Testicular tumors in men aged 60 years or older undergoing orchiectomy

Introduction

Testicular tumors are relatively rare particularly in elderly individuals, while the tumors in older patients are often dissimilar in histopathology and behavior from those routinely encountered in younger patients (1,2). Specifically, germ cell tumors occur mostly in the young population (e.g., <50 years), whereas lymphomas and spermatocytic tumor, as well as sarcomas in the paratesticular region, are often seen in aged men (1-5).

In recent decades, there appears to have been a considerable increase in the incidence of testicular tumors in the elderly (5-9), which underlines the need for knowledge about clinical and pathological features in this age group. Nevertheless, to the best of our knowledge, few studies have systematically characterized these tumors in the elderly. Further investigation is thus indicated regarding the biological and clinical peculiarities of testicular tumors in older men and the optimization of treatment strategies for this population. The present study focuses on germ cell tumors or sex cord-stromal tumors of the testis in men aged 60 years or older by presenting their clinicopathologic features and oncologic outcomes. We present this article in accordance with the STROBE reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-261/rc).

Methods

Study population

We assessed consecutive patients undergoing orchiectomy for testicular tumors at the University of Rochester Medical Center between 2006 and 2022. From our surgical pathology database, we identified a total of 343 and 46 men at the ages of <60 years and ≥60 years, respectively, who met the inclusion criteria after excluding cases undergoing orchiectomy for non-neoplastic conditions or non-testicular tumors. This study was performed in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Review Board at the University of Rochester Medical Center (No. 00007950), and informed consent for this retrospective analysis was waived.

Data extraction

Data collected included patient demographics and tumor characteristics, such as size, focality, laterality, and histopathology, as well as subsequent treatment, including radiotherapy and chemotherapy, and clinical outcome data, extracted from the surgical pathology database and/or the hospital’s integrated electronic health record system. All orchiectomy specimens were subjected to uniform histopathological examinations, and the diagnoses of non-lymphomas and lymphomas were originally made by groups of genitourinary pathologists and hematopathologists, respectively, at the University of Rochester Medical Center. These were then re-classified, if necessary, according to the current World Health Organization classification (10). In addition, germ cell tumors were staged according to the current American Joint Committee on Cancer/Union for International Cancer Control tumor-node-metastasis (TNM) staging system (11). Serial evaluations of serum markers, such as α-fetoprotein (AFP), human chorionic gonadotropin (hCG), and lactate dehydrogenase, were also performed in patients with germ cell tumor.

Statistical analysis

Student’s t-test and Fisher’s exact test (two-tailed) were used to compare numerical and categorized data, respectively. Time-to-event estimates of recurrence-free survival were calculated by the Kaplan-Meier method and compared by the log-rank test, using Prism version 10.4.1 (GraphPad Software Inc., San Diego, CA, USA). In addition, the Cox proportional hazards model was used to determine statistical significance of prognostic factors in a multivariable setting, using EZR software (R version 4.0.2; The R Foundation for Statistical Computing, Vienna, Austria). A P value of less than 0.05 was considered to be statistically significant.

Results

We retrospectively examined 46 orchiectomies in men aged 60 years or older. In addition to diffuse large B-cell lymphoma (n=15, 33%) and spermatocytic tumor (formerly called spermatocytic seminoma) (n=3, 7%) that were known to be predominantly seen in elderly patients (12,13), histopathological diagnoses included pure seminoma (n=15, 33%), mixed germ cell tumor (n=4, 9%), Leydig cell tumor (n=4, 9%), Sertoli cell tumor (n=2, 4%), epidermoid cyst (n=1, 2%), metastatic renal cell carcinoma (n=1, 2%), and plasmacytoma (n=1, 2%) (Table 1).

Germ cell tumor

Table 2 summarizes the clinicopathologic features of individual cases with seminoma or mixed germ cell tumor. Interestingly, 11 (58%) of these cases were from 2018–2022, whereas 2 (11%) and 6 (32%) were diagnosed in 2013–2017 and 2008–2012, respectively (i.e., no cases from 2006–2007). Surgical margins were negative for tumor in all cases.

Pure seminoma represented the most frequent tumor type in our cohort. The median age of the patients was 63 years with a range from 60 to 78 years, and 9 (60%) of 15 were thus under 65 years. Serum tumor markers were mostly normal, while no syncytiotrophoblast cells were histologically detected even in 2 cases where hCG was mildly elevated (i.e., 10–12 mIU/mL). Most (n=13; 87%) were unifocal, and the average and mean sizes of the tumors (dominant nodules in multifocal cases) were 3.9 cm and 4.8 cm, respectively, with a range of 2.0–7.6 cm. These tumors were staged as pT1 (n=9, 60%; 2 pT1a and 7 pT1b), pT2 (n=5, 33%), or pT3 (n=1, 7%). The pT3 case showed abdominal and pelvic lymphadenopathy on imaging studies (cN2). Two (22%) of 9 pT1 cases subsequently underwent prophylactic radiotherapy, whereas 2 (40%) of 5 pT2 cases had chemotherapy. There were no recorded relapses in any of these pT1 or pT2 patients during the follow-up (mean: 83.8 months; median: 82 months; range, 10–174 months). In addition, the pT3/cN2 case achieved clinically complete response following adjuvant chemotherapy (etoposide + cisplatin × 4 cycles) and had no relapse 50 months after orchiectomy.

Mixed germ cell tumors were found in 4 patients (9%) where seminoma (n=3), embryonal carcinoma (n=3), yolk sac tumor (n=3), choriocarcinoma (n=1), and teratoma (n=3) components were present. Their median age was 61.5 years (range, 60–64 years). AFP was considerably elevated (i.e., 166–874 ng/mL) in 3 cases with yolk sac tumor component, whereas hCG was high (i.e., 2,267 mIU/mL) in a case with choriocarcinoma component. Their tumor size (3 unifocal and 1 multifocal) ranged 1.8–6.2 cm (mean: 4.8 cm). These included 3 pT1 and 1 pT2 diseases clinically with no metastasis at the time of surgery. However, 2 of them were found to have lymph node metastasis 13 and 49 months after orchiectomy, and lymph node dissection without adjuvant treatment identified embryonal carcinoma and seminoma, respectively. All of these 4 mixed germ cell tumor cases were alive without disease at the last follow-up (mean: 78.4 months; median: 63 months; range, 28–157 months after orchiectomy).

Sex cord-stromal tumor

Table 3 summarizes the clinicopathologic features of individual cases with sex cord-stromal tumor.

There were 4 cases of Leydig cell tumor in ages of 60, 66, 67, and 93 years. These tumors were relatively small with sizes of 0.5–2.0 cm in greatest dimension and were confined to the testis with no rete testis invasion.

There were 2 cases of Sertoli cell tumor in ages of 73 and 76 years. These tumors were also relatively small with sizes of 0.7–1.2 cm in greatest dimension and were confined to the testis with no rete testis invasion.

Histological features suggestive of malignancy, such as cytologic atypia, frequent mitoses, necrosis, lymphovascular invasion, and extratesticular spread (14-16), were not seen in any of these 6 cases with sex cord-stromal tumor. After 12–141 months (median: 42 months) of follow-up, no patients developed recurrent or metastatic disease.

Comparisons with orchiectomy cases at <60 years of age

We then compared the incidence of each tumor type (Table 4) and the prognosis of germ cell tumors (Figure 1) between the elderly and younger groups. From our database search, we identified 343 men who had undergone orchiectomy for testicular tumors at <60 years of age.

Figure 1 Kaplan-Meier curves for recurrence-free survival in patients with seminoma (A), mixed germ cell tumor (B), or either mixed germ cell tumor or non-seminomatous germ cell tumor (C) who were aged 60 years or older vs. younger than 60 years at orchiectomy. Comparisons between two groups were made by the log-rank test.

As expected, hematological malignancy (35% vs. 2%; P<0.001) and spermatocytic tumor (7% vs. 1%; P=0.02) were significantly more often seen in ≥60-year-old patients than in <60-year-old patients. By contrast, mixed germ cell tumor (29% vs. 9%; P=0.004), non-seminomatous germ cell tumor including 29 cases of embryonal carcinoma and 2 cases of teratoma (9% vs. 0%; P=0.04), or either (38% vs. 9%; P<0.001) was significantly more common in the younger group. There were no significant differences in the incidence of seminoma (33% vs. 43%; P=0.20), sex cord-stromal tumor (13% vs. 6%; P=0.12), epidermoid cyst or dermoid cyst (2% vs. 5%; P=0.62), or other tumors between the elderly and younger groups. In addition, pT stage and tumor size were not significantly different between the two groups with seminoma or mixed germ cell tumor/non-seminomatous tumor.

Univariate analysis was performed to assess the impact of age group on oncologic outcomes. In seminoma patients, age was not strongly associated with the risk of recurrence (P=0.22), although none of ≥60-year-old patients had recurrent disease (Figure 1A). However, in those with mixed germ cell tumor (P=0.0498; Figure 1B) or either mixed germ cell tumor or non-seminomatous germ cell tumor (P=0.049; Figure 1C), the older group had a significantly higher risk of recurrence, compared with <60-year-old patients. Multivariable analysis was further performed, using the Cox regression model, to determine if the older age was an independent predictor of postoperative recurrence. In patients with mixed germ cell tumor [hazard ratio (HR) 5.57, 95% confidence interval (CI): 1.18–26.4, P=0.03; Table 5] or either mixed germ cell tumor or non-seminomatous germ cell tumor (HR 5.88, 95% CI: 1.28–27.0, P=0.02; Table 6), ≥60 years showed a significantly higher risk of recurrence. Nonetheless, the presence of each germ cell tumor component or combinations of multiple components was not strongly associated with the risk of recurrence (data not shown).

Meanwhile, none of seminoma patients diagnosed at any age died of disease. Additionally, in those with mixed germ cell tumor, none (0%) of 4 ≥60-year-old patients versus 3 (3%) of 98 <60-year-old patients died of disease (P>0.99).

Discussion

We herein examined 46 men undergoing orchiectomy at the age of ≥60 years. The findings in the present study are crucial as they provide critical information about the characteristics and outcomes of germ cell tumors of the testis in aged males.

Consistent with the literature (5,17-20), pure classic seminoma was the most common subtype of germ cell tumor in our cohort of patients. No recurrences were observed in not only 14 cases of pT1 or pT2 disease with or without radiotherapy or chemotherapy, as prophylactic treatment after orchiectomy, but also a pT3cN2 patient undergoing standard adjuvant chemotherapy which achieved complete response.

In contrast, mixed germ cell tumors, as seen in 2 of our patients who developed lymph node metastasis, generally followed a more aggressive clinical course. This underlines the requirement of close follow-up after surgery, as well as more radical remedial strategies aiming at minimizing the risks for recurrence and metastasis. Indeed, a patient with no metastatic disease undergoing preventive chemotherapy immediately after orchiectomy had no disease recurrence or progression at the last follow-up. Moreover, following standard chemotherapy or retroperitoneal lymph node dissection alone, the 2 patients with relapse were alive with no disease at the last follow-up.

None of our cohort of patients with seminoma or mixed germ cell tumor diagnosed at ≥60 years of age, including those with postoperative recurrence, died of disease. Our findings in seminomas and mixed germ cell tumors indicate that testicular germ cell tumors even in the older patients with attendant medical comorbidities can be managed effectively with similar treatment modalities used in younger patients. However, it should be noted that testicular tumors may require age-specific considerations because some of elderly patients are unable to receive standard treatment (3,4,17-19,21,22). Consequently, the need for ongoing research on the optimal management of testicular tumors in elderly patients is emphasized once again. As evidenced by the studies (4,11,17-22), variable outcomes among the different tumor types highlight the need for more tailored treatment strategies, underlining the specific difficulties posed by this demographic group. Meanwhile, analysis of registry data from a large clinical trial involving 9,728 patients with metastatic non-seminomatous germ cell tumor treated with cisplatin- and etoposide-based first-line chemotherapy in at least 30 institutions in Europe, North America, and Australia indicated that the age was an independent prognosticator (HR 1.25, 95% CI: 1.15–1.36 per 10 years increase) (23). In line with these findings, comparative univariate analysis of postoperative oncologic outcomes in our cohorts revealed that ≥60-year-old patients with mixed germ cell tumor or either mixed germ cell tumor or non-seminomatous germ cell tumor had a significantly higher risk of disease recurrence after orchiectomy, compared with respective control patients aged <60 years. Moreover, multivariable analysis data indicated that the older age (i.e., ≥60 years) was found to be an independent predictor of postoperative recurrence. However, there was no significant difference in the rate of recurrence-free survival between our seminoma patients aged ≥60 vs. <60 years. Future studies should serve to define the risk factors associated with testicular tumors more accurately particularly in elderly patients and elucidate the role of individualized treatment strategies, novel treatments including targeted therapy, or combinations of treatments that might prove useful.

The current series of spermatocytic tumors, Leydig cell tumors, and Sertoli cell tumors all demonstrated no single recurrence or metastasis during the follow-up period, revealing the relatively indolent nature of these tumors among the elderly. The observations are consistent with the fact that orchiectomy alone is often curative (14-16), while in these older populations a less aggressive approach may be desirable. Additionally, it is noteworthy to mention that radical orchiectomy represents the standard treatment for all solid testicular masses but that the European Association of Urology guidelines recommend testis-sparing surgery in select cases with sex cord-stromal tumor (24). In this respect, intraoperative pathology consultation with frozen section assessment may be helpful for preventing unnecessary orchiectomy (25), although all 6 elderly patients in our cohort underwent radical orchiectomy without intraoperative pathology consultation.

Several limitations of this study need to be taken into consideration. First and foremost, this is a retrospective study from a single academic institution, and the design automatically places one at a significant disadvantage in relation to the control of confounding variables. Another limitation was that the surgical pathology database was first searched retrospectively, and some data might have been incomplete or biased. Moreover, detailed comorbidity information, which could have considerably influenced both treatment selection and patient outcome, was not available. In addition, the sample size in the elderly group was relatively small, especially for the rarer tumor types, which affects the generalizability of the findings. Although it would have potentially been interesting to examine the inclusion of lymphomas, particularly diffuse large B-cell lymphoma, this would reduce any in-depth evaluation of the subgroup of non-lymphoma tumors. Validation should thus be undertaken in larger patient cohorts in future studies. In particular, collaborative, multicenter studies could provide for larger analyses and definitive conclusions.

Conclusions

This study provides important insights into the clinicopathologic features and outcomes of germ cell tumors of the testis in elderly males. The results of this analysis showed that the bulk of the lesions is represented by seminomas in this patient population, and their long-term outcomes, after orchiectomy and appropriate adjuvant therapy, are excellent. Additionally, less common mixed germ cell tumors seem to be very well managed in older patients despite their potential comorbidities in our small group of patients, while demonstrating that older age was an independent risk factor of disease recurrence.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-261/rc

Data Sharing Statement: Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-261/dss

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-261/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-261/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was performed in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Review Board at the University of Rochester Medical Center (No. 00007950), and informed consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Al-Obaidy KI, Idrees MT. Testicular Tumors: A Contemporary Update on Morphologic, Immunohistochemical and Molecular Features. Adv Anat Pathol 2021;28:258-75. [Crossref] [PubMed]
2. Berney DM, Cree I, Rao V, et al. An introduction to the WHO 5th edition 2022 classification of testicular tumours. Histopathology 2022;81:459-66.
3. Gigantino V, La Mantia E, Franco R, et al. Testicular and testicular adnexa tumors in the elderly. Anticancer Drugs 2013;24:228-36. [Crossref] [PubMed]
4. Secondino S, Rosti G, Tralongo AC, et al. Testicular tumors in the "elderly" population. Front Oncol 2022;12:972151. [Crossref] [PubMed]
5. Ghazarian AA, Rusner C, Trabert B, et al. Testicular cancer among US men aged 50 years and older. Cancer Epidemiol 2018;55:68-72. [Crossref] [PubMed]
6. Shanmugalingam T, Soultati A, Chowdhury S, et al. Global incidence and outcome of testicular cancer. Clin Epidemiol 2013;5:417-27. [Crossref] [PubMed]
7. Le Cornet C, Lortet-Tieulent J, Forman D, et al. Testicular cancer incidence to rise by 25% by 2025 in Europe? Model-based predictions in 40 countries using population-based registry data. Eur J Cancer 2014;50:831-9. [Crossref] [PubMed]
8. Znaor A, Lortet-Tieulent J, Jemal A, et al. International variations and trends in testicular cancer incidence and mortality. Eur Urol 2014;65:1095-106. [Crossref] [PubMed]
9. Huang J, Chan SC, Tin MS, et al. Worldwide Distribution, Risk Factors, and Temporal Trends of Testicular Cancer Incidence and Mortality: A Global Analysis. Eur Urol Oncol 2022;5:566-76. [Crossref] [PubMed]
10. WHO Classification of Tumours Editorial Boards. Urinary and male genital tumours. Lyon (France): International Agency for Research on Cancer; 2022.
11. Amin MB, Edge SB, Greene FL, et al. AJCC Cancer Staging Manual. 8th edition. New York: Springer; 2017.
12. Aggarwal N, Parwani AV. Spermatocytic seminoma. Arch Pathol Lab Med 2009;133:1985-8. [Crossref] [PubMed]
13. Twa DDW, Mottok A, Savage KJ, et al. The pathobiology of primary testicular diffuse large B-cell lymphoma: Implications for novel therapies. Blood Rev 2018;32:249-55. [Crossref] [PubMed]
14. Kim I, Young RH, Scully RE. Leydig cell tumors of the testis. A clinicopathological analysis of 40 cases and review of the literature. Am J Surg Pathol 1985;9:177-92. [Crossref] [PubMed]
15. Young RH, Koelliker DD, Scully RE. Sertoli cell tumors of the testis, not otherwise specified: a clinicopathologic analysis of 60 cases. Am J Surg Pathol 1998;22:709-21. [Crossref] [PubMed]
16. Idrees MT, Ulbright TM, Oliva E, et al. The World Health Organization 2016 classification of testicular non-germ cell tumours: a review and update from the International Society of Urological Pathology Testis Consultation Panel. Histopathology 2017;70:513-21. [Crossref] [PubMed]
17. Berney DM, Warren AY, Verma M, et al. Malignant germ cell tumours in the elderly: a histopathological review of 50 cases in men aged 60 years or over. Mod Pathol 2008;21:54-9. [Crossref] [PubMed]
18. Wheater MJ, Manners J, Nolan L, et al. The clinical features and management of testicular germ cell tumours in patients aged 60 years and older. BJU Int 2011;108:1794-9. [Crossref] [PubMed]
19. Verhoeven RHA, Gondos A, Janssen-Heijnen MLG, et al. Testicular cancer in Europe and the USA: survival still rising among older patients. Ann Oncol 2013;24:508-13. [Crossref] [PubMed]
20. Wu X, Zhou M, Lyu J, et al. Competing risk nomogram predicting cause-specific mortality in older patients with testicular germ cell tumors. Front Med (Lausanne) 2024;11:1327485. [Crossref] [PubMed]
21. Spermon JR, Witjes JA, Kiemeney LA. Difference in stage and morphology-adjusted survival between young and elderly patients with a testicular germ cell tumor. Urology 2002;60:889-93. [Crossref] [PubMed]
22. Inci K, Dogan HS, Akdogan B, et al. Does age affect the prognosis of patients with testicular germ cell tumor? Urol Int 2007;79:117-23. [Crossref] [PubMed]
23. Gillessen S, Sauvé N, Collette L, et al. Predicting Outcomes in Men With Metastatic Nonseminomatous Germ Cell Tumors (NSGCT): Results From the IGCCCG Update Consortium. J Clin Oncol 2021;39:1563-74. [Crossref] [PubMed]
24. Albers P, Albrecht W, Algaba F, et al. EAU guidelines on testicular cancer: 2011 update. Eur Urol 2011;60:304-19. [Crossref] [PubMed]
25. Subik MK, Gordetsky J, Yao JL, et al. Frozen section assessment in testicular and paratesticular lesions suspicious for malignancy: its role in preventing unnecessary orchiectomy. Hum Pathol 2012;43:1514-9. [Crossref] [PubMed]