Historically, the prostate was treated with four static radiation fields designed based on anatomic landmarks. However, with this technique, it is difficult to get idea about the target volume doses and also surrounding organs. As a consequence, geographic misses may be seen more than expected, and it is difficult to know about the toxicities. With the use of a 3D conformal RT (3DCRT) technique, the dose escalation above 70 Gy resulted in a modest increase in rectal and bladder toxicity. With advancements in imaging, more focal three-dimensional treatment plans were developed to target the prostate and seminal vesicles only (Fig. 16.4). Further advances in radiation delivery techniques such as IMRT and volumetric modulated arc therapy (VMAT ) led to greater sparing of adjacent normal tissue to reduce toxicity. Techniques such as VMAT and IMRT are able to generate conformal isodoses, which significantly reduce the OAR doses and normal tissue toxicity [25]. Although IMRT is a commonly used method to treat prostate cancer, the potential downsides of IMRT include increased RT delivery time, resulting in a greater integral body dose, which might increase the risk of secondary cancer development [26].

VMAT is an innovative form of IMRT optimization that allows the radiation dose to be efficiently delivered using a dynamic modulated arc. The VMAT simultaneously coordinates gantry rotation, multi-leaf collimator (MLC) motion, and dose-rate modulation, facilitating highly conformal treatment with better normal tissue sparing [27]. Compared with IMRT, the potential advantages of VMAT include a large reduction in monitor units (MU) required to deliver a given fraction size and a concomitant reduction in treatment time (Figs. 16.5 and 16.6). Helical tomotherapy (HT) is an arc-based application of IMRT that uses a fan beam of radiation in conjunction with binary MLC. The gantry rotates at a constant speed, while the binary MLC leaves open 51 times per rotation and close entirely between projections. This rotational treatment modality can establish target dose conformity and OAR dose reduction (Fig. 16.7). Several recent studies have evaluated the use of VMAT delivery methods in prostate cancer (Table 16.1) [28–38].

Image guidance is essential for delivering the high radiation doses to the prostate accurately. The prostate is a mobile organ influenced by bladder and rectal filling. The position of these structures as defined on the planning CT can vary during and between fractions. Delivery of highly conformal treatments with steep dose gradients demands confidence in localization of the target because motion can lead to geographic miss, underdosing of the tumor, and/or unwanted overdosing of organs at risk. Dedicated CBCT equipment can acquire a 3D CT image in real time in the treatment position just before treatment (Fig. 16.8). Resolution is not of diagnostic quality but enables visualization of soft tissues (prostate, bladder, and rectum) so that table shifts can be made if needed. CBCT can be used in conjunction with fiducial seeds. However, the implantation of fiducial markers is an invasive procedure with the potential for discomfort, bleeding, and infection. Furthermore, fiducial markers provide little information on deformation of the target, localization of the seminal vesicles, or alteration in the neighboring normal tissue and may cause deformation of the prostate gland after implantation. Although fiducial marker implantation for image-guided RT in prostate cancer allows the localization of the prostate during treatment, this application may cause some complications and dosimetric uncertainties. Therefore, alternative noninvasive methods of CBCT should be considered for IGRT of prostate cancer patients [39].

External beam radiotherapy (EBRT) focusing on intensity-modulated RT (IMRT ) and image-guided RT (IMRT), hypofractionation and stereotactic body RT (SBRT), high-dose rate (HDR) brachytherapy, proton beam RT (PBRT), and ablative therapies such as cryoablation, high-intensity focused ultrasound (HIFU), and radiofrequency ablation (RFA) are therapeutic modalities that have been investigated in patients with PC in an attempt to reduce toxicity while improving cancer control. These treatment modalities could be used as monotherapy, whole prostate, or IPL boost.

A 3 mm thickness planning CT should cover the whole pelvis for RT planning. Patients need to be asked to have a comfortably full bladder and an empty rectum [40]. If MRI or PET fusion is planned to fuse with planning CT, these imaging modalities should be obtained in closest possible condition. In addition to that, in patients planning to receive androgen blockade, imaging should be preferred before the initiation of hormonal therapy [31]. Gross tumor volume (GTV), clinical tumor volume (CTV), and planning tumor volume (PTV) are basically defined in the International Commission of Radiation Units and Measurements (ICRU) [41]. CTV is based on clinical or pathological staging, while appropriate PTV margin is based on the RT technique and image guidance in the oncological center. The rectum, sigmoid colon, small bowels, bladder, and femoral heads are recommended to delineate as OAR. The rectum needs to be delineated from the anal verge to the rectosigmoidal junction. Femoral heads need to be delineated to the level of ischial tuberosities.

Dose escalation for prostate cancer causes improved biochemical control and reduced distant metastasis [2]. However, local failure still occurs in one-third of patients after 78 Gy ERT, and the original IPL is the most frequent location of relapse [42]. Therefore, selectively boosting radiation to these lesions to a very high dose has been hypothesized to be a more effective method to improve the therapeutic ratio than a homogeneous, but more modest, dose escalation to the entire prostate [43]. Randomized trials have shown a gain in BPFS using dose escalation for PC [1, 2]. However, isolated local failure is still reported in nearly one-third of patients, even with higher RT doses [2]. Local recurrence is of clinical importance because a relationship has been suggested between local control, distant metastasis, and survival [44]. Also, it has been demonstrated that local failure mainly originates at IPL. This could be a result of intrinsic resistance of radioresistant tumor clones [42]. So, delivering higher doses to IPL using SIB technique may potentially increase local control and treatment outcomes. The SIB technique can be safely performed by static IMRT , VMAT, or HT (Fig. 16.9). With VMAT plan (Fig. 16.10) and HT plan (Fig. 16.11), a homogeneous dose distribution was observed in target volumes with better sparing of the surrounding organs.

There are several studies investigating SIB boost to IPL/whole gland in treatment of PC [12, 32, 45–47] (Table 16.2). A boost to the IPL has been found to be effective and safe [48]. The reported BRFS and DFS rates were 78–92% and 90–100%, respectively [48]. Although SIB to IPL is not a standard approach, several ongoing studies will evaluate whether this approach is effective in local tumor control or not.

The investigate the benefit of a focal lesion ablative microboost in prostate cancer (FLAME) trial (ClinicalTrials.​gov identifier NCT01168479) is a phase III study evaluating an EBRT boost to the DIL [49]. The tumor TARGET PC trial is a nonrandomized phase II study (ClinicalTrials.​gov identifier, NCT01802242) comparing a combination of a boost to the DIL with high-dose-rate brachytherapy and a moderate dose of volumetric modulated arc therapy (VMAT ) for the rest of the prostate, with VMAT as monotherapy for the whole prostate.

Larger fraction per treatment is hypothesized with better radiobiological effect in the treatment of PC [50]. In addition to that, the potentially low alpha/beta ratio of PC is hypothesized as the rationale of hypofractionation and SBRT [51–53]. In moderate hypofractionation, 2.2–4 Gy per fraction is generally delivered with linear accelerators, while doses above 5 Gy are used in SBRT. SBRT uses more intensive immobilization and tracking systems to safely deliver high doses of radiation compared to IMRT .

SBRT and hypofractionation studies generally investigated low-risk and intermediate-risk patients. Because high-risk disease requires more comprehensive approach due to risk of regional spread, SBRT is generally used as boost in such patients. Also, greater likelihood of local recurrence and resistance of conventional RT dose makes high-risk patients a candidate for dose escalation with larger RT fraction [54].

Summaries of hypofractionation and SBRT studies are depicted in Table 16.3. Briefly, SBRT and hypofractionated RT could be used as monotherapy, whole-gland boost therapy, or focal boost of IPL. There are various RT schemes for monotherapy of PC, but the optimal fractionation has not been determined. Most of the studies investigated the BPFS, quality of life (QoL), and toxicity. In general, hypofractionation or SBRT is well tolerated with acceptable results without any serious increase in toxicity.