Approach

Any patient with a testicular mass should be referred to a urologist for a diagnostic evaluation. A biopsy is generally not advised in the evaluation of a testicular mass and diagnosis is established by removing and examining the involved testicle.

Patients with a testicular lesion suspicious for malignant neoplasm and a normal contralateral testis should undergo a radical inguinal orchiectomy; transscrotal orchiectomy is discouraged.[2][48]​ In early-stage disease, an orchiectomy is often curative.

Testis sparing surgery (TSS) through an inguinal incision may be offered as an alternative to radical orchiectomy in highly selected patients if the following criteria are met:​[2]

  • Patients wishing to preserve gonadal function with masses <2 cm

  • Equivocal ultrasound/physical exam findings and negative tumor markers (human chorionic gonadotropin [hCG] and alpha-fetoprotein [AFP])

  • Congenital, acquired, or functionally solitary testis

  • Bilateral synchronous tumors

In TSS, multiple biopsies of the ipsilateral testicle normal parenchyma are obtained in addition to the suspicious mass for evaluation simultaneously.​[2]

Patients considering TSS should be informed of the higher risk of local recurrence and the importance of surveillance with physical exam and ultrasound following TSS. The role of adjuvant radiation to reduce local recurrence, the impact of radiation therapy on testosterone and sperm production, and the risk of testicular atrophy, hypogonadism, and subfertility/infertility should be explained.[2][48]

Nadir serum tumor markers should be repeated after orchiectomy at the appropriate half-life intervals per marker for staging and risk stratification.​[2]

The treatment of localized or early-stage germ cell cancer of the testis depends on the histologic classification of the tumor. Surveillance is a safe treatment option in nonmetastatic germ cell cancers of the testis. Although higher rates of recurrence are seen initially with surveillance compared with interventional adjuvant strategies, the overall survival rates do not differ and patients may be spared the short- and long-term toxicities of chemotherapy and radiation therapy.[64]​ More than 95% of patients with early-stage testicular cancer are cured with appropriate therapy, which may include surgery, chemotherapy, and radiation therapy.[65][66]

Patients with a history of germ cell tumor or germ cell neoplasia in situ should be informed of a modestly increased risk of cancer in the contralateral testis, estimated at approximately 2% (15-year cumulative incidence).​[2][67]

Careful follow-up is recommended because highly effective chemotherapy regimens are available.

Early-stage seminoma

Following orchiectomy, treatment options for patients with early-stage seminoma include surveillance, adjuvant chemotherapy, adjuvant radiation therapy, or retroperitoneal lymph node dissection.[2][48]​​ Information on short-term and long-term adjuvant treatment-related toxicity, such as infertility, major cardiac events, and secondary malignancy, should be provided to patients to inform shared decision-making.[68][69]

Stage I seminoma

Oncologic outcomes after diagnosis of stage I seminoma, which includes stage IA (tumor confined to testis) and stage IB (locally invasive tumor with spread beyond tunica albuginea, but no nodal or metastatic disease), are favorable regardless of initial management strategy.[2] 

Surveillance is the preferred first-line strategy for patients with stage I seminoma in whom follow-up is ensured, minimizing the potential adverse effects of radiation or chemotherapy.[2][68][70]​​​ Approximately 15% to 20% of stage I seminoma patients who are observed after orchiectomy and do not receive adjuvant therapy will relapse, but prognosis following chemotherapy for relapsed disease is excellent.[71]​ Similar survival outcomes are observed in stage I seminoma, regardless of postorchiectomy treatment (including careful surveillance and appropriately treated relapse).[72][73]​​​​

If a surveillance strategy is not acceptable to the patient (due to anxiety of recurrence or other reasons) or the patient is unable to adhere to a surveillance schedule, adjuvant carboplatin chemotherapy may be used for one or two cycles in stage I seminoma.[66][74]

Radiation therapy can be considered in patients with stage I seminoma if the patient declines or is not eligible for active surveillance and where adjuvant carboplatin chemotherapy is contraindicated or declined by the patient.[46][75]​​ If offered, radiation therapy is given to the para-aortic lymph nodes in all patients and the ipsilateral iliac nodes in patients with more advanced disease.[76][77]​​ Radiation therapy is not recommended in patients at increased risk for radiation toxicity, including those with a history of prior radiation, horseshoe/pelvic kidney, or inflammatory bowel disease.[48]

Stage II seminoma

Patients with stage IIA or stage IIB seminoma with retroperitoneal lymph node involvement <3 cm in greatest dimension may be offered radiation therapy; multiagent cisplatin-based chemotherapy (i.e., bleomycin, etoposide, and cisplatin [BEP; also known as PEB] or etoposide and cisplatin [EP]); or retroperitoneal lymph node dissection (RPLND).[2][48][68]​​​​​

For patients with IIB seminoma with a lymph node mass ≥3 cm, chemotherapy is the preferred first-line treatment.[2][48]​ International guidance differs in that lymph node size limits are not always defined.[45][46][78]

​In a meta-analyses, radiation therapy and chemotherapy appear to be equally effective in stage IIA, whereas chemotherapy tends to be more effective in stage IIB seminoma.[69]

If offered, radiation therapy is given to the para-aortic lymph nodes and the ipsilateral iliac nodes in patients with stage II disease.[48] Radiation therapy is not recommended in patients at increased risk for radiation toxicity, including those with a history of prior radiation, horseshoe/pelvic kidney, or inflammatory bowel disease.[48]

RPLND may be considered as an option for stage II seminoma patients who wish to avoid chemotherapy- or radiation therapy-related toxicities. It is recommended for patients with normal postorchiectomy tumor markers, and performed within 2 weeks of tumor marker testing and 4 weeks of CT or MRI scan.[2][48]​​​​ Low rates of recurrence and low long-term morbidity have been demonstrated with RPLND, with the potential to avoid the long-term toxicity and secondary neoplasm risk associated with chemotherapy or radiation therapy.[79][80]​​ RPLND should be performed by an experienced surgeon at a high-volume specialist center, ideally as part of a clinical trial.[45][48]​​​​​​ A template dissection or nerve-sparing approach should be considered to reduce the risk of ejaculatory dysfunction.[48]

Several studies have investigated deescalating chemotherapy regimens plus radiation therapy to minimize treatment burden and toxicity. Single-dose carboplatin plus radiation therapy may be a further option for stage IIA disease; however, further research is needed and this is not generally preferred by recent guidelines.[48][81]​​

Early-stage nonseminoma

Treatment options for patients with early-stage (stage I disease or stage II A/B disease [any tumor size; regional nodes <5 cm; with or without slightly raised tumor markers]) nonseminoma testicular cancer include surveillance, chemotherapy, or retroperitoneal lymph node dissection (RPLND) after orchiectomy, depending on specific patient and cancer features.[2]​​ Information on short-term and long-term adjuvant treatment-related toxicity, such as infertility, major cardiac events, and secondary malignancy, should be provided to patients to inform shared decision-making.

Stage I nonseminoma

Surveillance is the preferred option for patients with stage I nonseminoma that has not yet invaded the local structures (no spermatic cord or scrotal involvement), although there is a risk of relapse of up to 50% in those with high risk features (evidence of lymphovascular invasion, invasion of the spermatic cord or scrotum, or with a substantial component of embryonal carcinoma).[82] The relapse rate for all patients with surveillance is between 20% and 30%.[83] Lymphovascular invasion increases the risk of relapse, making surveillance less advisable, but still an option for those where close follow-up can be ensured.[84]

RPLND is an alternative option for patients with stage I nonseminoma, with or without high-risk features.[48] It can be considered if a surveillance strategy is not acceptable to the patient or the patient is unable to adhere to a surveillance schedule. RPLND is performed in patients with normal postorchiectomy tumor markers, within 2 weeks of tumor marker testing and 4 weeks of CT or MRI scan.[2][48]​​​​​ RPLND should be performed by an experienced surgeon at a high-volume specialist center.[48] A template dissection or nerve-sparing approach should be considered to reduce the risk of ejaculatory dysfunction.[48][85]​ Following RPLND, adjuvant chemotherapy may be considered if any significant nonteratomatous disease is discovered in the resected lymph nodes.[2][46][48]​​​​

A single cycle of adjuvant BEP can be considered as an alternative to RPLND for stage I patients, particularly for those with high-risk tumors (evidence of lymphovascular invasion, invasion of the spermatic cord or scrotum, or with substantial component of embryonal carcinoma) and those who decline surveillance.[2][46][86]​ European guidelines favor adjuvant chemotherapy over RPLND for stage I nonseminoma when surveillance is unsuitable or declined[45][46]

Stage II nonseminoma

In patients with stage II A/B nonseminoma, surveillance is not recommended as a first-line option: this group should instead be managed initially with RPLND or chemotherapy.[2][46]​ 

For stage IIA with normal postorchiectomy marker levels, the prognosis is excellent with either treatment option, therefore shared decision-making should be used, incorporating the patient’s medical history, values, and goals. For stage IIB patients with normal postorchiectomy marker levels, chemotherapy is generally preferred as the initial treatment, although RPLND can be considered in highly selected patients. Chemotherapy for stage II A/B patients typically comprises either 3 cycles of BEP or 4 cycles of EP.[2][45][46][48]​​

RPLND is performed in patients with normal postorchiectomy tumor markers, within 2 weeks of tumor marker testing and 4 weeks of CT or MRI scan.[2][48]​​​​ RPLND should be performed by an experienced surgeon at a high-volume specialist center.[48] A template dissection or nerve-sparing approach should be considered to reduce the risk of ejaculatory dysfunction.[48][85]​ Following primary RPLND, adjuvant chemotherapy may be considered if any significant nonteratomatous disease is discovered in the resected lymph nodes.[2][46][48]

For patients with stage II nonseminoma and persistently elevated postorchiectomy marker levels, chemotherapy with 3 cycles of BEP or 4 cycles of EP is recommended due to the increased risk of relapse from micrometastatic disease.[2][45][48]

Advanced testis cancer

Combination chemotherapy is the mainstay of treatment for advanced disease (stage IIC [any tumor size; regional nodes ≥5 cm; with or without slightly raised tumor markers] or stage III [metastatic or spread to regional nodes with high tumor marker levels]), both seminoma and nonseminoma. Chemotherapy regimens and number of cycles are determined by risk stratification (using the International Germ Cell Cancer Collaborative Group classification criteria) based on postorchiectomy tumor marker levels and extent of disease from imaging and tumor histology.[2][48][60][61]​ Patients are categorized as:

  • Good risk: seminoma stage IIC and IIIA/B; nonseminoma stage II and IIIA

  • Intermediate risk: seminoma stage IIIC; nonseminoma stage IIIB

  • Poor risk: nonseminoma stage IIIC

Combination chemotherapy with BEP is considered a standard first-line treatment for those with advanced disease.[87][88] Due to the potential for serious pulmonary toxicity with bleomycin, particularly in older patients, those with reduced kidney function or lung disease, and those who smoke, alternate regimens (such as EP, or etoposide plus ifosfamide plus cisplatin [VIP]) are used in these patients.

For patients with good-risk disease, 3 cycles of BEP or 4 cycles of EP are recommended.[2][48][89] Combination chemotherapy with EP appears to have similar efficacy to BEP in patients with good risk, although a longer course is required.[60][65]​​[89]​ Choice of regimen should take into account risk of complications and patient preferences.

For patients with intermediate- or poor-risk disease, the standard regimen is 4 cycles of BEP. If bleomycin is contraindicated, patients may be offered VIP as an alternate option, given in 4 cycles.[2][48][88][89]​ For prevention of hemorrhagic cystitis due to ifosfamide, mesna is administered with VIP.[90]​ 

Residual masses are commonly seen on postchemotherapy imaging studies of patients with bulky lymph node disease at baseline. Surgical resection, rather than further chemotherapy, is the appropriate first consideration for patients with nonseminoma and residual mass with normal tumor markers (or mildly elevated and not rising).[48][91]​​ If tumor markers are elevated and rising, additional chemotherapy may be considered.

For patients with seminoma, a postchemotherapy positron emission tomography/CT (PET/CT) scan may be used to assess the activity of residual masses greater than 3 cm.[92] If PET scan is positive, repeat imaging in 6-8 weeks may be considered, or resection or biopsy performed to assess for residual seminoma and need for additional therapy.[48] Surgical resection of a pure seminoma can be technically challenging due to the physical characteristics of this cancer subtype. Careful surveillance can be used to follow PET-negative masses or masses less than 3 cm.

Patients with rising markers or a growing mass should be evaluated for additional chemotherapy or surgery.

Relapse

Patients with relapsed testicular cancer are often cured with second-line salvage chemotherapy.

Conventional salvage chemotherapy options for relapse after primary chemotherapy include ifosfamide-containing combination regimens such as vinblastine, ifosfamide, and cisplatin (VeIP), or paclitaxel, ifosfamide, and cisplatin (TIP).[48][93][94]​​​ Alternatively, high-dose sequential carboplatin plus etoposide (CE), with autologous stem cell transplant support can be used.[48]​​[95][96][97][98][99]​​​​​ Paclitaxel and ifosfamide may be incorporated into the high-dose CE regimen (paclitaxel, ifosfamide, carboplatin, and etoposide [TI-CE]).[98]​ Conventional-dose chemotherapy may also be selectively used to reduce tumor bulk or prevent progression prior to high-dose carboplatin and etoposide.[99]

The choice between conventional-dose versus high-dose chemotherapy for second-line/first salvage treatment of testicular cancer following relapse is a focus of research. The international phase III TIGER trial is examining salvage therapy with TIP or TI-CE for relapsed or refractory germ cell tumors.[100]

Surgical salvage may be considered as an option for nonseminoma patients with a solitary, resectable recurrent mass, and for those with late relapse (>2 years after primary treatment) if the mass is resectable.[48]

For patients with relapsed or refractory germ cell cancer, referral to a high volume center and consideration of clinical trial enrollment are recommended.

Use of this content is subject to our disclaimer