Prognostic factors for relapse in patients with clinical stage I testicular seminoma: A nationwide, population-based cohort study.
Thomas WagnerBirgitte Grønkær ToftJakob LauritsenMikkel BandakIb Jarle ChristensenBirte EngvadMichael Kreiberg JessenMads AgerbækLars DysagerJosephine RosenvildeDaniel M. BerneyGedske Daugaard
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5041 Background: Approximately 20% of patients with clinical stage I testicular seminoma will relapse after orchiectomy. No robust prognostic factors for relapse exist which challenges risk assessment and counselling for patients. Previous studies have been hampered by selection bias and variable pathology reporting that limit interpretation and generalization of results. We therefore assessed prognostic factors for relapse in a large unselected nationwide population-based setting with centralized pathology review. Methods: Patients with clinical stage I seminoma diagnosed in Denmark between 2013 and 2018 were identified in the prospective Danish Testicular Cancer database. By linkage to the Danish National Pathology Registry, microscopic slides from the orchiectomy specimens were retrieved and reviewed blinded to the clinical outcome. Clinical data were obtained from medical records with follow-up until July 2022. The association between prespecified clinical and histopathological prognostic factors and relapse were assessed by use of Cox regression analysis. Potential prognostic factors included age, pre-orchiectomy values of β-human chorionic gonadotropin (β-hCG) and lactate dehydrogenase (LDH), tumor size, tumor multifocality, tumor necrosis, lymphovascular invasion, pagetoid rete involvement, and invasion of rete testis, hilar soft tissue, epididymis, spermatic cord, tunica albuginea, and tunica vaginalis. Results: In total, 924 patients were included. During a median follow-up of 6.3 years, 148 (16%) patients relapsed. Invasion of the testicular hilum (rete testis and hilar soft tissue), lymphovascular invasion, and elevated pre-orchiectomy levels of β-hCG and LDH were independent predictors of relapse. The estimated 5-year risk of relapse ranged from 6% in patients with no risk factors, to 64% in patients with all four risk factors with tumor extension into the hilar soft tissue of the testicular hilum. After internal model validation, the model had an overall concordance statistic of 0.70. Conclusions: The provided prognostic factors allow a long-awaited opportunity to make more informed treatment decisions about post-orchiectomy management in patients with clinical stage I seminoma. These should replace current risk factors in guidelines and be used in future studies investigating risk-adapted follow-up and treatment strategies. [Table: see text]Keywords:
Rete testis
Orchiectomy
Lymphovascular invasion
To report the long-term outcome of surveillance for stage I seminoma at a single institution in Japan.A retrospective review of medical records of 64 patients who underwent orchiectomy between January 1982 and December 2005 was carried out. All of them were managed by surveillance for stage I seminoma.Median follow-up time was 123.8 months. Of the 64 patients, seven developed relapse. Four relapses occurred within the first year after orchiectomy, but three occurred over 4 years after orchiectomy. The actuarial relapse-free rates at 5, 10, and 15 years were 92.1%, 90.0%, and 86.0%, respectively. All patients received salvage chemotherapy at relapse. Four of these seven patients were alive without evidence of disease. One patient died of seminoma and one was alive with this disease. The remaining one patient died of leukemia without secondary relapse of seminoma. T classification was a statistically significant (P = 0.028) risk factor for relapse on univariate analysis. In T1 patients, relapse-free rates at 5, 10, and 15 years were all 97.1%, whereas in T2/T3 patients the corresponding relapse-free rates were 86.4%, 82.1%, and 71.8%, respectively.The relapse-free rate in the present study was similar to previous reports. Late relapse should be considered during surveillance.
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Testicular cancer represents approximately 1% of all cancers diagnosed in males. The prevalence of bilateral testicular germ cell tumor cases varies from 1% to 5%. Intratubular germ cell neoplasia (ITGCN) is a precursor for almost all testicular germ cell tumors (TGCT) and is one of the highest risks of developing contralateral testicular cancer. The radical orchiectomy is still preferred for the treatment of testicular cancer. However, in some cases like solitary testis, bilateral cancer or if the tumor size is under 30% percent of the testicular extent, organ-sparing surgery can be an option. There are just a few published reports of metachronous contralateral testicular cancer, developed after orchiectomy with the histopathology of the intratubular germ cell neoplasia.
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Summary— Twenty‐six of approximately 1300 patients (1.9%) with unilateral testicular cancer developed a second primary germ cell cancer (seminoma 18; non‐seminoma 8). Patients with previous seminoma had a significantly higher risk of developing a new seminoma than those with a previous non‐seminoma. The diagnosis of second primary was made within 3 years of the first diagnosis in only 50% of the patients. In patients with a history of undescended and/or atrophic testes the interval significantly decreased between the diagnosis of the two testicular cancers. The prognosis of bilateral testicular cancer is generally good. Patients in whom the second testicular cancer is at clinical stage I (no metastases) at diagnosis can safely be observed without further treatment after orchiectomy. A patient with unilateral testicular cancer should be informed of the increased risk of developing a second primary germ cell tumour and should be encouraged to perform regular examination of the remaining testis. The need for life‐long follow‐up visits for patients with testicular cancer is questionable.
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Incidental detection of urogenital tumors has increased in recent decades owing to the greater use of ultrasonography and cross-sectional imaging. For patients with low-risk prostate cancer or small renal masses, active surveillance represents a valid treatment option. Similarly, for men with small testicular masses <10 mm, active surveillance has been discussed as an alternative to surgery, although little is known regarding the behavior of small testicular germ cell tumors (GCTs). In the Swiss Austrian German Testicular Cancer Cohort Study we identified 849 patients (546 seminoma, 303 nonseminoma) treated with radical inguinal orchiectomy for GCT with a median tumor diameter of 35 mm. A tumor diameter <10 mm was observed in 25 patients (13 seminoma, 12 nonseminoma). Of these, five patients (20%) presented with primary metastatic disease, all of whom had elevated tumor markers and nonseminomatous GCTs. Two patients (8%) with initially localized disease (1 seminoma, 1 nonseminoma) and without elevated tumor markers experienced relapse at 4 mo (nonseminoma) and 14 mo (seminoma) after orchiectomy, despite the fact that the latter had received adjuvant chemotherapy. These findings highlight the metastatic potential of small testicular GCTs and raise the question of whether active surveillance for small testicular masses is safe.
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Recurrent seminoma in the contralateral testicle after orchiectomy is a rare occurrence, with a reported incidence less than 5%. Testicular ultrasound was performed on a 36-year-old man with a clinical history of previous left orchiectomy for testicular neoplasm. Recurrent seminoma was the pathologic diagnosis in the remaining right testicle. This can be a difficult diagnosis to make using ultrasound due to previous orchiectomy.
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Testicular cancer is an uncommon cancer and of the estimated 7,920 new cases diagnosed in 2013, 370 will result in death. It is most common in young or middle-aged males and rarely occurs in older males. Ninety-five percent of these cancers originate in sperm-producing germ cells. There are two different subclasses of testicular cancer, namely nonseminoma and seminoma. Nonseminoma testicular cancers, such as embryonal carcinomas, yolk sac carcinomas, choriocarcinomas, and teratomas usually affect younger-aged males, whereas seminoma testicular cancers often occur in older males. It is unclear why testicular cancer is rare in older men, but because it is so unusual in older men, the diagnosis is frequently overlooked when presenting with signs suggestive of testicular carcinoma. A 75-year-old male recently presented with signs and symptoms classically descriptive of testicular cancer. The patient was treated with an orchiectomy. The pathologic evaluation of the excised testicle confirmed the diagnosis of a seminoma. This report is an account of the case from initial visit to treatment and a discussion of its relevance.
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Late recurrence of stage I testicular seminoma is rare. We herein report a case of retroperitoneal lymph node recurrence of testicular seminoma 6 years after high orchiectomy. A 39-year-old man had a left high orchiectomy for stage I testicular tumor in November 1997. Histopathological findings revealed seminoma (pT3). In 2003, follow up computed tomography showed retroperitoneal lymph nodes swelling. Serum tumor markers had been normal since 1997. Retroperitoneal lymph nodes were dissected in April 2004. Histopathological findings were recurrence of seminoma.
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Surveillance of selected patients with clinical stage I germ-cell tumours of the testis is a safe alternative to further immediate treatment. Cure rates appear to be equivalent and are nearly 100%. The morbidity of prophylactic therapy can be avoided in up to 85% of seminoma and 70% of non-seminoma patients who will not progress after orchiectomy alone.
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