**7. Treatment for clinically localized disease**

Evaluation of prostate cancer begins with a history and physical (H&P), assessing for baseline urinary function (e.g., American Urological Association [AUA] score/ International Prostate Symptom Score [IPSS]); sexual function (Sexual Health Inventory for Men [SHIM] score); bowel function; and prostate abnormalities on digital rectal examination (DRE) such as enlargement, induration, nodularity, extracapsular extension, and/or invasion. PSA and velocity (doubling time) should be calculated, and a prostate biopsy should be obtained, if not already.

#### **7.1 Treatment options**

This chapter discusses radiotherapy options for prostate adenocarcinoma, and will not delve into radical prostatectomy/surgical options. Potential radiotherapy options include photon EBRT, proton EBRT, and brachytherapy; EBRT includes standard fractionation (about nine weeks), moderate hypofractionation (about 4–5 weeks), or SBRT (about 4–5 sessions, recommended every other day to reduce toxicities). Intensity-modulated radiotherapy/image-guided radiotherapy (IMRT/IGRT) is strongly recommended to enable dose escalation, while reducing genitourinary (GU) and gastrointestinal (GI) toxicities. Fiducial markers are strongly recommended for

### *Evaluation of Patients for Radiotherapy for Prostate Adenocarcinoma DOI: http://dx.doi.org/10.5772/intechopen.109447*

SBRT due to the extreme level of precision required and low number of fractions, and potentially for other EBRT treatments [8]; hydrogel spacers between the prostate and rectum may also be important for SBRT and brachytherapy to reduce the rectal dose, and in certain other EBRT cases [8].

Compared to conventional fractionation, moderate hypofractionation has demonstrated similar efficacy and toxicity in randomized trials, such as the CHHIP and PROFIT trials [18, 19]; however, some trials such as the HYPRO trial have demonstrated worse toxicity [20]. An ASTRO/ASCO/AUA evidence-based guideline concluded that hypofractionation is justified for routine use in this setting [21]. Common moderate hypofractionation regimens in the United States include 70 Gy/28 fractions, 70.2 Gy/26 fractions, and 60 Gy/20 fractions.

SBRT delivers highly-conformal, high-dose radiation in typically 4–5 fractions. Most of the data supporting SBRT are phase 2 trials demonstrating excellent biochemical progression-free survival and similar early toxicity to standard radiotherapy, but one phase 3 trial demonstrates non-inferiority of SBRT [22, 23]. Better candidates for SBRT have lower IPSS scores and prostates that are not significantly enlarged. SBRT with elective nodal irradiation is being explored, such as in the SATURN trial [24]. As well, SBRT is also being investigated as a neoadjuvant therapy before radical prostatectomy in high-risk patients, with phase I trials showing feasibility and safety, though one recent phase I trial assessing maximum tolerable dose was stopped early due to unacceptable toxicity [25, 26]. Additionally, some trials are looking at boosting the dominant intra-prostatic lesions to higher doses [27].

Brachytherapy monotherapy may be offered in the form of low-dose rate (LDR) or high-dose rate (HDR) brachytherapy. Alternatively, brachytherapy may be used as a boost after EBRT to 45–50.4 Gy for UIR, high-risk, and very high-risk prostate adenocarcinoma.

Proton radiotherapy has not demonstrated clear superior or inferior outcomes or differences in toxicity over photon radiotherapy, though one large Surveillance, Epidemiology, and End Results (SEER) study did demonstrate increased bowel toxicity [28]. Of note, proton therapy for prostate cancer is typically several times the cost of IMRT/IGRT treatments. The NCCN recommends proton therapy as a potential alternative to photon EBRT. Clinical trials are ongoing.
