Knowledge of the natural spread of prostate cancer is crucial for determination of reasonable clinical target volumes. The most comprehensive data on this issue can be derived from pathological studies. The tumor-related bottleneck factors for CTV definitions are (a) the presence of extracapsular extension (ECE) and (b) seminal vesicle invasion (SVI).

In 1997 D’Amico et al. found in a retrospective analysis of 749 prostatectomy specimens that the risk of pathologic SVI as well as macroscopic extracapsular tumor extension is only 2 % in low-risk patients. They furthermore found that the risk of PSA relapse is similar in patients undergoing radical prostatectomy or radiotherapy when patients without clinical risk factors were included (D’Amico et al. 1997b). These factors were defined as PSA <10 ng/ml, clinical stage <T2c, and Gleason score <7, respectively. Further pathological studies confirmed these results (Kestin et al. 2002). Taking these findings into account, there is no sensible reason to include the seminal vesicles into the CTV in patients with low-risk prostate cancer. As the risk of ECE is similarly low, it is obvious to delineate the prostate only as CTV defined by the visible boundaries on planning computed tomography or magnetic resonance imaging. An example of CTV delineation is shown in Fig. 14.1b.

To shed light on this question, it is useful to focus on the two most relevant factors of tumor recurrence after definitive therapy, namely, extracapsular tumor extension and seminal vesicle involvement. It is well understood that the risk for these factors rises with increasing clinical risk factors. The question whether the degree of extracapsular extension may influence treatment outcome has been addressed by many authors. Just recently van Veggel published an outcome study after radical prostatectomy, focusing on the associated pathological ECE evaluation. Evaluation of the biochemical relapse rate of 134 patients according to different definitions of ECE revealed a significant association of the extent of ECE with the rate of biochemical relapse rates (van Veggel et al. 2011). Their results confirmed studies from various other authors (Epstein et al. 1993; Wheeler et al. 1998; Davis et al. 1999). To be able to apply these results to target volume definition in prostate cancer radiotherapy, it is necessary to evaluate the specific amount of extracapsular tumor extension. In the largest published series, Teh et al. found that, among all prostatectomy specimens with extracapsular tumor extension, only 2.8 % show an extension of more than 5 mm from the capsule (Teh et al. 2003). Several pathological studies have confirmed that more than 90 % of all patients who present with ECE have a radial tumor extension from the capsule of less than 4–5 mm (Davis et al. 1999; Schwartz et al. 2007; Sohayda et al. 2000).

CTV definition of the prostate gland plus an additional circumferential margin of 5 mm would thus cover more than 90 % of tumor extensions outside the prostate. At the prostate–rectum interface, the anterior rectal wall represents a solid boundary for tumor cells so that the CTV can be reduced posteriorly. An example is shown in Fig. 14.2.

Kestin and colleagues reviewed 344 prostatectomy specimens with regard to SVI. They found that the tumor never involves the whole SV; the most distant cancer found was 1.5 cm apart from the SV tip. Including the proximal 2 cm of the SV into the CTV would include 90 % of pathologically involved seminal vesicles. In terms of certainty of CT definitions of the seminal vesicle compared to pathological measurements, they furthermore found that the two methods are in good agreement (Kestin et al. 2002). Given that 38 % of all patients showed at least one high-risk feature, it seems advisable to include the proximal 2.0–2.5 cm of the seminal vesicles into CTV in order to cover more than 90 % of all SVI. Finally only 1 % of low-risk patients had an SVI which confirms not to include SVs into CTV in this patient group. With each prognostic high-risk factor, the rate of SVI rises from 15 % with one high-risk factor, 28 % with two, to 58 % with three high-risk factors, respectively.

With regard to CTV definition, it may be reasonable to include the base of the seminal vesicles (proximal 2–2.5 cm) into the CTV for all patients with high-risk features. Yet one must be aware that with only one high-risk factor the number of patients who are treated with a larger CTV without having an SVI is considerably high. The treating physician must refer to the available data to gain informed consent with the patient.