AUA 2022: AUA Guidelines: Localized Prostate Cancer

(UroToday.com) The 2022 Annual Meeting of the American Urological Association was host to an AUA Guidelines sessions focused on localized prostate cancer, presented by Dr. James Eastham. The guidelines were divided into multiple sections:

1. Risk Assessment
2. Staging
3. Risk-Based Management
4. Principles of Management

• Principles of Active Surveillance
• Principles of Surgery
• Principles of Radiation

Dr. Eastham started with the risk assessment section as follows:

1. Clinicians should use clinical T stage, serum prostate-specific antigen (PSA), Grade Group (Gleason score), and tumor volume on biopsy to risk stratify patients with newly diagnosed prostate cancer. (Strong Recommendation; Evidence Level: Grade A)
2. Clinicians may selectively use tissue-based genomic biomarkers when added risk stratification may alter clinical decision-making. (Expert Opinion)
3. Clinicians should not routinely use tissue-based genomic biomarkers for risk stratification or clinical decision-making. (Moderate Recommendation; Evidence Level: Grade B)
4. Clinicians should perform an assessment of patient and tumor risk factors to guide the decision to offer germline testing that includes mutations known to be associated with aggressive prostate cancer and/or known to have implications for treatment. (Expert Opinion)

Dr. Eastham next elaborated on the risk group classification for clinically localized prostate cancer. He did point out that the most recent update to this version of the guidelines has gotten rid of the “very-low risk” subgroup as these patients are treated similarly to those with “low-risk” disease. 

He highlighted the following regarding the principles of risk assessment:

• Prostate imaging (ultrasound or MRI) is not used to assign clinical stage
• Imaging (e.g. MRI) findings may provide additional information regarding local tumor extent and may thus be utilized in treatment planning
• Certain histologic features, such as intraductal and cribriform patterns, have been associated with worse prognosis. Counseling an individual patient in these instances is critical. 

Next, Dr. Eastham moved on to the staging section as follows:

5. Clinicians should not routinely perform abdomino-pelvic computed tomography (CT) scan or bone scan in asymptomatic patients with low- or intermediate-risk prostate cancer. (Expert Opinion)
6. Clinicians should obtain a bone scan and either pelvic multi-parametric magnetic resonance imaging (mpMRI) or CT scan for patients with high-risk prostate cancer. (Strong Recommendation; Evidence Level: Grade B)
7. In patients with prostate cancer at high risk for metastatic disease with negative conventional imaging, clinicians may obtain molecular imaging to evaluate for metastases. (Expert Opinion)

• This latest statement represents a modification to the previous version of the guidelines. Significantly, patients in the AUA guidelines being considered for molecular imaging must have prior negative conventional imaging. This contrasts with other guidelines such as those from the NCCN that do not have this requirement prior to considering molecular imaging.
• Clinicals should use a risk-based approach in selecting patients with newly diagnosed prostate cancer for imaging studies
• Data to date supporting a clinical benefit to novel imaging modalities for patients with negative conventional imaging remain quite limited; however, the Panel did conclude that clinicians may offer molecular imaging (PSMA PET) in patients at high risk for metastatic disease based on the demonstrated enhanced staging accuracy

Next, Dr. Eastham moved on to the risk-based management section as follows:

8. Clinicians should inform patients that all prostate cancer treatments carry risk. The risks of treatment, in particular to patients’ urinary, sexual, and bowel function, must be incorporated with the risk posed by the cancer, patient life expectancy, comorbidities, pre-existing medical conditions, and patient preferences to facilitate a shared decision-making approach to management. (Clinical Principle)
9. Clinicians should provide an individualized risk estimate of post-treatment prostate cancer recurrence to patients with prostate cancer. (Clinical Principle)
10. For patients with low-risk prostate cancer, clinicians should recommend active surveillance as the preferred management option. (Strong Recommendation; Evidence Level: Grade A)
11. In asymptomatic patients with prostate cancer and limited life expectancy (determined on a patient-specific basis), clinicians should recommend watchful waiting. (Strong Recommendation; Evidence Level: Grade A)
12. For patients with favorable intermediate-risk prostate cancer, clinicians should discuss active surveillance, radiation therapy, and radical prostatectomy. (Strong Recommendation; Evidence Level: Grade A)
13. Clinicians should inform patients with intermediate-risk prostate cancer considering whole gland or focal ablation that there are a lack of high-quality data comparing ablation outcomes to radiation therapy, surgery, and active surveillance. (Expert Opinion)
14. For patients with unfavorable intermediate- or high-risk prostate cancer and estimated life expectancy greater than 10 years, clinicians should offer a choice between radical prostatectomy or radiation therapy plus androgen deprivation therapy (ADT). (Strong Recommendation; Evidence Level: Grade A)
15. Clinicians should not recommend whole gland or focal ablation for patients with high-risk prostate cancer outside of a clinical trial. (Expert Opinion)
16. Clinicians may recommend palliative ADT alone for patients with high-risk prostate cancer, local symptoms, and limited life expectancy. (Expert Opinion)

Next, Dr. Eastham moved on to the principles of management section as follows:

Principles of Active Surveillance:

17. Patients managed with active surveillance should be monitored with serial PSA values and repeat prostate biopsy. (Expert Opinion)

• Patients managed with active surveillance need to be counseled regarding the importance of continued follow-up as part of this management strategy
  • PSA (no more frequently than every 6 monrhs)
  • Updated symptom assessment
  • Physical examination with DRE (every 1-2 years)
  • Serial PSA increases, new DRE abnormalities, or other concerns for clinical progression should prompt re-evaluation with MRI and possible prostate biopsy; less frequently, direct conversion to treatment may be considered.

18. In patients selecting active surveillance, clinicians should utilize mpMRI to augment risk stratification, but this should not replace periodic surveillance biopsy. (Expert Opinion)

• Multiparametric MRI should be obtained if the initial (diagnostic) prostate biopsy was performed without MRI guidance

1. PIRADS 4 or 5: Timely repeat (confirmatory) targeted biopsy is recommended, with disease risk re-established based on these biopsy results
2. PIRADS 1, 2, or 3: Repeat biopsy may be performed within approximately 12 months after diagnosis

Principles of Surgery

19. In patients electing radical prostatectomy, nerve-sparing, when oncologically appropriate, should be performed. (Moderate Recommendation; Evidence Level: Grade B)
20. Clinicians should inform patients that pelvic lymphadenectomy provides staging information, which may guide future management, but does not have consistently documented improvement in metastasis-free, cancer-specific, or overall survival. (Moderate Recommendation; Evidence Level: Grade B)
21. Clinicians should use nomograms to select patients for lymphadenectomy. The potential benefit of identifying lymph node positive disease should be balanced with the risk of complications. (Clinical Principle)
22. Clinicians performing pelvic lymphadenectomy should perform an extended dissection, which improves staging accuracy compared to a limited dissection. (Moderate Recommendation; Evidence Level: Grade: B)
23. Clinicians should complete a radical prostatectomy if suspicious regional nodes are encountered intraoperatively. (Moderate Recommendation; Evidence Level: Grade C)
24. Clinicians should risk stratify patients with positive lymph nodes identified at radical prostatectomy based on pathologic variables and postoperative PSA. (Expert Opinion)
25. Clinicians may offer patients with positive lymph nodes identified at radical prostatectomy and an undetectable post-operative PSA adjuvant therapy or observation. (Conditional Recommendation; Evidence Level: Grade C)
26. Clinicians should not routinely recommend adjuvant radiation therapy after radical prostatectomy. (Strong Recommendation; Evidence Level: Grade A)

Principles of Radiation:

27. Clinicians should utilize available target localization, normal tissue avoidance, simulation, advanced treatment planning/delivery, and image-guidance procedures to optimize the therapeutic ratio of external beam radiation therapy (EBRT) delivered for prostate cancer. (Clinical Principle, Modification to previous version of guidelines)

• Simulation procedures
• Imaging procedures
• Planning procedures

27. Clinicians should utilize dose escalation when EBRT is the primary treatment for patients with prostate cancer. (Strong Recommendation; Evidence Level: Grade A)
28. Clinicians may counsel patients with prostate cancer that proton therapy is a treatment option, but it has not been shown to be superior to other radiation modalities in terms of toxicity profile and cancer outcomes. (Conditional Recommendation; Evidence Level: Grade C)
29. Clinicians should offer moderate hypofractionated EBRT for patients with low- or intermediate-risk prostate cancer who elect EBRT. (Strong Recommendation; Evidence Level: Grade A)
30. Clinicians may offer ultra hypofractionated EBRT for patients with low- or intermediate risk prostate cancer who elect EBRT. (Conditional Recommendation; Evidence Level: Grade B)
31. In patients with low- or favorable intermediate-risk prostate cancer electing radiation therapy, clinicians should offer dose-escalated hypofractionated EBRT (moderate or ultra), permanent low-dose rate (LDR) seed implant, or temporary high-dose rate (HDR) prostate implant as equivalent forms of treatment. (Strong Recommendation; Evidence Level: Grade B)
32. In patients with low- or intermediate-risk prostate cancer electing radiation therapy, clinicians should not electively radiate pelvic lymph nodes. (Strong Recommendation; Evidence Level: Grade B)
33. In patients with low- or favorable intermediate-risk prostate cancer electing radiation therapy, clinicians should not routinely use ADT. (Moderate Recommendation; Evidence Level: Grade B)
34. In patients with unfavorable intermediate-risk prostate cancer electing radiation therapy, clinicians should offer the addition of short-course (four to six months) ADT with radiation therapy. (Strong Recommendation; Evidence Level: Grade A)
35. Clinicians should offer moderate hypofractionated EBRT for patients with high-risk prostate cancer who are candidates for EBRT. (Moderate Recommendation; Evidence Level: Grade C)
36. In patients with unfavorable intermediate- or high-risk prostate cancer electing radiation therapy, clinicians should offer dose-escalated hypofractionated EBRT or combined EBRT + brachytherapy (LDR, HDR) along with a risk-appropriate course of ADT. (Strong Recommendation; Evidence Level: Grade A/B)
37. In patients with high-risk prostate cancer electing radiation therapy, clinicians may offer radiation to the pelvic lymph nodes. (Conditional Recommendation; Evidence Level: Grade B)
38. When treating the pelvic lymph nodes with radiation, clinicians should utilize intensity-modulated radiation therapy (IMRT) with doses between 45 Gy to 52 Gy. (Strong Recommendation; Evidence Level: Grade B)
39. In patients with high-risk prostate cancer electing radiation therapy, clinicians should recommend the addition of long-course (18 to 36 months) ADT with radiation therapy. (Strong Recommendation; Evidence Level: Grade A)
40. When combined ADT and radiation are used, ADT may be initiated neoadjuvantly, concurrently, or adjuvantly. (Conditional Recommendation; Evidence Level: Grade C)
41. When combining ADT with radiation therapy, clinicians may use combined androgen suppression (luteinizing hormone-releasing hormone [LHRH] agonist with an antiandrogen), an LHRH agonist alone, or an LHRH antagonist alone. (Expert Opinion)

Next, Dr. Eastham moved on to the follow-up after treatment section as follows:

18. Clinicians should monitor patients with prostate cancer post therapy with PSA and symptom assessment. (Clinical Principle)

18. Clinicians should support patients with prostate cancer through continued symptom management and encouraging engagement with professional or community-based resources. (Clinical Principle)

• Resources may be engaged at any point (early diagnosis, treatment, post-treatment)

1. Social work services
2. Cancer support groups
3. Patient advocacy organizations
4. Physical/lifestyle survivorship
   1. Dietary/nutritional services
   2. Physical therapy
   3. Pelvic floor rehabilitation
   4. Psychosexual therapy

Finally, Dr. Eastham touched upon future directions:

• Treatment intensification for high-risk disease
• Appropriate utilization of genomic classifiers
• Increased role/uptake of advanced imaging

Clinically localized prostate cancer remains among the most active areas of investigation in urology. Patient care will continue to be refined and enhanced.

Presented by: James Eastham, MD, Professor, Department of Urology, Memorial Sloan Kettering Cancer Center, New York, NY

Written by: Rashid Sayyid, MD, MSc – Urology Chief Resident, Augusta University/Medical College of Georgia, @rksayyid on Twitter during the 2022 American Urological Association (AUA) Annual Meeting, New Orleans, LA, Fri, May 13 – Mon, May 16, 2022.

1. Eastham JA, Auffenberg GB, Barocas DA et al: Clinically localized prostate cancer: AUA/ASTRO guideline part I: introduction, risk assessment, staging and risk-based management. J Urol 2022; https://doi.org/ 10.1097/JU.0000000000002757.
2. Eastham JA, Auffenberg GB, Barocas DA et al: Clinically localized prostate cancer: AUA/ASTRO guideline part II: principles of active surveillance, principles of surgery and follow-up. J Urol 2022; https://doi.org/10.1097/JU.0000000000002758.
3. Eastham JA, Auffenberg GB, Barocas DA et al: Clinically localized prostate cancer: AUA/ASTRO guideline part III: principles of radiation and future directions. J Urol 2022; https://doi.org/10.1097/JU.0000000000002759.