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      Clinical implications of the American Joint Committee on Cancer (AJCC) 8th edition update in seminoma pT1 subclassification

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          Abstract

          Background

          Seminoma accounts for 30–50% of testicular germ cell tumors (TGCT)—the most common solid malignancy in men aged 15–35 years. The American Joint Committee on Cancer (AJCC) 8th edition (2018) created the subclassifications pT1a (tumor size < 3 cm) and pT1b (≥ 3 cm), despite not being universally recognized. Rete testis invasion (RTI) and tumor size > 4 cm are considered features associated with a higher recurrence risk, but not formally used for staging. The authors propose further understanding the subclassification’s potential impact in clinical practice, by summarizing current evidence and reviewing clinical cases in their institutions.

          Methods

          All consecutive cases of seminoma stage I, pT1 treated in two institutions between January 2005 and December 2016 were included. Clinical data were retrieved, and variables were analyzed using SPSS. Relevant literature on the topic was reviewed.

          Results

          Seminoma pT1 was identified in 58 patients. By using newly AJCC criteria, 29 (50%) would have been staged as pT1a and 29 (50%) pT1b. Median age at diagnosis was similar (33 in pT1a vs 32 in pT1b). Median follow-up time 5.8 years. Almost half (45%) of pT1b patients had a tumor size < 4 cm. The majority of either pT1a or pT1b were treated with chemotherapy or radiotherapy, reflecting more intensive approaches in the past. Three retroperitoneal recurrences were recorded (two in pT1a, one in pT1b, all under surveillance protocol); no deaths occurred. RTI and extensive necrosis (EN) were associated with pT1b ( P <  0.0001 and P = 0.023, respectively), known adverse biological features.

          Conclusions

          In our population, the exploratory analysis of the newly created AJCC criteria showed no significant difference in recurrence or death, although pT1b was associated with adverse biomarkers, such as RTI and EN, but its clinical relevance remains incompletely understood. Our results confirm an excellent prognosis, regardless of subcategorization, thus a larger population and a longer follow-up time are needed to understand prospectively the impact of the recently updated criteria. We would recommend using the latest AJCC staging system, although the individual risk of relapse, long-term toxicities and patient preferences should be taken into account when considering surveillance or active treatment adjuvant options.

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          Most cited references13

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          ESMO Consensus Conference on testicular germ cell cancer: diagnosis, treatment and follow-up

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            Prognostic factors for relapse in stage I seminoma managed by surveillance: a pooled analysis.

            Several management options are available to patients with stage I seminoma, including adjuvant radiotherapy, surveillance, and adjuvant chemotherapy. We performed a pooled analysis of patients from the four largest surveillance studies to better delineate prognostic factors associated with disease progression. Individual patient data were obtained from each center (Princess Margaret Hospital, Danish Testicular Cancer Study Group, Royal Marsden Hospital, and Royal London Hospital) for 638 patients. Tumor characteristics (size, histologic subtype, invasion of rete testis, and tumor invasion into small vessels [SVI]) as well as age at diagnosis were analyzed for prognostic importance for relapse. With a median follow-up of 7.0 years (range, 0.02 to 17.5 years), 121 relapses were observed for an actuarial 5-year relapse-free rate (RFR) of 82.3%. On univariate analysis, tumor size (RFR: 4 cm, 76%; P =.003), rete testis invasion (RFR: 86% [absent] v 77% [present], P =.003), and the presence of SVI (RFR: 86% [absent] v 77% [present], P =.038) were predictive of relapse. On multivariate analysis, tumor size ( 4 cm, hazard ratio 2.0; 95% confidence interval [CI], 1.3 to 3.2) and invasion of the rete testis (hazard ratio 1.7; 95% CI, 1.1 to 2.6) remained as important predictors for relapse. We have identified size of primary tumor and rete testis invasion as important prognostic factors for relapse in patients with stage I seminoma managed with surveillance. This information will allow patients and clinicians to choose management based on a more accurate assessment of an individual patient's risk of relapse. In addition, it will allow clinicians to tailor follow-up protocols based on risk of occult disease.
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              Evaluation of a prognostic model for risk of relapse in stage I seminoma surveillance

              A prognostic model for relapse risk in stage I seminoma managed by surveillance after orchiectomy has been developed but has not been independently validated. Individual data on 685 stage I seminoma surveillance patients managed between 1998 and 2005 at three cancer centers were retrospectively analyzed. Variables including age and pathology of the primary tumor: small vessel invasion, tumor size, and invasion of rete testis were analyzed. Specifically median tumor size and rete testis invasion was tested to evaluate the performance of the published model. Median follow-up was 3.85 years (0.1–10.29), 88 patients relapsed and 5-year relapse-free rate was 85%. In univariate analysis, median tumor size (<3 cm vs. ≥3 cm) was associated with increased risk of relapse but rete testis invasion was not, nor was age and small vessel invasion. In multivariable analysis, tumor size above median (cutpoint of 3 cm) was a predictor for relapse, HR 1.87 (95% CI 1.15, 3.06), whereas rete testis invasion HR 1.36, (95% CI 0.81, 2.28) was not statistically significant. The 3-year relapse risk based on the primary tumor size alone increased from 9% for 1 cm primary tumor to 26% for 8 cm tumor. A clinically useful, highly discriminating prognostic model remains elusive in stage I seminoma surveillance as we were unable to validate the previously developed model. However, primary tumor size retained prognostic importance and a scale of relapse risk based on the unit increment of tumor size was developed to help guide patients and clinicians in decision making.
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                Author and article information

                Contributors
                mario.fontes.sousa@cuf.pt , mario_fontes_sousa@hotmail.com
                Journal
                BMC Urol
                BMC Urol
                BMC Urology
                BioMed Central (London )
                1471-2490
                20 August 2020
                20 August 2020
                2020
                : 20
                : 127
                Affiliations
                [1 ]Serviço de Oncologia Médica, Centro Hospitalar Lisboa Ocidental, Estr. Forte do Alto Duque, 1449-005 Lisbon, Portugal
                [2 ]GRID grid.5808.5, ISNI 0000 0001 1503 7226, Serviço de Anatomia Patológica, Instituto Português de Oncologia do Porto, Porto and Grupo de Epigenética e Biologia do Cancro (GEBC), Centro de Investigação do Instituto Português de Oncologia do Porto (CI-IPOP) e Instituto de Ciências Biomédicas Abel Salazar, , Universidade do Porto (ICBAS-UP), ; Porto, Portugal
                [3 ]GRID grid.413151.3, ISNI 0000 0004 0574 5060, Serviço de Oncologia Médica, , Unidade Local de Saúde de Matosinhos (Hospital Pedro Hispano), ; Porto, Portugal
                [4 ]Serviço de Anatomia Patológica, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal
                [5 ]GRID grid.435544.7, Serviço de Oncologia Médica, Instituto Português de Oncologia do Porto, ; Porto, Portugal
                Author information
                http://orcid.org/0000-0003-0337-3251
                Article
                682
                10.1186/s12894-020-00682-7
                7439661
                32819326
                d85bd168-b1b3-4ad9-b663-f209efd7c052
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 14 February 2020
                : 22 July 2020
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Urology
                germ cell tumors,seminoma,cancer staging,ajcc,rete testis,biomarkers
                Urology
                germ cell tumors, seminoma, cancer staging, ajcc, rete testis, biomarkers

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