Learning Objective

At the conclusion of the activity, participants will be able to highlight recent guideline updates in management of clinically localized prostate ­cancer.

Prostate cancer remains the most common noncutaneous cancer among U.S. men, with an estimated 268,490 new cases and 34,500 deaths in 2022.¹ The majority of newly diagnosed patients have clinically localized disease.¹ Providing evidence-based guideline statements to support clinical decision making represents an important component of delivering high-quality care. Given the recent breadth of investigation into various aspects of the evaluation and management of clinically localized prostate cancer (CLPC), the AUA, in collaboration with ASTRO (American Society for Radiation Oncology), updated the organization’s prior guideline. The 2022 iteration was presented at the 2022 AUA Annual Meeting as an Instructional Course, which summarized current evidence and provided specific guidance for physicians in the management of CLPC.

A critical component of the Guidelines is the recognition that the selection of a management strategy for CLPC is preference-sensitive and includes patients’ interpretation of treatment-specific risks and benefits. The Guidelines thereby emphasize a collaborative, shared decision-making (SDM) process. In addition, the Guidelines includes specific guidance on risk assessment and staging, risk-based management, principles of active surveillance (AS), surgery, and radiation, and recommendations for followup after treatment.²

Risk Assessment and Staging

An important component of the updated Guideline is the continued utilization of a risk group classification for patients with newly diagnosed CLPC. The intention of risk stratification is to facilitate patient counseling regarding the severity of disease and documented natural history. Such perspective facilitates SDM, to allow consideration of the tradeoffs between treatment-related side effects and the likelihood of disease progression. Furthermore, determining disease risk informs the intensity of the staging evaluation, management options, and allows assessment of clinical trial eligibility.

While recognizing that risk groups may be updated as new information is gained, the current Guideline risk group criteria include the clinical T stage (determined by digital rectal examination [DRE]), serum PSA, Grade Group (Gleason score), and tumor volume on biopsy (see Table).

Imaging studies are intended to define the local extent of disease as well as determine the presence of nodal and distant metastases, and thereby inform management. As such, clinicians should use a risk-based approach to staging for patients with newly diagnosed prostate cancer.

Risk-Based Management

Outlining the likelihood of both cancer control and the recognized risks or side effects associated with each management strategy for CLPC facilitates SDM. Indeed, tools are available to estimate the likelihood of ­functional outcomes with each treatment.³ The Guidelines provide risk-based recommendations for management, with ­strategies mentioned including AS, surgery, radiation, ablation, and systemic therapy. The Guideline further discusses appropriate patient selection for watchful waiting, a strategy that does not involve routine cancer surveillance, but rather aims to deliver palliative therapy for relief of symptoms should they develop. Watchful waiting is appropriate for asymptomatic elderly patients or patients with significant comorbidities in whom competing risks of mortality are considerably greater than the risk of death from prostate cancer.

Table. Risk group classification

Principles of AS

While AS is the preferred management option for most low-risk patients, those electing this option need to be counseled regarding the importance of continued followup as part of this approach. Specifically, patients on AS should undergo PSA testing (no more frequently than every 6 months), updated symptom assessment, and physical examination with DRE every 1 to 2 years. Serial PSA increases, new DRE abnormalities, or other concerns for clinical progression should prompt reevaluation with MRI and possible prostate biopsy; less frequently, direct conversion to treatment may be considered. Importantly, the Panel believes that while multiparametric MRI may be used to augment risk stratification for patients managed with AS, MRI should not replace periodic surveillance biopsies.

Principles of Surgery

While several recommendations regarding surgery remain unchanged from previous Guideline iterations, the 2022 Guideline was informed by inclusion of greater followup data as well as further discussion of pelvic lymphadenectomy. For example, the Guideline advises the use of nomograms to select patients for pelvic lymphadenectomy.⁴ In addition, when the decision is made to perform pelvic lymphadenectomy, the Panel recommends an extended lymph node dissection because of its incremental staging benefit versus a limited dissection.⁵ At the same time, the updated Guideline also acknowledges that while pelvic lymphadenectomy is useful for staging and may provide valuable information to guide future management with secondary therapies, an oncologic benefit to lymphadenectomy has not been well established.^6,7 Indeed, to date, randomized studies have not compared the relative oncologic outcomes among patients undergoing extended lymph node dissection (performed according to a standardized template) at the time of prostatectomy versus patients undergoing no lymph node dissection at the time of prostatectomy specifically in a high-risk cohort.

Principles of Radiation

As with surgery, many statements regarding radiation remain unchanged from the previous Guideline iteration; however, the new Guideline does provide detailed discussion of options for men with higher-risk disease, which may include newer forms of radiation therapy and details regarding the indications for combination with androgen deprivation therapy (ADT).

In looking at the role of lymph node irradiation among patients electing radiation therapy, the Guideline notes the lack of benefit in low- and intermediate-risk patients from prospective trials. At the same time, based on recent trial data, the Guideline does state that nodal radiation may be offered to high-risk patients.^8,9 Indeed, inclusion of pelvic lymph nodes in the radiation field has been associated with improvements in biochemical recurrence and distant metastases. The Panel recognizes that while previous trials did not demonstrate a benefit to nodal radiation, many of those studies were limited by variably defined high-risk subgroups, use of simpler radiation technologies with more limited pelvic fields, shorter durations of ADT, and delivery of lower radiation doses to the prostate.

Importantly, the Guideline highlights the judicious use of ADT with radiation by outlining risk-based indications for and duration of ADT among patients electing radiation therapy. Indeed, the well-recognized adverse effects of ADT, which in turn may potentially negatively impact patients’ quality of life, must be considered. As such, the Panel believes that patients being offered ADT should be aware of these side effects.

Follow-up after Treatment

Monitoring after treatment is necessary to identify recurrence as well as complications from treatment, and thereby facilitate early intervention as appropriate. The Panel therefore included recommendations regarding initial and ongoing monitoring and highlighted the importance of routine discussion of urinary, bowel, and sexual function with the use of standardized/validated instruments.

Further, it was acknowledged that clinicians should also support patients with CLPC through continued symptom management and encourage engagement with professional or community-based resources. The array of survivorship needs for an individual patient and caregiver may be broad and should be explored by the clinician and team to ensure that appropriate support, especially peer support, is offered.