A Retrospective Analysis of Testicular Cancer (2007–2025): A Single Institutional Experience

Abstract

Background

Testicular cancer (TC) is the leading cancer among adolescents and young adults (AYAs) aged 15–39 years and one of the most curable cancers.

Objective

The study aims to assess epidemiology, histological classification, stage at diagnosis, prognosis, stage I risk assessment and relationship between prognosis and age in the Center of Chemotherapy and Radiotherapy at Latakia University Hospital.

Methods

318 patients with testicular cancer who had been attended to the Chemotherapy and Radiotherapy Center at Latakia University Hospital from its opening in 2007 until October 2025 were included in this retrospective analysis.

Results

The median age at diagnosis was 32 years. The most prevalent testicular cancer (TC) was germ cell type. Among germ cell tumors, non-seminomatous types (51.6%) were slightly more frequent than seminomatous (45.9%). The most frequent non-seminomatous subtype was: mixed germ cell tumors (29.9%). The majority of TC patients were in stage I. About two-thirds of the seminoma patients were in stage I, while it represented about half of the non-seminoma patients with a significant difference between the two types. Two (2.86%) patients with vascular invasion, 31 (44.29%) with embryonal carcinoma, both vascular invasion and embryonal carcinoma in 8 (11.43%), and no risk factors were detected in 29 (41.43%) patients in non-seminoma. In seminoma, 40 (41.24%) patients reviewed with tumor size >4cm, 5 (5.15%) with rete testis invasion, 19 (19.59%) with both, and no risk factors were detected in 33 (34.02%) patients. No significant difference in the age of patients was shown after categorizing them according to their prognosis.

Conclusion

The findings align with global proportions and can support those interested in the field in reducing disease burden, but further research is needed, especially in Syria and the Middle East due to limited studies.

Plain Language Summary

Testicular cancer is considered an interesting topic in medicine. Although it is common among young men, it remains highly curable when detected early and managed appropriately. This makes it important to study its various aspects, especially epidemiology, which includes examining age distribution (which age groups are most at risk?), affected groups, patient condition at presentation (their laboratory tests and imaging) and the factors that make the disease more dangerous. This is what we have done by collecting data on patients with testicular cancer who presented to Latakia University Hospital, which is considered one of the most important specialized centers for cancer treatment in Syria, from its opening in 2007 until October 2025. This was done in order to determine whether there is a significant difference compared to global rates – regarding the aforementioned aspects – that would need further research, and which may be explained by the successive circumstances the country has experienced and their impact on this type of cancer. However, we did not find a significant difference that would allow us to conclude that there is a problem requiring further investigation. Nevertheless, we plan to extend this research in the future to include the entire country of Syria.

Introduction

Testicular cancer (TC) is relatively rare, accounts for only 0.4% of all male cancers.1 However, it is the leading cancer among adolescents and young adults (AYAs) aged 15–39 years2,3 and its burden is also expected to increase by 2035.4 Testicular germ-cell tumors (GCTs) comprise 95% of malignant tumors arising in the testes (most common site for germ cell tumors in the body5) and are categorized into 2 main histologic subtypes: seminoma and non-seminoma.6 Known risk factors include: cryptorchidism, family history, maternal and perinatal factors (such as low birth weight). Smoking, ethnicity and infections are considered potential factors and require further studies.7 In addition to its relatively low incidence, it is one of the most curable cancers, with a cumulative 10-year survival rate exceeding 90% and a mortality rate of about 0.1% of all tumors, which makes the accurate diagnosis and classification of testicular cancer the basis for making the optimal treatment decision.1,8 In this research, we aimed at providing records of TC cases that were admitted to Latakia University Hospital during the period 2007 and 2025. Furthermore, we managed to study the epidemiological aspects including: histological types and subtypes, age at diagnosis, tumor stages, risk factors and prognosis, to highlight this tumor type, given the limited publication related to it in Syria in particular and the Middle East in general.

Methods

Inclusion Criteria

This retrospective epidemiological-clinical study relied on reviewing the medical records of all patients diagnosed with testicular cancer and admitted to the Chemotherapy and Radiotherapy center at Latakia University Hospital from its opening in 2007 until October 2025.

Exclusion Criteria

Patients with incomplete medical records were excluded. (Further details are provided in the Limitations of the study section).

Data Collection

318 subjects with TC were diagnosed out of 46585 recorded cancer cases during the studied period, which represents 0.68% of all cancer cases. Data were collected regarding: age, pathology reports for histological type, subtypes, TNM classification and risk factors related to recurrence, radiological assessment as testicular ultrasound, CT chest, abdomen, and pelvis, MRI, PET-CT for staging, and laboratory tests including (FP, HCG, LDH) for IGCCC prognostic classification for metastatic germ cell cancers. No predefined primary or secondary endpoints were established. The analysis focused on describing patient characteristics and relevant outcomes.

Statistical Analysis

Categorical variables are presented as frequencies and percentages, while continuous variables are reported as mean ± standard deviation. Group comparisons for continuous variables were performed using the independent samples t-test (two groups) or one-way ANOVA (three or more groups). Categorical variables were compared using the chi-square test or Fisher’s exact test. Results were considered statistically significant when P˂ 0.05. All analyses were performed using R statistical software (version 4.5.2).

Results

Epidemiology

The total number of cases was 318, with mean age of 33.2 ± 10.5 years. The median age was 32 years (minimum: 15, maximum: 76) Figure 1.

Figure 1.

Number of patients according to age group.

Changes in Annual Incidence Rates for Seminoma vs Non-Seminoma

We notice differences in rates between the years, without observing any specific upward or downward trend, with a peak incidence in 2015 for both seminoma and non-seminoma. Figure 2 illustrates the annual incidence rates and their changes over the study period.

Figure 2.

Changes in annual incidence rates for seminoma vs non-seminoma.

Histological Classification

Germ cell tumor is the most common type, accounting for 97.5%. Among them, non‑seminomatous germ cell tumor represents the majority at 51.6%, followed by seminoma at 45.9%. Within the non-seminomatous group, mixed germ cell tumors are the most common 29.9%. The remaining types and their proportions are shown in Table 1.

Table 1.

Distribution of Histological Subtypes

	Frequency	%
GCNIS-related TGCTs	310	97.5%
Seminomas	146	45.9%
Non-seminomatous germ cell tumors	164	51.6%
Non-seminomatous mixed germ cell tumors	95	29.9%
Embryonal carcinoma	33	10.4%
Yolk sac tumors	8	2.5%
Teratomas	12	3.8%
Teratoma with somatic-type malignancy	15	4.7%
Choriocarcinomas and other trophoblastic tumors	1	0.3%
Non–GCNIS-related TGCTs	4	1.26%
Spermatocytic tumors	4
Sex cord-stromal tumors	3	0.94%
Leydig cell tumor	1
Adult granulosa cell tumor	1
Unclassified	1
Haematolymphoid tumors	1	0.3%
Diffuse large B-cell lymphoma	1
Total	318

Stage at Diagnosis

The majority of TC patients were in stage I (n = 167, 57.59%). About two-thirds of the seminoma patients were in stage I, while it represented about half of the non-seminoma patients with a significant difference between the two types (P < 0.0001, Statistical test: Chi-square, p-value = 9.999e-05) Table 2. However, it should be noted that 20 patients (4 for seminoma and 16 for non-seminoma) had no stage, see Limitations of the study section.

Table 2.

Stages for Seminoma and Non-Seminoma

Stage	Total		Seminoma		Non-Seminoma		P
	n	%	n	%	n	%
I	167	57.59	97	68.3	70	47.3	<0.0001
IIa	28	9.66	14	9.86	14	9.46
IIb	29	10	9	6.34	20	13.5
IIc	29	10	19	13.38	10	6.76
III	37	12.76	3	2.1	34	22.97

Prognosis

No significant difference in prognosis was observed among the histology types (P > 0.05, Statistical test: Fisher’s exact test, p-value = 0.9008476) Table 3.

Table 3.

(IGCCCG) Classification for Metastatic Risk Assessment

Total			Seminoma			Non-seminoma			P
Prognosis	n	%	Prognosis	n	%	Prognosis	n	%
Good	90	73.17	Good	36	80	Good	54	69.23	0.9
Intermediate	24	19.51	Intermediate	9	20	Intermediate	15	19.23
Poor	9	7.32	Poor	NA*		Poor	9	11.54

Note: *Not applicable.

Relationship Between Prognosis and Age

No significant difference in the age of patients was shown after categorizing them according to their prognosis (P > 0.05, Statistical test: one-way ANOVA, p-value = 0.7956545) Table 4.

Table 4.

Relationship Between Prognosis and Age

Prognosis	Age (Mean ± SD)	P
Good	33.88 ± 10.59	0.79
Intermediate	32.19 ± 9.26
Poor	33.2 ± 10.18

Stage I Risk Assessment

For seminoma: 40 patients presented with tumor size >4cm, 5 with rete testis invasion, 19 with both, and 33 patients with none of them. For non-seminoma: 2 patients presented with vascular invasion, 31 with embryonal carcinoma, 8 with both, and 29 patients with none of them Table 5.

Table 5.

Stage 1 Risk Factors

Seminoma			Non-Seminoma
Risk Groups	n	%	Risk Groups	n	%
Tumor size > 4cm	40	41.24	Vascular invasion	2	2.86
Rete testis invasion	5	5.15	Embryonal carcinoma	31	44.29
Both	19	19.59	Both	8	11.43
None	33	34.02	None	29	41.43

Discussion

Epidemiology

The median age of patients was 32 years with a range of (15–76) years. We observed that the incidence rate is most common in the age group 30–34 years Figure 1, which aligns with the latest epidemiological study conducted in the Middle East,9 but slightly differs from the global incidence rate.10

Histological Classification

We relied on the WHO 2016 classification for histological typing,11 which was updated in 2022,12 as shown in Table 1. Three hundred and ten patients (97.5%) had germ cell tumors (GCTS), which is recently referred to as “Germ cell neoplasia in situ (GCNIS)-related tumors” according to the previously mentioned classifications. Among germ cell tumors, non-seminomatous types (51.6%) were slightly more frequent than seminomatous (45.9%). The most frequent non-seminomatous subtype was: mixed germ cell tumors (29.9%). The remaining percentages are presented in the table. As previously mentioned, environmental factors, genetics and ethnicity play a significant role in the incidence of testicular cancer, making it essential to compare our findings with those of neighboring countries, despite the limited publication on this topic (Jordan, Lebanon, Saudi Arabia, Egypt).13–17 Nevertheless, the results were not similar, as we observe variations in the proportion of GCTs among total testicular tumors (though they remain the most common). In contrast to our study, some research shows a predominance of seminoma over non-seminoma, while other studies are consistent with our findings. This indicates the importance of epigenetic factors in regulating the occurrence and the histological pattern that will develop.18

Stage at Diagnosis

A good classification of tumors is essential for making optimal therapeutic decisions. The TNM system is the standard, according to the Union for International Cancer Control (UICC) and American Joint Committee on Cancer (AJCC).19,20 According to our data Table 2, 57.59% of patients were diagnosed at stage I (68.3% for seminoma and 47.3% for non-seminoma), which is similar to the results of A. Mohammed15 and M. Khan et al.21 While the proportions for stages IIa, IIb, IIc and III were 9.66%, 10%, 10% and 12.76% respectively, these results are similar to M. Khan et al21 but lower than E Mesha et al,17 and R Singh et al.22 We note that stage I is the most common presentation, and this is important because the cure rate at this stage reaches up to 100% in seminoma and 98–100% in non-seminoma.3 These findings may suggest our patient’s awareness of the importance of prompt medical consultation and early initiation of treatment following symptom onset; however, further studies are needed to investigate this hypothesis, as delayed diagnosis is associated with elevated postoperative tumor markers, metastasis, clinical stage III, and second-line chemotherapy administration.23

Prognosis

The International Germ Cell Cancer Collaborative Group (IGCCCG) classification is fundamental for prognosis and treatment planning in metastatic testicular GCTs. Accurate application (using pre-chemotherapy markers) is essential to avoid misclassification and ensure optimal outcomes.24 Since no patients are classified as poor prognosis, seminoma patients in our study are classified as good prognosis 36 (80%) patients and 9 (20%) as intermediate. For non-seminoma, the outcomes were as follows: 54 (69.23%) patients classified as good prognosis, 15 (19.23%) as intermediate, and 9 (11.54%) as poor Table 3. Since the introduction of this classification system, improvements in both progression-free survival (PFS) and overall survival (OS) have been observed. This is mainly attributed to better estimation of survival rates (95%, 85% and 64% for good, intermediate and poor prognosis, respectively)25 and guiding appropriate treatment decisions, including the selection of chemotherapy protocols, the number of cycles and in some cases the use of radiotherapy (RT).26,27 As observed in the present study, the majority of patients, including both seminoma and non-seminoma cases, were classified within the good prognosis group. This distribution may have important clinical implications, as patients in this category are generally expected to achieve more favorable outcomes under standard treatment protocols. It should be noted that prognosis is determined by multiple factors beyond disease classification, including the patient’s overall health status and individual characteristics. Consequently, the role of personalized medicine has become increasingly important.

Stage I Risk Assessment

For stage I disease, different risk factors have been identified for seminoma and non-seminoma based on histological features in the primary tumor Table 5. In non-seminoma, vascular invasion of blood or lymphatic vessels (LV+) is the most important predictor of micrometastases and subsequent recurrence. There is controversy regarding the consideration of embryonal carcinoma as a risk factor; however, based on decades of clinical experience, our experts support its importance as a risk factor.28 Based on this, the findings were as follows: 2 (2.86%) patients with vascular invasion, 31 (44.29%) with embryonal carcinoma, both vascular invasion and embryonal carcinoma in 8 (11.43%), and no risk factors were detected in 29 (41.43%) patients. In seminoma, tumor size >4cm and rete testis invasion represent risk factors identifying higher-risk patients.29 Forty (41.24%) patients reviewed with tumor size >4cm, 5 (5.15%) with rete testis invasion, 19 (19.59%) with both, and no risk factors were detected in 33 (34.02%) patients. The importance of this classification stems from its direct association with Post-orchiectomy decision-making in stage I GCTs, whether surveillance or adjuvant ChT. As in the presence of one or more risk factors, adjuvant ChT is preferred, whereas surveillance is sufficient in their absence.30,31 It should be noted that a new stratification model for stage I seminoma has been proposed. Categorical tumor size (≤2, >2–5, and >5 cm), presence of RTI, and lymphovascular invasion were used to form three risk groups: low (56.4%), intermediate (41.3%), and high (2.3%) risks with 5-yr cumulative relapse probabilities of 8%, 20%, and 44%, respectively.32 Although this model has shown promising results, current clinical guidelines still rely on the older classification system, despite its recognition as being based on relatively weak prognostic factors.33

Limitations of the Study

Some patients in our country experienced – during certain periods of the civil war – difficulty accessing the essential radiological and laboratory diagnostic tools needed to establish TNM staging and determine prognostic factors. Therefore, we were unable to obtain this information for 4 seminoma patients and 16 non-seminoma patients, despite the availability of their histopathology reports, which were included in the histological classification section. Another issue is that, in addition to seminoma and non-seminoma, the other histological types constitute small subgroups. This may have limited the statistical power of these analyses and should be considered when interpreting nonsignificant findings.

Conclusion

In summary, we found that our data are close to global proportions. These results may provide information that could be useful to TC epidemiologists, clinicians, policy makers, and other stakeholders interested in reducing the burden of TC morbidity and mortality. Given the descriptive nature of the present study, further prospective studies are needed to evaluate long-term follow-up outcomes and explore the effectiveness of different treatment strategies in this patient population. However, we recommend increasing research in this field at other centers due to the limited number of related publications in Syria in particular and the Middle East in general.

Funding Statement

This research did not receive any grant from agencies in the public, commercial, or not-for-profit sectors.

Data Sharing Statement

The data are represented in the manuscript; additional data is available upon request from the corresponding author.

Ethics Approval

Ethical approval was obtained from the local institutional review board (IRB) in Latakia University (Approval No. 602). The Ethics Committee determined that informed consent was not required because only anonymized retrospective data were analyzed. This study was conducted in accordance with the Declaration of Helsinki.

Disclosure

The authors declare that they have no competing interests.