Real-World Application of Pre-Orchiectomy miR-371a-3p Test in Testicular Germ Cell Tumor Management

Badia, Rohit R; Abe, Dreaux; Wong, Daniel; Singla, Nirmish; Savelyeva, Anna; Chertack, Nathan; Woldu, Solomon L.; Lotan, Yair; Mauck, Ryan; Ouyang, Deqin; Meng, Xiaosong; Lewis, Cheryl; Majmudar, Kuntal; Jia, Liwei; Kapur, Payal; Xu, Lin; Frazier, A. Lindsay; Margulis, Vitaly; Strand, Douglas W.; Murray, Matthew J.; Amatruda, James F.; Lafin, John T.; Bagrodia, Aditya

doi:10.1097/ju.0000000000001337

Cited by 40 publications

(33 citation statements)

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“…The management of these lesions is evolving, with some centers offering active surveillance with serial ultrasound examinations as an initial approach 6 . Moreover, recent studies are beginning to explore the use of ultra‐sensitive mRNA biomarkers to guide more accurate diagnosis, further questioning our current management pathways 7 …”

Section: Introductionmentioning

confidence: 99%

Outcomes of organ‐sparing surgery for adult testicular tumors: A systematic review of the literature

et al. 2021

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Objective To perform a systematic review on the effects of testicular sparing surgery (TSS) on the oncological, functional, and hormonal outcomes of adults with testicular tumors. Methods A literature search was performed after PROSPERO registration (CRD42020200842) and reported in compliance with Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) methods. We conducted a systematic search of Medline (Ovid), Embase, Cochrane CENTRAL, CINAHL, Scopus, Web of Science, ClinicalTrials.gov, and the WHO/ICTRP from inception to November 20, 2020. Manuscripts and published abstracts were included if they involved testis‐sparing surgery (TSS) and contained data on any outcomes related to fertility, hormonal parameters, or oncological control, or if they evaluated surgical technique. Results Our initial search yielded 3,370 manuscripts, with 269 of these screened for full‐text eligibility. After our exclusion criteria were applied, 32 studies were included in the final analysis. Oncological outcomes were obtained from 12 studies (average follow‐up 57.8 months), functional data from 26 studies (average follow‐up 49.6 months), fertility information from 10 studies (average follow‐up 55.8 months), and data on nonpalpable tumors from 11 studies (average follow‐up 32.1 months). Oncological control appears to be excellent in studies that reported these outcomes. Presence of germ cell neoplasia in situ was controlled with adjuvant radiation in nearly all cases. Functional outcomes are also promising, as development of primary and compensated hypogonadism was rare. Semen parameters are poor preoperatively among men with benign and malignant testis tumors, with occasional decline after TSS. Frozen section analysis at the time of surgery appears to be very reliable, and the majority of nonpalpable tumors appear to be benign. Conclusions TSS is a safe and efficacious technique with regards to oncological control and postoperative hormonal function based on retrospective, noncontrolled studies. TSS avoids unnecessary removal of benign testicular tissue, and should be given serious consideration in cases of nonpalpable, small tumors under 2 cm. In cases of malignancy, TSS can safely avoid anorchia in men with bilateral tumors and in men with solitary testicles. The use of the operating microscope, while theoretically promising, does not necessarily lead to better outcomes, however data are limited.

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Section: Introductionmentioning

confidence: 99%

Outcomes of organ‐sparing surgery for adult testicular tumors: A systematic review of the literature

et al. 2021

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“…The use of circulating miR-371a-3p was analyzed as a marker for malignant germ cell tumor management in TGCT patients (range, 26–40 years) prior to orchiectomy [ 85 ]. Performance characteristics of serum miR-371a-3p were compared with predictable markers, including α-fetoprotein, β-human chorionic gonadotropin, and lactate dehydrogenase.…”

Section: Molecular Biologymentioning

confidence: 99%

“…Performance characteristics of serum miR-371a-3p were compared with predictable markers, including α-fetoprotein, β-human chorionic gonadotropin, and lactate dehydrogenase. The miR-371a-3p test showed a specificity of 100%, sensitivity of 93%, and AUC of 0.978 [ 85 ]. These results confirm the previously published studies and suggest the effectiveness of a positive miR-371a-3p test post-chemotherapy.…”

Section: Molecular Biologymentioning

confidence: 99%

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Molecular Biology of Pediatric and Adult Male Germ Cell Tumors

Pinto

Cárcano

Vieira

et al. 2021

Cancers

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Cancer is a leading cause of death by disease in children and the second most prevalent of all causes in adults. Testicular germ cell tumors (TGCTs) make up 0.5% of pediatric malignancies, 14% of adolescent malignancies, and are the most common of malignancies in young adult men. Although the biology and clinical presentation of adult TGCTs share a significant overlap with those of the pediatric group, molecular evidence suggests that TGCTs in young children likely represent a distinct group compared to older adolescents and adults. The rarity of this cancer among pediatric ages is consistent with our current understanding, and few studies have analyzed and compared the molecular basis in childhood and adult cancers. Here, we review the major similarities and differences in cancer genetics, cytogenetics, epigenetics, and chemotherapy resistance between pediatric and adult TGCTs. Understanding the biological and molecular processes underlying TGCTs may help improve patient outcomes, and fuel further investigation and clinical research in childhood and adult TGCTs.

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“…Even small GCTs of less than 10 mm of size can generate elevated M371 serum levels [ 17 , 18 ]. Based on the high sensitivity of > 90%, it has been speculated that this marker would also be informative in patients harbouring small volume occult metastases [ 19 , 20 ]. A prospective study had shown that M371 serum levels dropped after orchiectomy in 92% of CS1 patients, but around 20% of them had still elevated M371 levels postoperatively [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Associations of serum levels of microRNA-371a-3p (M371) with risk factors for progression in nonseminomatous testicular germ cell tumours clinical stage 1

Dieckmann

Dumlupinar

Radtke³

et al. 2021

World J Urol

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Purpose Lymphovascular invasion (LV1) and presence of > 50% embryonal carcinoma (> 50% EC) represent risk factors for progression in patients with clinical stage 1 (CS1) nonseminomatous (NS) testicular germ cell tumours. As serum levels of microRNA-371a-3p (M371) are capable of detecting small amounts of GCT, we evaluated if LV1 and > 50% EC are associated with M371 levels. Methods M371 serum levels were measured postoperatively in 153 NS CS1 patients and both pre- and postoperatively in 131 patients. We registered the following factors: age, tumour size, LV status, > 50% EC, teratoma in primary, preoperative elevation of classical tumour markers. M371 expression was compared among subgroups. The ability of M371 to predict LV1 was calculated by receiver operating characteristics (ROC) curves. Multiple regression analysis was used to look for associations of M371 levels with other factors. Results Postoperatively elevated M371 levels were found in 29.4% of the patients, but were neither associated with LV status nor with > 50% EC. Likewise, relative decrease of M371 was not associated. ROC analysis of postoperative M371 levels revealed an AUC of 0.5 for the ability to predict LV1 while preoperative M371 had an AUC of 0.732. Multiple regression analysis revealed significant associations of preoperative M371 levels with LV status (p = 0.003), tumour size (p = 0.001), > 50% EC (p = 0.004), and teratoma component (p = 0.045). Conclusion Postoperatively elevated M371 levels are not associated with risk factors for progression in NS CS1 patients. However, the significant association of preoperative M371 expression with LV1 deserves further evaluation.

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Real-World Application of Pre-Orchiectomy miR-371a-3p Test in Testicular Germ Cell Tumor Management

Cited by 40 publications

References 0 publications

Outcomes of organ‐sparing surgery for adult testicular tumors: A systematic review of the literature

Outcomes of organ‐sparing surgery for adult testicular tumors: A systematic review of the literature

Molecular Biology of Pediatric and Adult Male Germ Cell Tumors

Associations of serum levels of microRNA-371a-3p (M371) with risk factors for progression in nonseminomatous testicular germ cell tumours clinical stage 1

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