(UroToday.com) The 2023 American Urological Association (AUA) annual meeting held in Chicago, IL between April 28 and May 1st, 2023, was host to the International Prostate Forum, with Dr. Stephen Boorjian discussing the latest 2022 iteration of the joint AUA/ASTRO guidelines for clinically localized prostate cancer, focusing on how these most recent changes have helped him in his practice.
Dr. Boorjian emphasized the key areas of the guidelines to highlight:
- Risk-based assessment and management
- Shared-decision making
- “How to do” or principles of:
- Active surveillance
- Surgery
- Radiation
Beginning with risk assessment, Dr. Boorjian noted that 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 into either low-, intermediate (favorable or unfavorable), or high-risk groups.
With regards to risk assessment with genomic biomarkers:
- Clinicians may selectively use tissue-based genomic biomarkers when added risk stratification may alter clinical decision-making. (Expert Opinion)
- Clinicians should not routinely use tissue-based genomic biomarkers for risk stratification or clinical decision-making. (Moderate Recommendation; Evidence Level: Grade B)
With regards to genetic testing, 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.
For risk-based staging recommendations:
- 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)
- 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)
- 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)
- Dr. Boorjian emphasized that the systematic review for this guidelines synthesis was completed in 2020, and, as such, this recommendation does not fully reflect the more recent literature available over the previous three years
Shared decision-making remains under-utilized, and 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)
Moving on to active surveillance, for patients with low-risk prostate cancer, clinicians should recommend active surveillance as the preferred management option. (Strong Recommendation; Evidence Level: Grade A). Patients managed with active surveillance should be monitored with serial PSA values and repeat prostate biopsy. An individualized monitoring regimen, based on disease risk and life expectancy, is appropriate in this setting.
In patients selecting active surveillance, clinicians should utilize mpMRI to augment risk stratification, but this should not replace periodic surveillance biopsy. (Expert Opinion). A mpMRI should be obtained if the initial diagnostic biopsy was performed without mpMRI guidance. Patients with PIRADS 4 or 5 lesions should undergo timely repeat, confirmatory targeted biopsy, whereas those with PIRADS 1 to 3 lesions recommended to undergo repeat biopsy within 12-18 months of diagnosis. Following this, serial surveillance biopsies are recommended every 1-4 years depending on patient age, health, risk of progression, and preference.
Based on the current available evidence, can we rely on changes in mpMRI score to predict the risk of reclassification? The answer appears to be not with data from Chestnut et al. in 2020 demonstrating that among 132 patients with stable disease on MRI, 31% had progression to Grade Group 2 or worse disease.
Conversely, for patients with favorable intermediate-risk prostate cancer, clinicians should discuss active surveillance, radiation therapy, and radical prostatectomy. (Strong Recommendation; Evidence Level: Grade A). The management of patients with intermediate-risk disease may be informed in part by recent 15-years outcomes data from the ProtecT trial, which included intermediate risk patients (24.1% of the cohort), and demonstrated similar overall survival outcomes compared to low-risk patients.1
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). The optimal treatment for these patients remains a topic of active study, and prior published series and meta-analyses have reported relatively disparate findings as to compare survival following each of these treatment approaches.
Moving on to the principles of surgical management, of patients electing radical prostatectomy, nerve-sparing, when oncologically appropriate, should be performed. The rationale for neurovascular bundle preservation is as follows:
- Consistently associated with decreased risk of erectile dysfunction
- Associated with improved urinary continence
- Not associated with increased risk of positive surgical margins or biochemical recurrence rates
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. Furthermore, 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 associated complications. (Clinical Principle). Numerous nomograms exist, including the Briganti nomogram which was developed in 588 patients undergoing an extended PLND and found to have a predictive accuracy of 88%.2 The 5% threshold from the model is commonly used to decide on performing a PLND.
Can we use PSMA PET scans to reliably predict the presence/absence of pathologic nodal involvement, and thus need for a PLND? Results from the OSPREY trial suggest that the sensitivity of PSMA PET for the detection of positive LNs is only 40%,3 which was also confirmed in a large phase 3 trial of 277 intermediate/high risk patients (sensitivity: 40%, NPV: 81%).4
Clinicians performing a pelvic lymphadenectomy should perform an extended dissection, which improves staging accuracy compared to a limited dissection. (Moderate Recommendation; Evidence Level: Grade: B) A standard (i.e., limited) dissection includes the obturator +/- external iliac LNs. An extended template additionally includes the internal iliac +/- common iliac LNs.
For patients with positive lymph nodes identified at radical prostatectomy, clinicians should risk stratification based on pathologic variables and postoperative PSA. (Expert Opinion) Clinicians may offer patients with positive lymph nodes identified at radical prostatectomy and an undetectable post-operative PSA adjuvant therapy or observation. Based on institutional retrospective data, it appears that the 5-year BCR-free survival rate is 25-30%, with improved outcomes in patients with limited pathologic nodal involvement.
Based on evidence from the ARTISTIC collaboration and others, Clinicians should not routinely recommend adjuvant radiation therapy after radical prostatectomy. (Strong Recommendation; Evidence Level: Grade A)
Moving on to the principles of radiation, in patients with low- or favorable intermediate-risk prostate cancer electing radiation therapy, clinicians should not routinely use ADT due to the excellent observed outcomes with RT monotherapy in these patients. (Moderate Recommendation; Evidence Level: Grade B) Conversely, 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, largely based on the results of the EORTC 22991 trial in this setting6 (Strong Recommendation; Evidence Level: Grade A)
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, with results from the EORTC 22863 trial demonstrating an overall survival HR of 0.60 (95% CI: 0.45 – 0.80). (Strong Recommendation; Evidence Level: Grade A)
With regards to focal/whole gland ablation, 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) Clinicians should not recommend whole gland or focal ablation for patients with high-risk prostate cancer outside of a clinical trial. (Expert Opinion)
With regards to the management of patients with limited life expectancy, 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) Clinicians may recommend palliative ADT alone for patients with high-risk prostate cancer, local symptoms, and limited life expectancy. (Expert Opinion).
For post-treatment follow-up, clinicians should monitor patients with prostate cancer post therapy with PSA and symptom assessment. (Clinical Principle) Clinicians should support patients with prostate cancer through continued symptom management and encouraging engagement with professional or community-based resources.
Presented by: Stephen Boorjian, MD, Carl Rosen Professor and Chair of the Department of Urology, Mayo Clinic, Rochester, MN
Written by: Rashid K. Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 American Urological Association (AUA) Annual Meeting, Chicago, IL, April 27 – May 1, 2023
References:- Hamdy FC, et al. Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer. N Engl J Med, 2023.
- Briganti A, et al. Updated nomogram predicting lymph node invasion in patients with prostate cancer undergoing extended pelvic lymph node dissection: the essential importance of percentage of positive cores. Eur Urol, 2012.
- Pienta KJ, et al. A Phase 2/3 Prospective Multicenter Study of the Diagnostic Accuracy of Prostate Specific Membrane Antigen PET/CT with 18F-DCFPyL in Prostate Cancer Patients (OSPREY). J Urol, 2021
- Hope TA, et al. Diagnostic Accuracy of 68Ga-PSMA-11 PET for Pelvic Nodal Metastasis Detection Prior to Radical Prostatectomy and Pelvic Lymph Node Dissection: A Multicenter Prospective Phase 3 Imaging Trial. JAMA Oncol, 2021.
- Vale CL, et al. Adjuvant or early salvage radiotherapy for the treatment of localized and locally advanced prostate cancer: A prospectively planned systematic review and meta-analysis of aggregate data. Lancet, 2020
- Bolla M, et al. Short Androgen Suppression and Radiation Dose Escalation in Prostate Cancer: 12-Year Results of EORTC Trial 22991 in Patients With Localized Intermediate-Risk Disease. J Clin Oncol, 2021.
- Eastham JA, et al. Clinically localized prostate cancer: AUA/ASTRO guideline, part I: introduction, risk assessment, staging, and risk-based management. J Urol, 2022.