testicular%20cancer
TESTICULAR CANCER

Testicular cancer is a rare neoplasm that arises from the testis. It commonly presents as a painless testicular mass.

It has high prevalence in young and middle-aged men in the age of 15-40 years old.

It is a highly treatable disease with a high cure rate.

Testicular primary germ cell tumors coming from the malignant transformation of primordial germ cells make up 95% of all testicular cancer.

 

Surveillance

Seminoma

Stage I

  • Orchiectomy is usually curative for stage I seminoma
  • Postoperatively, surveillance is the preferred treatment for pT1-pT3 tumors especially for compliant patients since there is no survival advantage of radiation or chemotherapy over surveillance & treatment-related morbidity is avoided
    • Patients under surveillance need to be followed with periodic history review & PE, chest x-ray, & abdominal/pelvic CT scan 
  • Risk factors for relapse or occult metastatic disease include tumor size >4 cm & rete testis invasion
    • Patients who relapse may be alternatively treated w/ chemotherapy or radiation

Nonseminoma

Stage I

  • >70% of patients w/ stage I nonseminoma are cured w/ orchiectomy alone
  • Predictors for relapse or occult metastatic disease include lymphovascular invasion, predominance of embryonal carcinoma component, or a T2-T4 primary tumor
  • For patients w/ low-risk disease (vascular invasion absent), negative CT scan & tumor markers, & who are committed, surveillance is the preferred treatment option
    • Surveillance prevents acute & long-term adverse effects from overtreatment
    • Patients under surveillance need to be followed with periodic history review & PE, chest x-ray, abdominal/pelvic CT scan & serum tumor markers
    • For stage IB nonseminoma, consider surveillance for T2 only
    • Consider adjuvant chemotherapy or nerve-sparing RPLND in noncompliant patients or those unwilling to undergo surveillance

Pharmacotherapy

Chemotherapy
Seminoma

Stage I

  • A relapse-free survival is achieved by approximately 90% of patients w/ retroperitoneal masses <3 cm in diameter
  • Patients who relapse are alternatively treated w/ chemotherapy
    • Single-agent Carboplatin given for 1-2 cycles is as effective as adjuvant radiation therapy in relapse prevention

Stage II

  • Nonbulky retroperitoneal disease, eg stage IIA (lymph node mass <2 cm) & small IIB (lymph node mass 2-5 cm) may be treated w/ a Cisplatin-based chemotherapy which includes the following:
    • Bleomycin, Etoposide, & Cisplatin (BEP) chemotherapy for 3 cycles is the standard treatment
    • 4 cycles of Etoposide & Cisplatin (EP) are given to patients w/ contraindications to Bleomycin
  • Bulkier disease (tumors >5 cm) has a higher relapse rate after radiation, thus a Cisplatin-based chemotherapy as above is the preferred treatment for some stage IIB & all IIC patients

Nonseminoma

Stage I

  • High-risk stage I patients (vascular invasion present) are treated w/ 1-2 cycles of BEP
    • Survival is the same as w/ surveillance
  • Stage IS patients are treated w/ chemotherapy, eg 3 cycles of BEP or 4 cycles of EP
    • Chemotherapy is preferred over primary RPLND because of the high prevalence of disseminated disease

Stage II

  • Treatment is based on the levels of serum tumor markers after orchiectomy
  • Disseminated disease is treated w/ chemotherapy due to the high relapse rate after RPLND
    • For patients w/ good prognosis, 3 cycles of BEP or 4 cycles of EP are acceptable combination chemotherapy regimens
  • Patients w/ stage II nonseminoma & persistently elevated tumor markers are generally treated as stage III & given chemotherapy for good-risk nonseminoma

Risk-Directed Chemotherapy

  • Regardless of histological type, the treatment for advanced or metastatic GCT is based upon the International Germ Cell Cancer Consensus Group (IGCCCG) risk stratification system which categorizes patients’ risk into good, intermediate or poor according to their pretreatment clinical features since treatment may bring about significant toxicities
  • IGCCCG system assesses the histology, primary tumor site, metastatic disease & post-orchiectomy serum levels of tumor markers & provides prognosis for metastatic disease treated w/ chemotherapy
  • Goals are to obtain maximum efficacy w/ minimal toxicity in patients w/ good risk & a more effective therapy w/ tolerable toxicity in patients w/ intermediate & poor risk

    Risk Status

    Seminoma

    Nonseminoma

    Good

    5-yr PFS1 82%
    5-yr survival 86%

    5-yr PFS1 89%
    5-yr survival 92%

    All of the following:
    Any primary site
    No nonpulmonary visceral metastases
    Normal AFP
    Any hCG
    Any LDH

    All of the following:
    Testis/retroperitoneal primary site
    No nonpulmonary visceral metastases
    AFP <1000 ng/mL
    hCG <5000 IU/L (1000 ng/mL)
    LDH <1.5 x ULN2

    Intermediate

    5-yr PFS1 67%
    5-yr survival 72%

    5-yr PFS1 75%
    5-yr survival 80%

    All of the following:
    Any primary site
    Nonpulmonary visceral metastases
    Normal AFP
    Any hCG
    Any LDH

    Testis/retroperitoneal primary site &
    No nonpulmonary visceral metastases &
    AFP 1000 - 10,000 ng/mL or
    hCG 5000 - 50,000 IU/L or
    LDH 1.5 - 10 x ULN2

    Poor

    No patients are classified as poor
    prognosis

    5-yr PFS1 41%
    5-yr survival 48%

    Mediastinal primary site or
    Nonpulmonary visceral metastases or
    AFP >10,000 ng/mL or
    hCG >50,000 IU/L (10,000 ng/mL) or
    LDH >10 x ULN2

  • 1PFS: Progression-free survival
    2ULN: Upper limit of normal

  • A durable complete response (complete absence of clinical evidence of tumor on PE & imaging along w/ normalization of serum AFP & hCG levels for ≥1 mth) is achieved w/ the following:
    • 3 cycles of BEP or 4 cycles of EP in good-risk patients [stages IIC & III seminoma; stages IS, IIA & IIB (w/ persistent tumor marker elevation), IIC, & IIIA nonseminoma]
    • 4 cycles of BEP is the standard treatment in intermediate- (stage III seminoma w/ non-pulmonary visceral metastases & stage IIIB nonseminoma) & poor-risk patients (stage IIIC nonseminoma)
    • 4 cycles of Etoposide, Cisplatin, & Ifosfamide (VIP) may be given in select patients w/ poor risk stage IIIC nonseminoma or to patients at risk of lung injury from or who may not tolerate Bleomycin

Postchemotherapy Management

  • A CT scan (eg abdominal, pelvic or chest) should be obtained after primary chemotherapy treatment especially in patients w/ evidence of retroperitoneal adenopathy initially as residual metastases resection is an important part of treatment; serum tumor markers are evaluated as well

Seminoma

  • If there is no residual disease or residual mass is present at ≤3 cm & tumor markers are normal, post-treatment surveillance is suggested
  • If residual mass is >3 cm & tumor markers are normal, a PET scan is obtained ≥6 wk after chemotherapy to assess presence of residual viable tumor
    • If PET scan is negative, do post-treatment surveillance
    • If PET scan is positive, resect residual disease (RPLND if technically feasible); 2 additional cycles of chemotherapy are administered if viable tumor is found but is completely excised
      • If resection is technically difficult, surveillance is suggested; 2nd-line chemotherapy is started if there is positive disease progression on imaging, eg 4 cycles of Vinblastine, Ifosfamide, & Cisplatin (VeIP) or Paclitaxel, Ifosfamide, & Cisplatin (TIP)
  • If progressive disease is evident w/ a growing mass or rising tumor markers, patient may be given salvage therapy

Nonseminoma

  • Do tumor marker level determination & imaging studies 4-8 wk after the last cycle of therapy
    • If CT scan revealed no mass or residual mass <1 cm w/ normal tumor markers, ie complete response, may proceed with post-treatment surveillance or in select cases, nerve-sparing bilateral RPLND
    • If tumor markers have normalized but imaging revealed ≥1 retroperitoneal lymph nodes ≥1 cm in diameter, perform nerve-sparing bilateral RPLND
  • Standard of care is resection of all residual masses apparent on scans in patients w/ normal tumor markers or those w/ partial response after chemotherapy
    • If a mature teratoma or necrotic debris is present, may do surveillance
    • If a viable tumor (choriocarcinoma, embryonal carcinoma, seminoma or yolk sac tumor) is present, 2 additional cycles of chemotherapy are administered, eg EP, TIP, VeIP, or VIP 
  • If patient has incomplete response to primary treatment, consider salvage therapy
  • If tumor markers are persistently elevated or are slowly decreasing, surveillance or post-chemotherapy RPLND may be done
    • Post-chemotherapy RPLND is warranted in metastatic nonseminoma w/ a residual retroperitoneal mass & normal post-chemotherapy serum tumor markers

Salvage Treatment

  • Considered 2nd-line therapy, it may be given to patients who failed to improve w/ 1st-line therapy or those who have developed recurrence
  • Treatment is based on response to previous therapy, timing & location of relapse & tumor histology
    • Treat based on extent of disease at relapse
  • 2nd-line chemotherapy regimens for metastatic germ cell tumors include the following:
    • Conventional-dose regimens: Vinblastine, Ifosfamide, Cisplatin (VeIP); Paclitaxel, Ifosfamide, Cisplatin (TIP)
    • High-dose regimens: Carboplatin plus Etoposide w/ peripheral blood stem cell infusion for 2 cycles or Paclitaxel & Ifosfamide followed by high-dose Carboplatin plus Etoposide w/ peripheral blood stem cell support for 3 cycles
  • Patients who have not received prior chemotherapy (chemotherapy naïve patients) are treated based on their risk status
  • Favorable prognostic factors to conventional dose 2nd-line chemotherapy are testicular primary tumor, prior complete remission after having received 1st-line chemotherapy & low levels of post-orchiectomy tumor markers & volume of disease
    • Ifosfamide, Cisplatin & either Etoposide or Vinblastine can induce a long-term complete response in approximately 25% of patients
    • TIP was associated w/ durable remission in almost two-thirds of patients
    • Alternatives to above-mentioned conventional-dose chemotherapies include a clinical trial (preferred) or high-dose chemotherapy
  • If response is incomplete or patient relapses following chemotherapy w/ 2nd-line conventional dose, give high-dose chemotherapy (if not previously given) or a clinical trial participation
    • High-dose therapy is the standard of care for these patients & has been suggested to be the treatment of choice for relapsed or refractory disease
    •  Surgical salvage must be considered in highly selected patients w/ chemorefractory disease limited to a single resectable site
      • Resection of any residual mass after salvage chemotherapy remains a potential curative option

  • Patients w/ unfavorable prognostic features, ie extratesticular primary tumor, incomplete response to 1st-line chemotherapy, or high levels of tumor markers & volume of disease, may be given a clinical trial participation (preferred), 2nd-line conventional-dose therapy (VeIP or TIP) or high-dose chemotherapy; alternative options include palliative chemotherapy or salvage surgery if solitary site
    • High-dose therapy can be considered in patients w/ a testicular primary tumor & rising post-orchiectomy tumor markers during 1st-line chemotherapy
  • Late-relapsing tumors, ie occurring after >2 yr of achieving complete remission or completing primary therapy, are treated w/ aggressive surgery if resectable (preferred) & chemotherapy w/ conventional- or high-dose regimens
    • Consider stereotactic or conventional radiotherapy if refractory disease is unresectable but localized
  • Palliative therapy w/ chemotherapy or radiation must be considered in patients w/ either persistent or recurrent disease
    • Regimens for metastatic germ cell tumors or patients w/ Cisplatin-resistant or refractory GCT (relapse occurring w/in 4-8 wk following initial chemotherapy or patients w/ progressive disease despite platinum-based therapy or those relapsing shortly after high-dose chemotherapy) include Gemcitabine & Oxaliplatin; Gemcitabine & Paclitaxel; Gemcitabine, Paclitaxel & Oxaliplatin; & oral Etoposide
  • Brain metastases are treated w/ a Cisplatin-based chemotherapy alone or in combination w/ radiation therapy &/or surgical resection if clinically indicated & feasible
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