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NCCN Flash Updates: NCCN Guidelines Updated for Testicular Cancer

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®), the NCCN Drugs & Biologics Compendium (NCCN Compendium^®), the NCCN Radiation Therapy Compendium™, and the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC™), for Testicular Cancer. These NCCN Guidelines^® are currently available as Version 1.2024.

Link directly to the Updates section of the NCCN Guidelines: Testicular Cancer

Global Changes

References updated throughout the guidelines.
CT and MRI contrast recommendations updated throughout the guidelines.
Use of "salvage" replaced throughout the guidelines.

TEST-1

Primary treatment, Radical inguinal orchiectomy
- Footnote d applied: Although rare, when a patient presents with rapidly increasing beta-hCG or AFP and symptoms related to disseminated disease with a testicular mass, chemotherapy can be initiated immediately without waiting for a biopsy diagnosis or performing orchiectomy. However, orchiectomy should be performed at completion of chemotherapy.

SEM-1

Footnote i modified: For select cases of clinical stage IIA disease with borderline retroperitoneal lymph nodes, waiting ~~4–6~~4 weeks and repeating imaging (CT or MRI ~~chest/abdomen/pelvis with contrast~~) to confirm staging before initiating treatment can be considered. (Also for SEM-3, and footnote n on NSEM-3)

SEM-2

Stage IS, follow-up option modified: Repeat elevated serum tumor marker measurement and assess with imaging: Chest/abdomen/pelvis CT (with contrast) to scan for evaluable disease.
Footnote k revised: Recommend ~~abdomen/pelvis CT scan and chest x-ray or CT scan~~ imaging within the 4 weeks prior to the initiation of chemotherapy to confirm staging, even if the scan was done previously. (Also for footnote m on NSEM-2)

SEM-3

Stage IIA, primary treatment option added: Nerve-sparing RPLND
- Follow-up added: See Follow-up for Seminoma, Table 3
Footnote s added: Providers should engage in shared decision-making for Stage IIA seminoma that includes informing patients of the recurrence rates and potential for dual-therapy with each treatment option.
Footnote x added: RPLND is recommended within 4 weeks of CT scan and within 7–10 days of confirmation of normal tumor markers.
Footnote y added: See Principles of Surgery for Germ Cell Tumors.
Footnote z added: Recommend referral to a high-volume center.
Footnote aa added: For nonbulky IIB, ≤3 cm in transaxial long axis.

SEM-4

Positive for viable seminoma, follow-up option modified: Incomplete resection or positive biopsy
Footnote dd added: Consider referral to a high-volume center. Assessment of resectability should be performed.

SEM-5

Footnote hh modified: To assess response after treatment, CT with contrast or MRI with and without contrast of chest/abdomen/pelvis and any other sites of disease is recommended. FDG-PET from skull base to mid thigh may also be considered in assessing treatment response and residual masses following chemotherapy in patients with seminoma. (Also for SEM-6, SEM-7)

SEM-7

Prior first- and second-line conventional dose chemotherapy
- Third-line therapy option added: Microsatellite instability/mismatch repair (MSI/MMR) or tumor mutational burden (TMB) testing if progression after high-dose chemotherapy or third-line therapy
Prior high-dose chemotherapy
- Third-line therapy option added: MSI/MMR or TMB testing if progression after high-dose chemotherapy or third-line therapy
Footnote removed: Microsatellite instability/mismatch repair (MSI/MMR) or tumor mutational burden (TMB) testing if progression after high-dose chemotherapy or third-line therapy.

NSEM-1

Footnote c modified: CT with contrast and MRI with and without contrast. (Also for NSEM-4)
Footnote removed: With and without contrast.

NSEM-4

Post first-line chemotherapy management
- Residual embryonal, yolk sac, choriocarcinoma, or seminoma element
  - Option modified: Chemotherapy (preferred)for 2 cycles (EP or TIP or VIP or VeIP)
  - Option added: Surveillance for select patients
Footnote u added: Surveillance is a reasonable alternative to chemotherapy for patients with residual masses that have been completely resected if all of the residual masses have less than 10% viable cancer cells in the resected tissue.

NSEM-5

pN2, option modified: Chemotherapy ~~(preferred)~~: EP for 2 cycles
pN3; option modified: Chemotherapy preferred: BEP for 3 cycles or EP for 4 cycles
pN3, option added: Surveillance

NSEM-6

Footnote x modified: To assess response after treatment, MRI with and without contrast or CT with contrast of chest/abdomen/pelvis and any other sites of disease is recommended. FDG-PET has no role in assessing treatment response and residual masses following chemotherapy in patients with nonseminoma. (Also for NSEM-8, NSEM-9, and NSEM-10)

TEST-A (1 of 2 3)

Footnote f added: With and without contrast (Also for TEST-A 2, TEST-A 3, and footnote e on TEST-B 1, TEST-B 2, and TEST-B 3)

TEST-A (2 of 3)

Surveillance Table 4 added for Clinical Stage IIA Seminoma: Post-Primary RPLND and NOT Treated with Adjuvant Chemotherapy
- Recurrence column added: If Recurrence, treat according to extent of disease at relapse

TEST-A (3 of 3)

Surveillance Table 5 added for Clinical Stage IIA Seminoma: Post-Primary RPLND and Treated with Adjuvant Chemotherapy
- Recurrence column added: If Recurrence, treat according to extent of disease at relapse
Footnote k modified: Patients with FDG-PET-negative residual mass measuring >3 cm following chemotherapy should undergo an MRI with and without contrast or abdomen/pelvis CT scan with contrast every 6 months for the first year, then annually for 5 years.

TEST-B (1 of 3)

Table 6
- Chest x-ray, months 3 and 4 surveillance recommendations modified: ~~Annually~~ As clinically indicated

TEST-F

High-Dose Chemotherapy Regimens
- Preferred regimen clarified:
  - Carboplatin 700 mg/m2/day (body surface area) IV administered on days -5, -4, -3
  - Etoposide 750 mg/m2/day IV administered on days -5, -4, -3
  - Administer days -5, -4, and -3 ~~days~~ before peripheral blood stem cell infusion for 2 cycles

TEST-G (1 of 3)

Preferred Regimens (High-Dose Chemotherapy)
Carboplatin/etoposide regimen clarified:
- Carboplatin 700 mg/m2/day(body surface area) IV administered on days -5, -4, -3
- Etoposide 750 mg/m2/day IV administered on days -5, -4, -3
- Administered days -5, -4, and -3 ~~days~~ before peripheral blood stem cell infusion for 2 cycles

TEST-H (1 of 2)

Principles of Surgery for Germ Cell Tumors
- Bullet 1, sub-bullet 1 added: When a patient presents with a testicular mass, rapidly increasing beta-hCG or AFP, metastatic disease on imaging, and symptoms related to disseminated disease, chemotherapy can be initiated immediately without waiting for orchiectomy or a biopsy-proven histologic diagnosis. However, radical inguinal orchiectomy should be performed at completion of chemotherapy.
- Bullet 2 modified: ~~A template dissection or a nerve-sparing~~ Nerve-sparing and/or template dissection approach to minimize the risk of ejaculatory disorders should be considered in patients undergoing primary RPLND for stage I nonseminoma.
Testis-Sparing Surgery (TSS)
- Indications for TSS
  - Bullet 1 modified: Synchronous bilateral germ cell tumors, a solitary testicle with a mass suspicious for germ cell tumor, or a functionally solitary testicle with adequate gonadal function with respect to androgen production or sperm production(eg, history of contralateral testicular atrophy).
  - Bullet removed: Non-palpable testicular masses <2 cm are associated with benign tumors in up to 80% of patients, and therefore, TSS may be considered in these patients in whom TSS is technically feasible.

TEST-H (2 of 2)

Principles of Surgery for Germ Cell Tumors
- Section added: Retroperitoneal Lymph Node Dissection (RPLND)
  - Bullet added: A template dissection or a nerve-sparing approach to minimize the risk of ejaculatory disorders should be considered in patients undergoing primary RPLND for stage I nonseminoma.
  - Bullet added: The “split and roll” technique in which lumbar vessels are identified and sequentially ligated allows resection of all lymphatic tissue around and behind the great vessels (ie, aorta, IVC) and minimizes the risk of an in-field recurrence.
  - Bullet added: Referral to high-volume centers should be considered for RPLND.
  - Bullet added: Minimally invasive laparoscopic or robotic approaches to RPLND have limited long-term data and relatively high adjuvant chemotherapy use. Therefore, minimally invasive RPLND is not recommended as standard management, but can be considered in highly selected cases at high-volume centers.
- Postchemotherapy Setting
  - Bullet added: Completeness of resection is a consistent independent predictor of clinical outcome. In postchemotherapy RPLND, surgical margins should not be compromised in an attempt to preserve ejaculation. Additional procedures and resection of adjacent structures may be required.
  - Bullet removed: Referral to high-volume centers should be considered for surgical resection of masses postchemotherapy.
  - Bullet removed: Limited data suggest increased frequency of aberrant recurrences with the use of minimally invasive laparoscopic or robotic approaches to RPLND. Therefore, minimally invasive RPLND is not recommended as standard management, but can be considered in highly selected cases at high-volume centers.

TEST-I

Principles of Imaging
- Staging
  - Pure Seminoma and Nonseminoma, bullet 1 modified: Abdomen/pelvis CT scan with contrast and chest x-ray or CT scan or abdomen/pelvis MRI with and without contrast is recommended within 4 weeks prior to the initiation of chemotherapy, RPLND, or RT to confirm staging, even if scan was performed previously.
- Surveillance
  - Pure Seminoma and Nonseminoma, bullet 1 modified: MRI with and without contrast can be considered ~~in select circumstances~~ in place of an abdomen/pelvis CT.

For the complete updated versions of the NCCN Guidelines, NCCN Guidelines with NCCN Evidence Blocks™, the NCCN Drugs & Biologics Compendium (NCCN Compendium^®), the NCCN Biomarkers Compendium^®, the NCCN Chemotherapy Order Templates (NCCN Templates^®), the NCCN Radiation Therapy Compendium™, and the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC™), please visit NCCN.org.

To view the NCCN Guidelines for Patients^®, please visit NCCN.org/patientguidelines.

Free NCCN Guidelines apps for iPhone, iPad, and Android devices are now available! Visit NCCN.org/apps.

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