**8. Very low- and low-risk prostate cancer**

Patients with an NCCN risk-stratified very low- or low-risk prostate cancer and a life expectancy >10 years are usually recommended active surveillance (AS) [8]. This option involves obtaining a PSA no more often than every 6 months, DRE no more often than every 12 months, repeat biopsy no more often than yearly unless clinically indicated, and consideration of repeat mpMRIs no more often than every 12 months. Patients on AS are usually recommended curative-intent therapy if there is an increase in Gleason grade on repeat biopsy, tumor volume, or PSA density. Patient anxiety is also an important factor in management decisions, as patients may elect to come off of AS.

For patients with localized very low- or low-risk prostate cancer and a life expectancy of <5–10 years, observation ("watchful waiting") is generally recommended [8]. This process involves monitoring with a H&P and PSA no more often than every 12 months without biopsies until symptoms develop, or are thought to be imminent. Therapy is palliative only.

Per the NCCN guidelines, EBRT, proton therapy, SBRT, and brachytherapy monotherapy are potential radiotherapy treatment options for very low- and low-risk prostate cancer [8].

### **8.1 Favorable intermediate-risk (FIR) prostate cancer**

Patients with FIR prostate cancer and a life expectancy >10–20 years are usually recommended curative-intent therapy [8]. However, active surveillance may be offered if there are more favorable tumor characteristics, significant co-morbidities, poor urinary function, and/or strong patient preference; patient compliance is important if active surveillance is chosen.

Per the NCCN guidelines, EBRT, proton therapy, SBRT, and brachytherapy monotherapy are potential radiotherapy treatment options for FIR [8].

### **8.2 Unfavorable intermediate risk (UIR) prostate cancer**

UIR prostate cancer has been demonstrated to have an increased risk of pelvic and distant metastases versus FIR disease, and additional metastatic work-up is recommended, including either a CT abdomen/pelvis plus bone scan or alternatively a PSMA PET/CT [8, 9]. Treatment is recommended for those patients with >10 years life expectancy, while patients with <10 years are recommended observation. Brachytherapy may be offered as a boost, per the ASCENDE-RT trial, which demonstrated a significant difference at 10 years in biochemical disease-free survival, though no difference in OS and with more toxicities [29]; some researchers extrapolate that an overall survival (OS) difference may be reached with the passage of more time in this study.

Neoadjuvant, concurrent, and adjuvant short-term ADT is recommended in addition to radiotherapy in the form of a leutinizing hormone-releasing hormone agonist (e.g., goserelin or leuprolide) or antagonist (e.g., degarelix or relugolix) [8]. This recommendation is based on a modest but significant improvement in OS at 10 years in UIR patients receiving short-term ADT [30, 31]. ADT is usually initiated 2 months before RT, though the sequencing is subject to change. It is hypothesized that ADT radiosensitizes prostate cancer by decreasing non-homologous end-joining DNA repair, thereby acting synergistically with radiotherapy. ADT may also shrink the prostate and primary tumor, which may theoretically decrease the target volume and GI/GU toxicities. With combination EBRT/brachytherapy boost for UIR prostate cancer, short-term ADT may be omitted [8].

Per the NCCN guidelines, EBRT, proton therapy, SBRT, and combination EBRT/brachytherapy are potential radiotherapy treatment options for UIR [8].
