NCCN Reverses Guideline Recommendation, States Active Surveillance Is Preferred Option for Low-Risk Prostate Cancer

Following a change in September to the National Comprehensive Cancer Network (NCCN)’s recommendation for the use of more aggressive treatment interventions in addition to active surveillance for those with low-risk prostate cancer, the organization has reversed their decision with a degree of alteration.

Instead, the guidelines now suggest that the majority of men with low-risk disease be offered active surveillance as the only preferred treatment strategy, aligning with the NCCN’s decade long recommendation. In September, the organization had changed its long-standing treatment recommendation for low-risk patients and instead recommended the use of active surveillance, radiation therapy, or surgery for the population.

Currently the guidelines recommend that those who are at very low risk undergo multi-parametric MRI with or without biopsy, with all patients undergoing confirmatory prostate biopsy within 1 to 2 years of diagnosis. Low-risk patients have similar initial recommendations for clinically localized disease, with the additional recommendation of molecular tumor analysis if an MRI is not performed. Those in the intermediate-risk group have the previous recommendations plus bone and soft tissue imaging. Both high- and very high-risk patients should undergo both bone and soft tissue imaging.

In the very low-risk group with a life expectancy of over 20 years, active surveillance is the preferred treatment strategy, with other options including external beam radiotherapy or brachytherapy, and radical prostatectomy. However, active surveillance is an option that is "preferred for most patients" in the low-risk group whose life expectancy is 10 years or higher, who can receive the same alternative adjuvant treatment options as the very low-risk group. The recommended adjuvant therapy options for patients with favorable intermediate-risk prostate cancer include active surveillance, radiotherapy, and surgical interventions. An equal emphasis was placed on active surveillance, radiotherapy or brachytherapy, and radical prostatectomy with or without pelvic lymph node dissection in the intermediate-risk group whose life expectancy is over 10 years. Further intervention among those receiving surgery will be determined based on prostate-specific antigen (PSA) levels.

Surgery and radiotherapy are the recommended interventions for those in the unfavorable intermediate-risk group with a life expectancy of over 10 years, with similar recommendations for patients who are categorized as high- or very high–risk with a life expectancy of over 5 years. Patients with regional risk who are expected to survive for over 5 years are recommended to receive radiation therapy or androgen deprivation therapy (ADT) as the preferred interventions, with other options including ADT with or without abiraterone (Zytiga) and radical prostatectomy plus pelvic lymph node dissection.

In terms of monitoring following initial definitive therapy, PSA should be checked every 6 to 12 months for 5 years followed by every year thereafter. Digital rectal exams are recommended annually but can be omitted if there is no detectable PSA. In the event of radiographic evidence of metastatic disease plus or minus persistent or recurrent PSA, biopsy of the metastatic site is recommended. Among those with N1 disease who are being treated with ADT or those with localized disease who are under observation should receive a physical exam with PSA testing every 3 to 6 months. Imaging for symptoms or increasing PSA is also recommended.

The NCCN Prostate Cancer Panel and Prostate Cancer Early Detection Panel both continue to have concerns regarding the overdiagnosis and treatment of patients with prostate cancer, according to the guideline's Principles of Active Surveillance and Observation. Recommendations from the Prostate Cancer Panel state that patients and physicians should consider the possibility of active surveillance carefully based on the patient's risk profile and life expectancy. Among patients whose comorbidities and age may suggest a shorter life expectancy, observation may be the preferred option. The principles emphasize that shared decision making after the necessary counseling on risks and benefits of different treatment options is a critical part of the treatment process.

Confirmatory testing has been put in place to determine whether or not active surveillance is appropriate or not. As initial biopsy may underestimate a tumor's grade or volume, the NCCN strongly recommends confirmatory testing within the first 6 to 12 months following diagnosis in patients who may undergo active surveillance. Confirmatory testing may include prostate biopsy, multi-parametric MRI with PSA density calculation, and/or molecular tumor analysis. Additionally, the organization stated that confirmatory testing may not be necessary among those who have received a multi-parameter MRI prior to their diagnostic biopsy. Confirmatory biopsy should take place within 1 to 2 years of diagnostic biopsy.

Patients who choose to receive active surveillance need to receive several types of follow-up testing. PSA testing should take place no more than every 6 months unless otherwise indicated and digital rectal exam should occur no more than every 12 months. Repeat biopsy of the prostate should not happen more than every 12 months, although the intensity of surveillance can be customized based on the patient. Additionally, multi-parameter MRI shouldn't be performed more than every 12 months.

Patients with a suspicious lesion detected via multi-parameter MRI should receive MRI-US fusion biopsy, which can improve the detection of higher-grade tumors. Patients who have a life expectancy of less than 10 years should be transitioned to observation. The use of repeat molecular tumor analysis is not recommended and the intensity of surveillance should be tailored based on life expectancy and reclassification of risk.

Reference

NCCN. Clinical Practice Guidelines in Oncology. Prostate cancer version 2.2022. Accessed December 3, 2021. https://bit.ly/3luAd3q