% CI 0.14-0.99, p = 0.047). CONCLUSION: The on-treatment CRP-control could be the predictive factor for the efficacy of nivolumab in refractory mRCC patients.

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Diagnostic performance of the vesical imaging-reporting and data system for detecting muscle-invasive bladder cancer in real clinical settings: Comparison with diagnostic cystoscopy.

Ryohei Kufukihara, Eiji Kikuchi, Keisuke Shigeta, Koichiro Ogihara, Yuki Arita, Hirotaka Akita, Tatsuya Suzuki, Takayuki Abe, Ryuichi Mizuno, Masahiro Jinzaki, Mototsugu Oya

Urologic oncology (Urologic Oncology: Seminars and Original Investigations)  40 ( 2 ) 61.e1 - 61.e8 2021.07

Research paper (scientific journal), Joint Work,  ISSN  1078-1439

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PURPOSE: We herein compared the diagnostic performance of Vesical Imaging-Reporting and Data System (VI-RADS) scoring with diagnostic cystoscopy and evaluated diagnostic accuracies based on tumor locations. MATERIALS AND METHODS: Among 112 bladder cancer patients who underwent multiparametric magnetic resonance imaging and diagnostic cystoscopy preoperatively to detect bladder cancer, 61 were analyzed. VI-RADS was categorized into 5 stages by 2 radiologists (R1 and R2). Cut-off values ≥3 indicated muscle-invasive bladder cancer (MIBC). Muscle invasion (MI) was visually evaluated using diagnostic cystoscopy by 2 urologists (U1 and U2). The sensitivity and specificity of VI-RADS scores and diagnostic cystoscopy for diagnosing MI were compared. RESULTS: 16 patients (26.2%) were pathologically diagnosed with MIBC. Regarding MI diagnostic accuracy, the sensitivity/specificity of VI-RADS scores were 93.8/88.9% by R1 and 87.5/86.7% by R2, while those of diagnostic cystoscopy were 56.3/68.9% by U1 and 68.8/84.4% by U2. Therefore, the diagnostic accuracy of VI-RADS was significantly higher than that of cystoscopy, particularly for tumors located on the bladder neck, trigone, dome, and posterior and anterior walls. Over- and under-diagnosis rates were higher with VI-RADS than with diagnostic cystoscopy (25.9% vs. 14.8%) for tumors located on the lateral wall or ureteral orifice. CONCLUSION: VI-RADS had superior diagnostic performance for detecting MI, especially in tumors located at the bladder neck/trigone/dome/posterior and anterior wall. However, VI-RADS was inferior to cystoscopy in terms of MI detection for tumors located on the lateral wall or ureteral orifice. Therefore, a combination of diagnostic tools is recommended for the accurate staging of these tumors.

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Germline Whole-Gene Deletion of FH Diagnosed from Tumor Profiling.

Arisa Ueki, Kokichi Sugano, Kumiko Misu, Eriko Aimono, Kohei Nakamura, Shigeki Tanishima, Nobuyuki Tanaka, Shuji Mikami, Akira Hirasawa, Miho Ando, Teruhiko Yoshida, Mototsugu Oya, Hiroshi Nishihara, Kenjiro Kosaki

International journal of molecular sciences (International Journal of Molecular Sciences)  22 ( 15 )  2021.07

Joint Work,  ISSN  16616596

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Hereditary leiomyomatosis and renal cell carcinoma (HL (RCC)) entails cutaneous and uterine leiomyomatosis with aggressive type 2 papillary RCC-like histology. HLRCC is caused by pathogenic variants in the FH gene, which encodes fumarate hydratase (FH). Here, we describe an episode of young-onset RCC caused by a genomic FH deletion that was diagnosed via clinical sequencing. A 35-year-old woman was diagnosed with RCC and multiple metastases: histopathological analyses supported a diagnosis of FH-deficient RCC. Although the patient had neither skin tumors nor a family history of HLRCC, an aggressive clinical course at her age and pathological diagnosis of FH-deficient RCC suggested a germline FH variant. After counseling, the patient provided written informed consent for germline genetic testing. She was simultaneously subjected to paired tumor profiling tests targeting the exome to identify a therapeutic target. Although conventional germline sequencing did not detect FH variants, exome sequencing revealed a heterozygous germline FH deletion. As such, paired tumor profiling, not conventional sequencing, was required to identify this genetic deletion. RCC caused by a germline FH deletion has hitherto not been described in Japan, and the FH deletion detected in this patient was presumed to be of maternal European origin. Although the genotype-phenotype correlation in HLRCC-related tumors is unclear, the patient's family was advised to undergo genetic counseling to consider additional RCC screening.

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Prognostic value of programmed death-ligand 1 status in Japanese patients with renal cell carcinoma.

Motohide Uemura, Noboru Nakaigawa, Naoto Sassa, Katsunori Tatsugami, Kenichi Harada, Toshinari Yamasaki, Nobuaki Matsubara, Takuya Yoshimoto, Yuki Nakagawa, Tamaki Fukuyama, Mototsugu Oya, Nobuo Shinohara, Hirotsugu Uemura, Toyonori Tsuzuki

International journal of clinical oncology (International Journal of Clinical Oncology)  26 ( 11 ) 2073 - 2084 2021.07

Research paper (scientific journal), Joint Work,  ISSN  1341-9625

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BACKGROUND: Programmed death-ligand 1 (PD-L1) positivity is associated with poor prognosis in renal cell carcinoma (RCC). Because the prognostic impact and effect of confounding factors are less known, we investigated the prognostic significance of PD-L1 expression in Japanese patients with recurrent/metastatic RCC who started systemic therapy in 2010-2015. METHODS: This multicenter, retrospective study recruited patients from 29 Japanese study sites who had prior systemic therapy for RCC (November 2018 to April 2019) and stored formalin-fixed paraffin-embedded primary lesion samples. The primary outcome was overall survival (OS) by PD-L1 expression. Secondary outcomes included OS in subgroups and duration of first- and second-line therapies by PD-L1 expression. OS distributions were estimated using Kaplan-Meier methodology. RESULTS: PD-L1 expression (on immune cells [IC] ≥ 1%) was observed in 315/770 (40.9%) patients. PD-L1 positivity was more prevalent in patients with poor risk per both Memorial Sloan Kettering Cancer Center [MSKCC] and International Metastatic RCC Database Consortium, and high-risk pathological features (higher clinical stage, nuclear grade and sarcomatoid features). Median OS for PD-L1-positive patients was 30.9 months (95% CI 25.5-35.7) versus 37.5 months (95% CI 34.0-42.6) for PD-L1-negative patients (HR 1.04 [90% CI 0.89-1.22, p = 0.65]; stratified by MSKCC risk and liver metastases). Propensity score weight (PSW)-adjusted OS was similar between PD-L1-positive and -negative patients (median 34.4 versus 31.5 months; estimated PSW-adjusted HR 0.986). CONCLUSIONS: This study suggests PD-L1 status was not an independent prognostic factor in recurrent/metastatic RCC during the study period because PD-L1 positivity was associated with poor prognostic factors, especially MSKCC risk status.

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Long-term efficacy and safety of iron-based phosphate binders, ferric citrate hydrate and sucroferric oxyhydroxide, in hemodialysis patients.

Yoshida T, Morimoto K, Kaburagi N, Fujino T, Takemitsu TY, Yamashita N, Oya M

International urology and nephrology (International Urology and Nephrology)  54 ( 4 ) 861 - 872 2021.07

ISSN  0301-1623

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Purpose: Iron-based phosphate binders, including ferric citrate hydrate (FCH) and sucroferric oxyhydroxide (SFOH), have been used for the treatment of hyperphosphatemia in end-stage renal disease patients on dialysis. However, the long-term efficacy and safety of these agents have not yet been clearly elucidated. Methods: Laboratory data of 56 hemodialysis patients who had been prescribed either FCH (n = 33) or SFOH (n = 23) were retrospectively examined. Results: We showed that both FCH and SFOH significantly and consistently decreased serum phosphate concentrations in the patients undergoing maintenance hemodialysis during the 36-month observation period. Serum levels of calcium, intact parathyroid hormone, as well as hemoglobin levels were unaltered. No overshoot of parameters of iron metabolism, such as transferrin saturation and serum ferritin levels, was observed, and serum ferritin level remained under 300 ng/mL in most patients. A trend towards decrease in the doses of erythropoiesis-stimulating agents used and frequency of intravenous iron use was observed in both treatment groups. No severe adverse drug reactions were observed in either the patients receiving FCH or SFOH. Conclusion: The results of the present study suggest that the iron-based phosphate binders, FCH and SFOH, decrease serum phosphate concentrations consistently and are safe to use over the long-term in maintenance hemodialysis patients.

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Amiodarone-induced multiple organ damage in an Alström syndrome patient with end-stage renal disease and hepatic cirrhosis.

Torimitsu T, Yoshida T, Makiuchi S, Itoh H, Oya M

CEN case reports (CEN case reports)  11 ( 1 ) 11 - 16 2021.07

ISSN  2192-4449

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Alström syndrome (AS) is an extremely rare disease accompanied by blindness, hearing loss, obesity, type 2 diabetes, dilated cardiomyopathy, and progressive hepatic and renal dysfunction. The life span of AS patients rarely exceeds 50 years, and thus there are very few reports describing the implementation of renal replacement therapy for these patients. We here report a case of AS patient who exhibited dilated cardiomyopathy, end-stage renal disease, and hepatic cirrhosis. He underwent hemodialysis therapy more than 3 years. Although he eventually died of amiodarone-induced multiple organ damage in the lungs and liver, the present case suggests that hemodialysis therapy can be a choice of renal replacement therapy for AS patients with end-stage renal disease.

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Genomic characterization of circulating tumor DNA in advanced genitourinary cancer patients SCRUM-Japan MONSTAR SCREEN

Nonomura Norio, Kato Taigo, Fujisawa Takao, Shiota Masaki, Eto Masatoshi, Osawa Takahiro, Abe Takashige, Shinohara Nobuo, Yasumizu Ryota, Tanaka Nobuyuki, Oya Mototsugu, Nishimoto Koshiro, Horasawa Satoshi, Kuramoto Naomi, Nakamura Yoshiaki, Taniguchi Hiroya, Yoshino Takayuki, Matsubara Nobuaki

ANNALS OF ONCOLOGY 32   S284 - S284 2021.07

ISSN  0923-7534

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Prominent response to platinum-based chemotherapy in a patient with <i>BRCA2</i> mutant-neuroendocrine prostate cancer and <i>MDM2</i> amplification.

Daimon T, Kosaka T, Hongo H, Aimono E, Nakamura K, Mikami S, Nishihara H, Oya M

IJU case reports (IJU Case Reports)  4 ( 4 ) 216 - 219 2021.07

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Introduction: Genomic profiling provides useful information for diagnosis, treatment, and prognosis, and detection of certain defects, such as DNA repair gene aberrations or microsatellite instability, can possibly lead to optimal treatment, but this testing has not been widely used to inform prostate cancer treatment. Case presentation: A 55-year-old man sequentially treated for prostate cancer was diagnosed as neuroendocrine prostate cancer from prostate specimens resected because of urinary retention. Subsequently, he received five cycles of platinum-based chemotherapy in total and responded well. We also performed next-generation sequencing of a sample from the prostate specimen and identified a breast cancer susceptibility gene mutation with Murine Double Minute 2 amplification and loss of heterozygosity in retinoblastoma 1. Conclusion: We report a neuroendocrine prostate cancer patient with Murine Double Minute 2 amplification who experienced an aggressive course and for whom platinum-based chemotherapy was effective, and one of the reasons for the good response might be the breast cancer susceptibility gene mutation.

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MUC1-C activates the PBAF chromatin remodeling complex in integrating redox balance with progression of human prostate cancer stem cells.

Hagiwara M, Fushimi A, Yamashita N, Bhattacharya A, Rajabi H, Long MD, Yasumizu Y, Oya M, Liu S, Kufe D

Oncogene (Oncogene)  40 ( 30 ) 4930 - 4940 2021.07

ISSN  0950-9232

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The polybromo-associated PBAF (SWI/SNF) chromatin remodeling complex, which includes PBRM1, ARID2, and BRD7, regulates cell differentiation and genomic integrity. MUC1-C is an oncogenic protein that drives lineage plasticity in prostate cancer (PC) progression. The present work demonstrates that MUC1-C induces PBRM1, ARID2, and BRD7 expression by the previously unrecognized E2F1-mediated activation of their respective promoters. The functional significance of the MUC1-C→PBAF pathway is supported by demonstrating involvement of MUC1-C in associating with nuclear PBAF and driving the NRF2 antioxidant gene transcriptome in PC cells. Mechanistically, MUC1-C forms a complex with NRF2 and PBRM1 on the NRF2 target SLC7A11 gene that encodes the xCT cystine-glutamate antiporter, increases chromatin accessibility and induces SLC7A11/xCT expression. We also show that MUC1-C and PBRM1 are necessary for induction of other NRF2 target genes, including G6PD and PGD that regulate the pentose phosphate pathway. Our results further demonstrate that MUC1-C integrates activation of PBRM1 with the regulation of antioxidant genes, ROS levels, pluripotency factor expression and the cancer stem cell (CSC) state. These findings reveal a role for MUC1-C in regulating PBAF, redox balance and lineage plasticity of PC CSC progression. Our findings also uncover involvement of MUC1-C in integrating the PBAF and BAF pathways in cancer.

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Subtype-specific collaborative transcription factor networks are promoted by OCT4 in the progression of prostate cancer.

Ken-Ichi Takayama, Takeo Kosaka, Takashi Suzuki, Hiroshi Hongo, Mototsugu Oya, Tetsuya Fujimura, Yutaka Suzuki, Satoshi Inoue

Nature communications (Nature Communications)  12 ( 1 ) 3766 - 3766 2021.06

Research paper (scientific journal), Joint Work,  ISSN  2041-1723

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Interactive networks of transcription factors (TFs) have critical roles in epigenetic and gene regulation for cancer progression. It is required to clarify underlying mechanisms for transcriptional activation through concerted efforts of TFs. Here, we show the essential role of disease phase-specific TF collaboration changes in advanced prostate cancer (PC). Investigation of the transcriptome in castration-resistant PC (CRPC) revealed OCT4 as a key TF in the disease pathology. OCT4 confers epigenetic changes by promoting complex formation with FOXA1 and androgen receptor (AR), the central signals for the progression to CRPC. Meanwhile, OCT4 facilitates a distinctive complex formation with nuclear respiratory factor 1 (NRF1) to gain chemo-resistance in the absence of AR. Mechanistically, we reveal that OCT4 increases large droplet formations with AR/FOXA1 as well as NRF1 in vitro. Disruption of TF collaborations using a nucleoside analogue, ribavirin, inhibited treatment-resistant PC tumor growth. Thus, our findings highlight the formation of TF collaborations as a potent therapeutic target in advanced cancer.

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CD8-positive T cells and CD204-positive M2 macrophages predict postoperative prognosis of very high-risk prostate cancer

Yanai Y., Kosaka T., Mikami S., Yasumizu Y., Takeda T., Matsumoto K., Kitano S., Oya M.

EUROPEAN UROLOGY 79   S1398 - S1399 2021.06

ISSN  0302-2838

Xp11.2転座型腎細胞癌においてInterleukin-6はprogrammed cell death-1 ligand(PDL1)発現を誘導する

高松 公晴, 水野 隆一, 田中 伸之, 浅沼 宏, 大家 基嗣

日本小児泌尿器科学会雑誌 (日本小児泌尿器科学会)  30 ( 1 ) 17 - 20 2021.06

ISSN  1341-0784

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【目的】Xp11.2転座/transcription factor enhancer3融合遺伝子関連腎細胞癌(Xp-RCC)は小児〜AYA世代の腎細胞癌(RCC:renal cell carcinoma)で最多の組織型だが、PDL1発現に関する報告は少ない。本研究ではXp-RCCにおけるPDL1発現と、炎症性サイトカインであるInterleukin-6(IL6)とPDL1発現の関連を評価した。【方法】RCC112検体(Xp-RCC7例、淡明細胞型RCC105例)を対象に免疫染色によりPDL1発現率を評価した。更に各種ヒトRCC細胞株(786-O、Caki2、ACHN)とXp-RCC細胞株(S-TFE)を用いてIL6刺激によるPDL1発現の変化を評価した。【結果】Xp-RCCではPDL1陽性率が57%で、淡明細胞型(25%)よりもPDL1陽性率が高い傾向がみられた(p=0.091)。IL6刺激によりS-TFE(p=0.014)、786O(p=0.011)、Caki2(p=0.016)、ACHN(p=0.002)でPDL1発現が上昇した。IL6+IL6中和抗体付加により、S-TFE(p=0.006)、786O(p=0.026)、Caki2(p=0.025)、ACHN(p=0.021)でIL6によるPDL1発現誘導効果は有意に抑制された。【結論】Xp-RCCでは淡明細胞型RCCと比較してPDL1発現が高い傾向を認めた。Xp-RCC細胞株(S-TFE)ではIL6刺激によりPDL1発現が誘導されることが示唆された。(著者抄録)

Overview of recent progress on steady state operation of all-metal plasma facing wall device QUEST

Hanada K., Yoshida N., Hasegawa M., Oya M., Oya Y., Takagi I, Hatayama A., Shikama T., Idei H., Nagashima Y., Ikezoe R., Onchi T., Kuroda K., Kawasaki S., Higashijima A., Nagata T., Shimabukuro S., Nakamura K., Murakami S., Takase Y., Gao X., Liu H., Qian J.

NUCLEAR MATERIALS AND ENERGY 27 2021.06

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Isocitrate dehydrogenase 2 regulates intracellular metabolic reprogramming in chemoresistant urothelial carcinoma

Shigeta K., Hasegawa M., Kosaka T., Hishiki T., Ryuichi M., Miyajima A., Suematsu M., Kikuchi E., Oya M.

EUROPEAN UROLOGY 79   S632 - S633 2021.06

ISSN  0302-2838

Diagnostic performance of vesical imaging-reporting and data system for detecting muscle-invasive bladder cancer in real clinical setting: Comparison to diagnostic cystoscopy

Shigeta K., Kufukihara R., Ogihara K., Arita Y., Akita H., Suzuki T., Mizuno R., Kikuchi E., Jinzaki M., Oya M.

EUROPEAN UROLOGY 79   S1006 - S1007 2021.06

ISSN  0302-2838

Comparison of clinicopathological characteristics between primary muscle-invasive bladder cancer and secondary muscle invasive bladder recurrence subsequent to upper tract urothelial carcinoma

Shigeta K., Matsumoto K., Yasumizu Y., Tanaka N., Takeda T., Kosaka T., Mizuno R., Kikuchi E., Oya M.

EUROPEAN UROLOGY 79   S1081 - S1082 2021.06

ISSN  0302-2838

Germline BRCA2 mutation in a case of aggressive prostate cancer accompanied by spinal bulbar muscular atrophy.

Hiroshi Hongo, Takeo Kosaka, Hideyuki Hayashi, Kohei Nakamura, Hiroshi Nishihara, Shuji Mikami, Himisha Beltran, Mototsugu Oya

Asian journal of andrology (Asian Journal of Andrology)  24 ( 1 ) 116 - 118 2021.05

Joint Work,  ISSN  1008-682X

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Analysis of the CLEAR study in patients (pts) with advanced renal cell carcinoma (RCC): Depth of response and efficacy for selected subgroups in the lenvatinib (LEN) plus pembrolizumab (PEMBRO) and sunitinib (SUN) treatment arms.

Grunwald Viktor, Powles Thomas, Kopyltsov Evgeny, Kozlov Vadim, Gordoa Teresa Alonso, Eto Masatoshi, Hutson Thomas E., Motzer Robert J., Winquist Eric, Maroto-Rey Pablo, Keam Bhumsuk, Procopio Giuseppe, Wong Shirley, Melichar Bohuslav, Rolland Frederic, Oya Mototsugu, Rodriguez-Lopez Karla, Saito Kenichi, Smith Alan D., Porta Camillo

JOURNAL OF CLINICAL ONCOLOGY 39 ( 15 )  2021.05

ISSN  0732-183X

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Guideline adherence for radical cystectomy significantly affects survival outcomes in non-muscle-invasive bladder cancer patients

Emina Kayama, Keisuke Shigeta, Eiji Kikuchi, Koichiro Ogihara, Kyohei Hakozaki, Tomohiro Iwasawa, Ken Kamisawa, Kunimitsu Kanai, Hiroki Ide, Satoshi Hara, Ryuichi Mizuno, Mototsugu Oya

Japanese Journal of Clinical Oncology (Oxford University Press (OUP))  51 ( 8 ) 1303 - 1312 2021.05

Research paper (scientific journal), Joint Work,  ISSN  0368-2811

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<title>Abstract</title>
<sec>
<title>Background</title>
The relationship between guideline adherence for radical cystectomy of non-muscle-invasive bladder cancer and patient prognoses currently remains unclear. We investigated whether guideline adherence at the time of non-muscle-invasive bladder cancer affects the oncological outcomes of bladder cancer patients who underwent radical cystectomy.


</sec>
<sec>
<title>Methods</title>
Among 267 cTa-4N0-2M0 bladder cancer patients, 70 who underwent radical cystectomy under the non-muscle-invasive bladder cancer or muscle-invasive bladder cancer status that progressed from non-muscle-invasive bladder cancer were identified. Patients who followed the guidelines from initial transurethral resection of bladder tumors to radical cystectomy were defined as the guideline adherent group (n = 52), while those who did not were the guideline non-adherent group (n = 18).


</sec>
<sec>
<title>Results</title>
In the guideline non-adherent group, 8 (44.4%) out of 18 were diagnosed with highest risk non-muscle-invasive bladder cancer for Bacillus Calmette Guérin-naïve patients and 7 (38.9%) had a Bacillus Calmette Guérin unresponsive tumor status. Five-year recurrence-free survival and cancer-specific survival rates for the guideline non-adherent group vs guideline adherent group were 38.9% vs 69.8% (P = 0.018) and 52.7% vs 80.1% (P = 0.006), respectively. A multivariate analysis identified guideline non-adherence as one of independent indicators for disease recurrence (hazard ratio = 2.81, P = 0.008) and cancer-specific death (hazard ratio = 4.04, P = 0.003). In a subgroup analysis of 49 patients with cT1 or less non-muscle-invasive bladder cancer at the time of radical cystectomy, guideline non-adherence remained an independent prognostic factor for cancer-specific survival (hazard ratio = 3.46, P = 0.027).


</sec>
<sec>
<title>Conclusions</title>
Guideline adherence during the time course of the non-muscle-invasive bladder cancer stage may result in a favorable prognosis of patients who receive radical cystectomy. Even under non-muscle-invasive bladder cancer status, radical cystectomy needs to be performed with adequate timing under guideline recommendations.


</sec>

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First case of ductal adenocarcinoma of the prostate with MAP3K1 homozygous deletion.

Kazunori Shojo, Takeo Kosaka, Kohei Nakamura, Hiroshi Hongo, Hiroaki Kobayashi, Shuji Mikami, Hiroshi Nishihara, Mototsugu Oya

IJU case reports (IJU Case Reports)  4 ( 3 ) 176 - 179 2021.05

Joint Work

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Introduction: Ductal adenocarcinoma of the prostate is a rare prostate cancer variant and associated with higher stage and greater risk of mortality. Optimal systemic therapy for metastatic ductal adenocarcinoma is not known. Case presentation: A 67-year-old man presented with ductal adenocarcinoma of the prostate accompanied by multiple lung metastases and advanced bone metastases. We performed channel transurethral resection of the prostate and confirmed the diagnosis of ductal adenocarcinoma of the prostate. DNA sequencing identified a TP53 somatic point mutation (p.Gly245Ser) as the pathogenic variant. Furthermore, a homozygous deletion was observed in mitogen-activated protein kinase kinase kinase 1. The patient received enzalutamide but deceased 5 months after presenting to our institution. Conclusion: To our knowledge, this is the first report of ductal adenocarcinoma of the prostate with a mitogen-activated protein kinase kinase kinase 1 homozygous deletion. Accumulation of whole-exome sequencing data is expected to inform future advances in therapy development.

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