Residency · Residency · Urology

Testicular Cancer: Diagnosis, Staging, and Orchiectomy

Overview

The diagnosis and management of testicular cancer involve several key components, including the interpretation of scrotal ultrasound, measurement of tumor markers such as alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (beta-hCG), and lactate dehydrogenase (LDH), as well as performing a radical inguinal orchiectomy. Staging is guided by the American Joint Committee on Cancer (AJCC) system. Additional considerations include the option of testicular prosthesis placement and counseling regarding fertility preservation.

Epidemiology

Testicular cancer is the most common solid malignancy in men aged 15 to 35 years, with an incidence of approximately 5 to 6 cases per 100,000 men. Its incidence has been increasing over recent decades, and the lifetime risk for an individual is about 0.4%. Several risk factors contribute to the development of testicular cancer. Cryptorchidism significantly increases risk by 3 to 8 times, even if orchiopexy has been performed. A personal history of testicular cancer raises the risk of contralateral disease by 2 to 3 times, while having a first-degree relative with testicular cancer increases risk by 6 to 10 times. Other associated conditions include testicular dysgenesis syndrome, Klinefelter syndrome, infertility, and HIV infection. Despite these risks, the overall cure rate is excellent, exceeding 95% across all stages. Bilateral tumors occur in 2 to 3% of cases, with metachronous tumors (occurring at different times) being more common than synchronous tumors.

Classification

Germ Cell Tumors (95%)

Germ cell tumors (GCTs) constitute about 95% of testicular cancers and are divided into seminomas and non-seminomas.

Seminoma (50-55%)

Seminomas typically present in men aged 30 to 40 years. The most common subtype is classical seminoma, while spermatocytic seminoma occurs in older men and carries an excellent prognosis. Seminomas are both radiosensitive and chemosensitive. Importantly, they never produce AFP; if AFP is elevated, the tumor should be treated as a non-seminoma regardless of histologic findings. Beta-hCG may be mildly elevated in 10 to 20% of seminoma cases.

Non-Seminoma (40-45%)

Non-seminomatous germ cell tumors (NSGCTs) peak in incidence between ages 20 and 30 years and include embryonal carcinoma, yolk sac tumor (the most common in children), choriocarcinoma, and teratoma. These tumors often exhibit mixed histology. NSGCTs tend to behave more aggressively and metastasize earlier than seminomas. Marker production varies by subtype: embryonal carcinoma may produce beta-hCG, yolk sac tumors produce AFP, choriocarcinomas cause markedly elevated beta-hCG levels, and teratomas are marker-negative, chemoresistant, and may persist or grow after chemotherapy.

Non-Germ Cell Tumors (5%)

Non-germ cell tumors account for about 5% of testicular cancers and include Leydig cell tumors, which produce testosterone and are usually benign but may cause gynecomastia or precocious puberty. Sertoli cell tumors are rare and typically benign. Gonadoblastomas are associated with disorders of sex development, such as 46,XY gonadal dysgenesis. Testicular lymphoma is the most common testicular malignancy in men over 60 years of age.

Presentation

Patients with testicular cancer most commonly present with a painless testicular mass or swelling. Some may experience a dull ache or heaviness in the scrotum. Acute testicular pain occurs in 10 to 20% of cases and usually results from hemorrhage or infarction within the tumor. Gynecomastia may develop in tumors that produce beta-hCG. Back pain can indicate retroperitoneal lymphadenopathy, while dyspnea or cough may signal pulmonary metastases. Occasionally, testicular cancer is discovered incidentally on scrotal ultrasound performed for other reasons.

Diagnostic Workup

Scrotal Ultrasound

Scrotal ultrasound is the first-line imaging modality for any scrotal mass. An intratesticular hypoechoic or heterogeneous mass is considered malignant until proven otherwise, with ultrasound sensitivity exceeding 95% for detecting intratesticular tumors. Seminomas typically appear as homogeneous, hypoechoic lesions, whereas non-seminomas tend to be heterogeneous with mixed echogenicity, including cystic and solid components and possible calcifications. Testicular microlithiasis is associated with an increased risk of cancer but does not require biopsy if found in isolation. The contralateral testis should always be examined during ultrasound evaluation.

Serum Tumor Markers (Pre-Orchiectomy)

Serum tumor markers should be drawn before orchiectomy. AFP is elevated in yolk sac tumors and embryonal carcinoma and has a half-life of 5 to 7 days. AFP is never elevated in pure seminoma; if elevated, the tumor must be managed as a non-seminoma due to the likely presence of an unsampled non-seminomatous component. Beta-hCG is elevated in choriocarcinoma (often markedly), embryonal carcinoma, and sometimes seminoma (mild elevation). Its half-life is 24 to 36 hours. Elevated beta-hCG can cause gynecomastia and hyperthyroidism because it mimics thyroid-stimulating hormone (TSH). LDH is a nonspecific marker that correlates with tumor burden and tissue destruction; it is elevated in 40 to 60% of advanced germ cell tumors and is used in the International Germ Cell Cancer Collaborative Group (IGCCCG) risk classification. Tumor markers should be repeated after orchiectomy to assess for normalization.

Staging Imaging

Staging includes computed tomography (CT) scans of the chest, abdomen, and pelvis to evaluate retroperitoneal and thoracic lymph nodes. Brain magnetic resonance imaging (MRI) is indicated if choriocarcinoma is diagnosed or if neurologic symptoms are present. Bone scans are rarely necessary and reserved for symptomatic patients. Positron emission tomography (PET) scans are not used for initial staging but may be employed to evaluate residual masses after chemotherapy in seminoma.

Radical Inguinal Orchiectomy

Technique

Radical inguinal orchiectomy is performed through an inguinal incision, similar to that used for inguinal hernia repair, and not through the scrotum. The spermatic cord is identified at the external inguinal ring, and early clamping of the cord is performed at the internal inguinal ring before manipulating the tumor to minimize hematogenous and lymphatic spread. The testis is then delivered through the inguinal wound. The spermatic cord is divided at the internal ring with suture ligation (high ligation), and the specimen is sent intact for pathological examination. A scrotal approach is contraindicated because it alters lymphatic drainage, increases the risk of local tumor seeding, and compromises accurate staging.

Testicular Prosthesis

Patients should be offered a testicular prosthesis either at the time of orchiectomy or as a delayed procedure. Silicone prostheses are available in various sizes, and placement improves body image and psychological well-being. This option should be discussed during preoperative counseling.

Organ-Sparing Surgery (Rare Indications)

Organ-sparing surgery may be considered in rare cases, such as patients with a solitary testis who have a small tumor less than 2 cm and normal preoperative tumor markers, bilateral tumors, or benign lesions identified on frozen section (e.g., epidermoid cyst or Leydig cell tumor). Intraoperative frozen section analysis guides the decision between partial and radical orchiectomy. If malignancy is confirmed on frozen section, radical orchiectomy is performed.

Pathologic Reporting

Pathology reports should detail the tumor type and subtype, including the percentage of each component in mixed germ cell tumors. Tumor size and pathological T (pT) stage are documented, noting involvement of structures such as the rete testis, hilar soft tissue, epididymis, spermatic cord, and scrotal wall. Lymphovascular invasion (LVI) is a critical prognostic factor, especially for stage I disease management. Margins, particularly the spermatic cord margin, must be assessed. The presence of intratubular germ cell neoplasia (ITGCN), also known as germ cell neoplasia in situ (GCNIS), is reported as a precursor lesion in adjacent testicular parenchyma.

AJCC Staging (8th Edition)

T Stage

The T stage ranges from pTis, indicating germ cell neoplasia in situ (GCNIS), to pT4, which denotes invasion of the scrotum. Tumors limited to the testis without lymphovascular invasion are classified as pT1, with subcategories pT1a for tumors smaller than 3 cm and pT1b for tumors 3 cm or larger. Tumors with lymphovascular invasion or involvement of hilar soft tissue or epididymis are staged as pT2. Invasion of the spermatic cord is pT3.

N Stage (Clinical/Radiographic)

Regional lymph node involvement is staged as N0 for no metastasis, N1 for lymph nodes 2 cm or smaller, N2 for lymph nodes 2 to 5 cm or multiple nodes smaller than 5 cm, and N3 for lymph nodes larger than 5 cm.

S Stage (Serum Markers Post-Orchiectomy)

Serum marker levels after orchiectomy are categorized as S0 for normal markers, S1 for LDH less than 1.5 times the upper limit of normal (ULN), beta-hCG less than 5,000 IU/L, and AFP less than 1,000 ng/mL. S2 corresponds to LDH 1.5 to 10 times ULN, beta-hCG 5,000 to 50,000 IU/L, and AFP 1,000 to 10,000 ng/mL. S3 indicates LDH greater than 10 times ULN, beta-hCG over 50,000 IU/L, and AFP over 10,000 ng/mL.

Stage Grouping

Stage I disease is confined to the testis with normal or declining post-orchiectomy markers. Stage II involves retroperitoneal lymph node metastases, and stage III includes distant metastases such as supradiaphragmatic lymph nodes or visceral involvement.

Fertility Counseling

All patients should be offered sperm banking (cryopreservation) before orchiectomy, ideally prior to surgery and at minimum before any chemotherapy. This recommendation applies even to patients with a normal contralateral testis because chemotherapy can cause temporary or permanent azoospermia. Baseline semen analysis is important since many patients with testicular cancer have pre-existing subfertility. Testosterone levels should be monitored after orchiectomy, as hypogonadism occurs in 10 to 15% of cases. The impact of treatment modalities on fertility varies: surveillance does not affect fertility; radiation therapy carries a risk of scatter radiation to the contralateral testis, which shielding reduces but does not eliminate; chemotherapy causes temporary azoospermia in most patients, with recovery in 60 to 80% within 2 to 5 years, and the risk is dose-dependent on cisplatin; retroperitoneal lymph node dissection (RPLND) can cause ejaculatory dysfunction, specifically retrograde ejaculation, if nerve-sparing techniques are not used.

<image>A diagnostic pathway flowchart for testicular cancer starting with a patient presenting with a scrotal mass. Steps include scrotal ultrasound (intratesticular vs. extratesticular), serum tumor markers (AFP, beta-hCG, LDH), radical inguinal orchiectomy (NOT scrotal), post-orchiectomy marker kinetics assessment, and staging CT chest/abdomen/pelvis. The pathway branches to seminoma vs. non-seminoma based on pathology and markers, with subsequent management tracks indicated. Fertility counseling and sperm banking are highlighted as essential pre-treatment steps. Clinical algorithm format.</image>

<image>An anatomical illustration of the radical inguinal orchiectomy technique showing: 1) inguinal incision location, 2) identification of the spermatic cord at the external ring, 3) early clamping of the cord at the internal ring, 4) delivery of the testis through the inguinal wound, and 5) high ligation and division of the cord at the internal ring. Inset showing why the scrotal approach is contraindicated (altered lymphatic drainage, risk of local seeding). Surgical technique illustration style with stepwise labeling.</image>

<image>A comparison table of testicular tumor subtypes showing ultrasound appearance, tumor markers, and key clinical features for: seminoma (homogeneous hypoechoic, hCG may be mildly elevated, AFP always normal), embryonal carcinoma (heterogeneous, hCG +/-), yolk sac tumor (heterogeneous with cystic spaces, AFP elevated), choriocarcinoma (mixed with hemorrhage, hCG markedly elevated), and teratoma (cystic/solid with calcification, markers negative). Each entry includes a representative ultrasound image illustration and associated serum marker profile. Medical education comparison format.</image>

Clinical Pearls

A solid intratesticular mass detected on ultrasound in a young man should be considered testicular cancer until proven otherwise, and orchiectomy should not be delayed for observation. Scrotal biopsy or scrotal orchiectomy must never be performed; the inguinal approach with early cord clamping at the internal ring is mandatory to maintain oncologic integrity. AFP is never elevated in pure seminoma; if AFP is elevated, the tumor must be managed as a non-seminoma regardless of histology, as this suggests an unsampled non-seminomatous component. Sperm banking should be offered to all patients before orchiectomy and is especially critical prior to chemotherapy, constituting a medicolegal standard of care. Post-orchiectomy tumor marker kinetics are essential for accurate staging; if markers do not normalize according to their expected half-lives (AFP: 5 to 7 days, beta-hCG: 24 to 36 hours), residual disease should be assumed. The lymphatic drainage of the testis follows the gonadal vessels to the retroperitoneum, with the right testis draining to interaortocaval nodes and the left testis draining to para-aortic nodes at the level of the left renal hilum. Testicular microlithiasis alone does not warrant biopsy or orchiectomy; patients should be followed with self-examination and clinical follow-up since the absolute cancer risk remains low.

References

• Gilligan T, et al. AUA/ASCO Guideline: Testicular Cancer. J Urol. 2019;202(4):682-698
• Albers P, et al. EAU Guidelines on Testicular Cancer. Eur Urol. 2023
• NCCN Clinical Practice Guidelines in Oncology: Testicular Cancer, Version 1.2024
• Dieckmann KP, et al. Testicular microlithiasis and testicular germ cell tumors. Nat Rev Urol. 2012;9(5):282-290
• AJCC Cancer Staging Manual, 8th Edition

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