American Radium Society Appropriate Use Criteria for the Workup and Treatment of Local Intraprostatic Recurrence of Prostate Cancer Following Definitive Radiotherapy.

Background and objective: Local intraprostatic radiorecurrence of prostate cancer (IPR-PC) can be associated with an aggressive natural history and impact long-term disease-specific survival. While appropriate local salvage intervention can be curative, best practices for workup and local salvage of intraprostatic recurrence are poorly defined. The American Radium Society (ARS) Genitourinary Appropriate Use Criteria Committee sought to develop evidence-based recommendations to address this gap.

Methods: PubMed and Embase were searched to retrieve a comprehensive set of relevant peer-reviewed articles on four topics relevant to the workup and treatment of IPR-PC. The literature was evaluated and summarized by three investigators, and clinical variants were created for each of the four topics. The ARS Genitourinary AUC multidisciplinary expert panel voted on the most appropriate procedures for each variant, and a modified Delphi approach was used to summarize recommendations.

Key findings and limitations: The panel concluded that radiographic staging via prostate-specific membrane antigen positron emission tomography (PSMA PET) and multiparametric magnetic resonance imaging should be performed to exclude patients with metastatic disease and identify the local extent of radiorecurrence. Biopsy is required before local salvage to avoid excessive toxicity in patients whose radiographic recurrence represents a treatment effect. Consideration of local salvage is preferred in lieu of noncurative hormonal manipulation alone, although shared decision-making is critical. Salvage reirradiation approaches are recommended to limit toxicity. Hormonal therapy may be beneficial for radiosensitization when radiotherapeutic salvage is pursued, but only of short duration, and classic androgen deprivation therapies are preferred over novel hormonal agents. Focal salvage should be pursued when confidence in focal recurrence can be confirmed via multiple radiographic and tissue sampling modalities, although the toxicity associated with whole-gland salvage appears to be very tolerable. Several radiotherapeutic salvage regimens exist, most of which can be carried out in six or fewer fractions. The data informing this guideline are limited to individuals initially treated with conventionally fractionated external beam radiotherapy and with workup for recurrence before the PSMA PET era.

Conclusions and clinical implications: This consensus guideline provides evidence-based guidance on the appropriate procedures for workup and treatment of IPR-PC. Prospective evidence to enrich these guidelines is eagerly anticipated.

Patient summary: We summarize evidence for the best workup and treatment for patients with local recurrence of prostate cancer after radiotherapy. A panel of experts evaluated previous studies and voted on the procedures that should be performed and those that should be avoided. This guideline is a useful tool for helping doctors to discuss the best treatment options that maximize the chance of cure while minimizing side effects.