Management of Early Stage Testicular Cancer: AUA Guideline (2019)

American Urological Association(AUA) has released its latest 2019 Guideline on the Management of Early Stage Testicular Cancer.

Testis cancer is the most common solid malignancy in young males. Testis cancer is a relatively rare malignancy, with outcomes defined by specific cancer- and patient-related factors.

Following are the major recommendations:

Initial Management

Diagnosis and Initial Consultation

1. A solid mass in the testis identified by physical exam or imaging should be managed as a malignant neoplasm until proven otherwise. (Clinical Principle)

2. In a man with a solid mass in the testis suspicious for malignant neoplasm, serum tumor markers (AFP, hCG, and LDH) should be drawn and measured prior to any treatment, including orchiectomy. (Moderate Recommendation; Evidence Level: Grade C)

3. Prior to definitive management, patients should be counseled about the risks of hypogonadism and infertility (Moderate Recommendation; Evidence Level: Grade C) and should be offered sperm banking, when appropriate. In patients without a normal contralateral testis or with known subfertility, this should be considered prior to orchiectomy. (Clinical Principle)

4. Scrotal ultrasound with Doppler should be obtained in patients with a unilateral or bilateral scrotal mass suspicious for neoplasm. (Strong Recommendation; Evidence Level: Grade B)

5. Testicular microlithiasis in the absence of solid mass and risk factors for developing a GCT does not confer an increased risk of malignant neoplasm and does not require further evaluation. (Moderate Recommendation; Evidence Level: Grade C)

6. Patients with normal serum tumor markers (hCG and AFP) and indeterminate findings on physical exam or testicular ultrasound for testicular neoplasm should undergo repeat imaging in six to eight weeks. (Clinical Principle)

7. MRI should not be used in the initial evaluation and diagnosis of a testicular lesion suspicious for neoplasm. (Moderate Recommendation; Evidence Level: Grade C)

Orchiectomy

8. Patients with a testicular lesion suspicious for malignant neoplasm and a normal contralateral testis should undergo a radical inguinal orchiectomy; testis-sparing surgery is not recommended. Transscrotal orchiectomy is discouraged. (Strong Recommendation; Evidence Level: Grade B)

9. Testicular prosthesis should be discussed prior to orchiectomy. (Expert Opinion)

10. Patients who have undergone scrotal orchiectomy for malignant neoplasm should be counseled regarding the increased risk of local recurrence and may rarely be considered for adjunctive therapy (excision of scrotal scar or radiotherapy) for local control. (Moderate Recommendation; Evidence Level: Grade C)

Testis-Sparing Surgery

11a. TSS through an inguinal incision may be offered as an alternative to radical inguinal orchiectomy in highly selected patients wishing to preserve gonadal function with masses <2cm and (1) equivocal ultrasound/physical exam findings and negative tumor markers (hCG and AFP), (2) congenital, acquired or functionally solitary testis, or (3) bilateral synchronous tumors. (Conditional Recommendation; Evidence Level: Grade C)

11b. Patients considering TSS should be counseled regarding (1) higher risk of local recurrence, (2) need for monitoring with physical examination and ultrasound, (3) role of adjuvant radiotherapy to the testicle to reduce local recurrence, (4) impact of radiotherapy on sperm and testosterone production, and (5) the risk of testicular atrophy and need for testosterone replacement therapy, and/or subfertility/infertility. (Moderate Recommendation; Evidence Level: Grade C)

11c. When TSS is performed, in addition to the suspicious mass, multiple biopsies of the ipsilateral testicle normal parenchyma should be obtained for evaluation by an experienced genitourinary pathologist. (Moderate Recommendation; Evidence Level: Grade C)

GCNIS Counseling and Management

12. Clinicians should inform patients with a history of GCT or GCNIS of risks of a second primary tumor while rare is significantly increased in the contralateral testis. (Moderate Recommendation; Evidence Level: Grade B)

13a. In patients with GCNIS on testis biopsy or malignant neoplasm after TSS, clinicians should inform patients of the risks/benefits of surveillance, radiation, and orchiectomy. (Moderate Recommendation; Evidence Level: Grade C)

13b. Clinicians should recommend surveillance in patients with GCNIS or malignant neoplasm after TSS who prioritize preservation of fertility and testicular androgen production. (Moderate Recommendation; Evidence Level: Grade C)

13c. Clinicians should recommend testicular radiation (18-20 Gy) or orchiectomy in patients with GCNIS or malignant neoplasm after TSS who prioritize reduction of cancer risk taking into consideration that radiation reduces the risk of hypogonadism compared to orchiectomy. (Moderate Recommendation; Evidence Level: Grade C)

Staging

Serum Tumor Markers

14. Nadir serum tumor markers (AFP, hCG, and LDH) should be repeated at appropriate T1/2 time intervals after orchiectomy for staging and risk stratification. (Moderate Recommendation; Evidence Level: Grade B)

15. For patients with elevated AFP or hCG post-orchiectomy, clinicians should monitor serum tumor markers to establish nadir levels before treatment only if marker nadir levels would influence treatment. (Clinical Principle)

16. For patients with metastatic GCT (Stage IIC or III) requiring chemotherapy, clinicians must base chemotherapy regimen and number of cycles on the IGCCCG risk stratification. IGCCCG risk stratification is based on nadir serum tumor marker (hCG, AFP and LDH) levels obtained prior to the initiation of chemotherapy, staging imaging studies, and tumor histology following radical orchiectomy (Strong Recommendation; Evidence Level: Grade A). Any post-pubertal male, regardless of age, should be treated according to adult treatment guidelines. (Moderate Recommendation; Evidence Level: Grade B)

17. For patients in whom serum tumor marker (AFP and hCG) levels are borderline elevated (within 3x upper limit of normal) post-orchiectomy, a rising trend should be confirmed before management decisions are made as false-positive elevations may occur. (Clinical Principle)

Imaging

18. In patients with newly diagnosed GCT, clinicians must obtain a CT scan of the abdomen and pelvis with IV contrast or MRI if CT is contraindicated. (Strong Recommendation; Evidence Level: Grade B)

19a. In patients with newly diagnosed GCT, clinicians must obtain chest imaging. (Clinical Principle)

19b. In the presence of elevated and rising post-orchiectomy markers (hCG and AFP) or evidence of metastases on abdominal/pelvic imaging, chest x-ray or physical exam, a CT chest should be obtained. (Strong Recommendation; Evidence Level: Grade C)

19c. In patients with clinical stage I seminoma, clinicians should preferentially obtain a chest x-ray over a CT scan. (Moderate Recommendation; Evidence Level: Grade B)

19d. In patients with NSGCT, clinicians may preferentially obtain a CT scan of the chest over a chest x-ray and should prioritize CT chest for those patients recommended to receive adjuvant therapy. (Conditional Recommendation; Evidence Level: Grade C)

20. In patients with newly diagnosed GCT, clinicians should not obtain a PET scan for staging. (Strong Recommendation; Evidence Level: Grade B)

21. Patients should be assigned a TNM-s category to guide management decisions. (Strong Recommendation; Evidence Level: Grade B)

Management

Principles of Management

22. Management decisions should be based on imaging obtained within the preceding 4 weeks and serum tumor markers (hCG and AFP) within the preceding 10 days. (Expert Opinion)

23. Management decisions should be made in a multidisciplinary setting involving experienced clinicians in urology, medical oncology, radiation oncology, pathology, and radiology. (Clinical Principle)

24. Expert review of pathologic specimens should be considered in clinical scenarios where treatment decisions will be impacted. (Moderate Recommendation; Evidence Level: Grade C)

25. In patients with normal serum tumor markers (hCG and AFP) and equivocal imaging findings for metastasis, clinicians may consider repeat imaging in six to eight weeks to clarify the extent of disease prior to making a treatment recommendation. (Clinical Principle)

Seminoma Management – Surveillance/RPLND/Chemotherapy/Radiation

26. Clinicians should recommend surveillance after orchiectomy for patients with stage I seminoma. Adjuvant radiotherapy and carboplatin-based chemotherapy are less preferred alternatives. (Strong Recommendation; Evidence Level: Grade B)

27. For patients with stage IIA or IIB seminoma with a lymph node ≤3cm, clinicians should recommend radiation therapy or multi-agent cisplatin-based chemotherapy based on shared decision-making. (Moderate Recommendation; Evidence Level: Grade B). For patients with IIB seminoma with a lymph node >3 cm, chemotherapy is recommended. (Moderate Recommendation; Evidence Level: Grade B)

Non-Seminoma Management – Surveillance/RPLND/Chemotherapy/Radiation

28. Clinicians should recommend risk-appropriate, multi-agent chemotherapy for patients with NSGCT with elevated and rising post-orchiectomy serum AFP or hCG (i.e. stage TanyN1-2S1). (Strong Recommendation; Evidence Level: Grade B)

29. Clinicians should recommend surveillance for patients with stage IA NSGCT. RPLND or one cycle of bleomycin, etoposide, and cisplatin chemotherapy are effective and appropriate alternative treatment options for patients who decline surveillance or are at risk for non-compliance. (Moderate Recommendation; Evidence Level: Grade B)

30. For patients with stage IB NSGCT, clinicians should recommend surveillance, RPLND, or one or two cycles of bleomycin, etoposide, and cisplatin chemotherapy based on shared decision-making. (Strong Recommendation; Evidence Level: Grade B)

31. Patients with stage I NSGCT and any secondary somatic malignancy (also known as teratoma with malignant transformation) in the primary tumor at orchiectomy should undergo RPLND. (Expert Opinion)

32. Clinicians should recommend RPLND or chemotherapy for patients with stage IIA NSGCT with normal post-orchiectomy serum (S0) AFP and hCG. (Moderate Recommendation; Evidence Level: Grade B)

33. In patients with clinical stage IIB NSGCT and normal post-orchiectomy serum AFP and hCG, clinicians should recommend risk-appropriate, multi-agent chemotherapy. (Moderate Recommendation; Evidence Level: Grade B). Clinicians may offer RPLND as an alternative to chemotherapy to select patients with clinical stage IIB NSGCT with normal post-orchiectomy serum AFP and hCG. (Conditional Recommendation; Evidence Level: Grade C)

34. Among patients who are candidates for RPLND, it is recommended clinicians consider referral to an experienced surgeon at a high-volume center. (Moderate Recommendation; Evidence Level: Grade C)

35. Surgeons with experience in the management of GCT and expertise in minimally invasive surgery may offer a minimally-invasive RPLND, acknowledging the lack of long-term data on oncologic outcomes. (Expert Opinion)

36. Primary RPLND should be performed with curative intent in all patients. RPLND should be performed with adherence to the following anatomical principles, regardless of the intent to administer adjuvant chemotherapy. These principles are applied to both open and minimally-invasive approaches. (Moderate Recommendation; Evidence Level: Grade B).

• A full bilateral template dissection should be performed in patients with suspicious lymph nodes based on CT imaging or intraoperative assessment and in those with somatic-type malignancy in the primary tumor.


• A full bilateral template or modified template dissection may be performed in patients with clinically negative lymph nodes.


• A right modified template dissection may omit the para-aortic lymph nodes below the inferior mesenteric artery. Omission of para-aortic lymph nodes above the inferior mesenteric artery is controversial.


• A left modified template dissection may omit paracaval, precaval, and retrocaval lymph nodes. Omission of interaortocaval lymph nodes is controversial.


• Nerve-sparing should be offered in select patients desiring preservation of ejaculatory function.


• Nerve-sparing attempts should not compromise the quality of the lymph node dissection.


• A complete retroaortic and/or retrocaval lymph node dissection with division of lumbar vessels should be performed when within the planned template.


• The ipsilateral gonadal vessels should be removed in all patients.


• The cephalad extent of the dissection is the crus of the diaphragm to the level of the renal arteries. The caudad extent of disease is the crossing of the ureter over the ipsilateral common iliac artery.

37. After primary RPLND, clinicians should recommend surveillance or adjuvant chemotherapy in patients with NSGCT who have pathological stage II disease that is not pure teratoma. For patients with pN1 and/or pN1-3 pure teratoma, surveillance is preferred. For patients with pN2-3 at RPLND, multi-agent cisplatin-based chemotherapy is preferred. (Moderate Recommendation; Evidence Level: Grade B)

Surveillance for Stage I Testicular Cancer

38. For patients with clinical stage I seminoma choosing surveillance, clinicians should obtain a history and physical examination and perform cross-sectional imaging of the abdomen with or without the pelvis, every 4-6 months for the first 2 years, and then every 6-12 months in years 3-5. Routine surveillance imaging of the chest and serum tumor marker assessment can be obtained as clinically indicated. (Moderate Recommendation; Evidence Level: Grade B)

39. In patients with stage I NSGCT undergoing surveillance after orchiectomy, clinicians should perform a physical examination and obtain serum tumor markers (AFP, hCG +/- LDH) every 2-3 months in year 1, every 2-4 months in year 2, every 4-6 months in year 3, and every 6-12 months for years 4 and 5. (Moderate Recommendation; Evidence Level: Grade C)

40. In patients with stage I NSGCT undergoing surveillance after orchiectomy, radiologic assessment (chest x-ray and imaging of the abdomen with or without the pelvis) should be obtained every 3-6 months in year 1 starting at 3 months, every 4-12 months in year 2, once in year 3, and once in year 4 or 5. (Moderate Recommendation; Evidence Level: Grade B) Men at higher risk of relapse (e.g., lymphovascular invasion) should be imaged with shorter intervals. (Expert Opinion)

41. Patients who relapse on surveillance should be fully restaged and treated based on their TNM-s status. (Moderate Recommendation; Evidence Level: Grade C)

42. Clinicians should inform patients with stage I GCT on surveillance of the <1% risk of late relapse after 5 years. (Moderate Recommendation; Evidence Level: Grade B) Annual serologic and radiographic assessment may be performed thereafter as indicated based upon clinical concerns. (Clinical Principle)

Additional Survivorship

43. Patients with GCT should be monitored for signs and symptoms of hypogonadism. If present, serum AM testosterone and luteinizing hormone levels should be measured. (Clinical Principle)

44. Patients with a history of GCT whose treatment has included radiation therapy, chemotherapy, or both should be advised of the elevated risk of cardiovascular disease (Conditional Recommendation; Evidence Level: Grade C) and should establish regular care with a primary care physician so that modifiable risk factors for cardiovascular disease (e.g., diet, exercise, smoking, serum lipid levels, blood pressure, serum glucose)can be monitored. (Expert Opinion)

45. Patients with a history of GCT whose treatment has included radiation therapy, chemotherapy, or both should be advised of the elevated risk of secondary malignancy (Conditional Recommendation; Evidence Level: Grade C) and should establish regular care with a primary care physician for appropriate health care maintenance and cancer screening as appropriate. (Expert Opinion).

For more details click on the link: www.auanet.org