Combined DNA repair defects in testicular metastasis from prostate cancer sensitize to immune checkpoint blockade
Abstract. Testicular metastasis in prostate cancer is uncommon and may be a culprit of widespread disease which portends a worse prognosis. Little is known about the molecular biology of metastases to the testicles and whether there is any role for targeted therapeutics. Here we report a case of pro...
| Main Author: | |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Health
2021-12-01
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| Series: | Current Urology |
| Online Access: | http://journals.lww.com/10.1097/CU9.0000000000000039 |
| _version_ | 1828751674127155200 |
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| author | Panagiotis J. Vlachostergios |
| author_facet | Panagiotis J. Vlachostergios |
| author_sort | Panagiotis J. Vlachostergios |
| collection | DOAJ |
| description | Abstract. Testicular metastasis in prostate cancer is uncommon and may be a culprit of widespread disease which portends a worse prognosis. Little is known about the molecular biology of metastases to the testicles and whether there is any role for targeted therapeutics. Here we report a case of prostate cancer recurring with testicular and lung metastases. Targeted sequencing of the patient's left testicular tumor after orchiectomy disclosed inactivating mutations in the CDK12 and ARID1A genes, and MSH2 and MSH6 loss resulting in high microsatellite instability and high tumor mutational burden. The patient experienced a complete radiographic and prostate-specific antigen response at 12 weeks of PD-1 immune checkpoint blockade with pembrolizumab and continues uneventfully on treatment. Molecular characterization of this rare phenotypic subtype of prostate cancer in larger studies may help deliver precision therapies with the potential to improve outcomes. |
| first_indexed | 2024-12-10T20:56:59Z |
| format | Article |
| id | doaj.art-84a596c565a74ab7b94b7b8dcff13a42 |
| institution | Directory Open Access Journal |
| issn | 1661-7649 1661-7657 |
| language | English |
| last_indexed | 2024-12-10T20:56:59Z |
| publishDate | 2021-12-01 |
| publisher | Wolters Kluwer Health |
| record_format | Article |
| series | Current Urology |
| spelling | doaj.art-84a596c565a74ab7b94b7b8dcff13a422022-12-22T01:33:56ZengWolters Kluwer HealthCurrent Urology1661-76491661-76572021-12-0115423423710.1097/CU9.0000000000000039202112000-00011Combined DNA repair defects in testicular metastasis from prostate cancer sensitize to immune checkpoint blockadePanagiotis J. Vlachostergios0Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, USAAbstract. Testicular metastasis in prostate cancer is uncommon and may be a culprit of widespread disease which portends a worse prognosis. Little is known about the molecular biology of metastases to the testicles and whether there is any role for targeted therapeutics. Here we report a case of prostate cancer recurring with testicular and lung metastases. Targeted sequencing of the patient's left testicular tumor after orchiectomy disclosed inactivating mutations in the CDK12 and ARID1A genes, and MSH2 and MSH6 loss resulting in high microsatellite instability and high tumor mutational burden. The patient experienced a complete radiographic and prostate-specific antigen response at 12 weeks of PD-1 immune checkpoint blockade with pembrolizumab and continues uneventfully on treatment. Molecular characterization of this rare phenotypic subtype of prostate cancer in larger studies may help deliver precision therapies with the potential to improve outcomes.http://journals.lww.com/10.1097/CU9.0000000000000039 |
| spellingShingle | Panagiotis J. Vlachostergios Combined DNA repair defects in testicular metastasis from prostate cancer sensitize to immune checkpoint blockade Current Urology |
| title | Combined DNA repair defects in testicular metastasis from prostate cancer sensitize to immune checkpoint blockade |
| title_full | Combined DNA repair defects in testicular metastasis from prostate cancer sensitize to immune checkpoint blockade |
| title_fullStr | Combined DNA repair defects in testicular metastasis from prostate cancer sensitize to immune checkpoint blockade |
| title_full_unstemmed | Combined DNA repair defects in testicular metastasis from prostate cancer sensitize to immune checkpoint blockade |
| title_short | Combined DNA repair defects in testicular metastasis from prostate cancer sensitize to immune checkpoint blockade |
| title_sort | combined dna repair defects in testicular metastasis from prostate cancer sensitize to immune checkpoint blockade |
| url | http://journals.lww.com/10.1097/CU9.0000000000000039 |
| work_keys_str_mv | AT panagiotisjvlachostergios combineddnarepairdefectsintesticularmetastasisfromprostatecancersensitizetoimmunecheckpointblockade |