Unexpected tumor response to palliative pelvic radiotherapy in mismatch repair-deficient advanced prostate cancer: a cas

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Unexpected tumor response to palliative pelvic radiotherapy in mismatch repair‑deficient advanced prostate cancer: a case report Giovanni Aluisio1*  , Ercole Mazzeo1, Frank Lohr1, Federica Fiocchi2, Stefania Bettelli3, Cinzia Baldessari4, Maurizio Paterlini5 and Alessio Bruni1

Abstract  Background:  Mismatch-repair-deficiency resulting in microsatellite instability (MSI) may confer increased radiosensitivity in locally advanced/metastatic tumors and thus radiotherapy (RT) potentially might have a changing role in treating this subset of patients, alone or in combination with checkpoint inhibitors. Case presentation:  We report a 76 year-old Italian male patient presenting with locally advanced undifferentiated prostate cancer (LAPC), infiltrating bladder and rectum. Molecular analysis revealed high-MSI with an altered expression of MSH2 and MSH6 at immunohistochemistry. Two months after 6 chemotherapy cycles with Docetaxel associated to an LHRH analogue, a computed tomography scan showed stable disease. After palliative RT (30 Gy/10 fractions) directed to the tumor mass with a 3D-conformal setup, a follow-up computed tomography scan at 8 weeks revealed an impressive response that remained stable at computed tomography after 9 months, with sustained biochemical response. To our knowledge, this is the first case of such a sustained response to low dose RT alone in high-MSI LAPC. Conclusions:  Routine evaluation of MSI in patients with locally problematic advanced tumors might change treatment strategy and treatment aim in this setting, from a purely palliative approach to a quasi-curative paradigm. Keywords:  Microsatellite instability, Radiosensitivity, Prostate cancer Introduction Microsatellite instability (MSI) is characterized by mutations in repetitive DNA sequence tracts, as a consequence of an insufficient DNA mismatch repair system. Deficient DNA mismatch repair (dMMR) results from bi-allelic mutational inactivation or epigenetic silencing of any of the genes in the MMR pathway. Consequently, MSI status is used as a biomarker indicative of dMMR. MSI has been most closely studied in colorectal cancers (CRC), where it is present in up to 15–20% of cases *Correspondence: [email protected] 1 Radiotherapy Unit, Oncology and Hematology Department, University Hospital of Modena, Modena, Italy Full list of author information is available at the end of the article

[1]. However many other type of cancer showed MSI, like ovarian, endometrial and gastric cancer [2]. Several studies have reported MMR protein loss and MSI also in prostate cancer (PC), especially in advanced stages (APC). The prevalence of MSI-H/dMMR in PC, however, is still unclear, with frequencies ranging from 1.2% to 12.0% in previous reports [3]. MSI appears to be influencing cancer radiosensitivity, first reported in particular for MSI CRC [4], but still not clearly observed across other histologies. There is accumulating evidence to suggest that DNA MMR proteins may influence and/or are directly involved in the DNA