MR has a better diagnostic yield than TRUS and allows an evaluation of pelvic lymph node and bone status, with the detection of all sites of pelvic relapse in a single examination.

The administration of MR contrast medium, i.e., gadolinium, seems to improve further the overall accuracy. It theoretically allows detection of cancerous tissue in cases where morphological anomalies are not evidenced on unenhanced MR images and differentiation between tumor relapse and postoperative fibrosis or scar tissue.

MRI and dynamic contrast-enhanced MRI (DCE-MRI) can identify different site of local recurrence: VUA (52 %), retrovesical space (20 %), bladder neck (16 %), and circumferential areas (12 %).

Recurrences were, in most cases, slightly hyperintense to internal obturator muscle on T2-weighted sequences as found by Sella et al. [32] and in fewer cases markedly hyperintense on T2-weighted sequences.

Nodules that appear slightly hyperintense or markedly hyperintense on T2-weighted sequences may represent not only recurrences but also prostatic or seminal vesicle residues with different amounts of fibrosis.

The peri-anastomotic fibrosis appears hypointense on T2w images, with absent enhancement on DCE-MRI images (Fig. 27.1). After DCE-MRI, all benign nodules showed signal enhancement of less than 50 % in the early phase, whereas all recurrences showed fast signal enhancement in the early phase followed by plateau or washout. Recurrences appear as lobulated masses with intermediate signal intensity on T2w images, enhancing after intravenous injection of contrast medium (Fig. 27.1).

Silverman et al. [33] have achieved a high sensitivity and specificity (100 %) evaluating a group of patients with T1- and T2-weighted sequences and T1-weighted images with fat-suppression technique after gadolinium administration. All nodules showed signal enhancement after gadolinium administration, strengthening the suspicion that they were recurrences.

Also Sella et al. [32] have achieved a high sensitivity (95 %) and specificity (100 %) using T1- and T2-weighted sequences. All the local recurrences seen on MR images were isointense on T1-weighted sequences and slightly hyperintense to muscle on T2-weighted sequences. However, in the Sella study, the mean PSA level was 2.1 ng/ml, and in the Silverman study, 74 % had palpable recurrence and 88 % had a PSA >0.4 ng/ml; there would not have been any need of MRI to detect these recurrences. Therefore, the clinical benefit of current imaging is very low.

Casciani et al. [34] reported that MRI alone showed a poorer accuracy in detecting recurrences, probably due to the smaller size (between 0.4 and 3.0 cm) of the recurrences compared with those in the study of Silverman and the study of Sella et al. (0.7–3.8 cm and 0.8–4.5 cm, respectively). This comparison showed a statistically significant lower diagnostic accuracy of unenhanced eMR in comparison to CE-eMR (70 vs. 86 %), a statistically significant lower sensitivity (60 vs. 84 %) and no significant specificity differences (82 % vs. 89 %). Cosciani et al. [34] have supported the accuracy of eMR after RP providing high sensitivity of 84 % and specificity of 89.3 %, in patients with high PSA levels.

Recently, great interest has been shown to anatomic T2w imaging with functional MRI techniques such as DCE-MRI, DWI, and MR with spectroscopic imaging. In particular, DCE-MRI is useful for differentiating fibrosis in the prostatectomy fossa, remnants of normal prostatic tissue, and hyperplastic nodules from prostate cancer recurrence. DWI increases the accuracy of DCE-MRI well correlating with tissue cellularity of malignant tumors of the prostate.

In conclusion, MRI has proved to be useful at PSA values (generally higher than 1 ng/ml) for which the identified recurrence after RP cannot be treated with success.

Furthermore, MRI showed a limited clinical benefit in early diagnosis of recurrence after surgery since the lower detection limit is above 0.5 cm.

Improvement about the detection of local recurrence may be reached by employing an imaging technique based on metabolism rather than an anatomic imaging technique. In this respect, PET may play a role, with the use of different tracers [35].

Few studies [36–51] have reported on the detection of local recurrence after RP with ¹⁸F-fluoro-2-deoxy-D-glucose (¹⁸FDG). Its use in PCa is limited by a low sensitivity. There is a modest glucose consumption by PCa cells, and the uptake of this medium in the recurrent tumor has been shown to be similar to the uptake in postoperative scar or benign prostate tissue. Moreover, ¹⁸FDG is highly excreted into urine. Thus, results have been particularly disappointing for the diagnosis of recurrences.

Promising results in the detection of recurrent PCa have been obtained with the newer PET tracers: ¹¹C-acetate, ¹¹C-choline (Ch-PET), and ¹⁸F-fluorocholine. Since Ch-PET is not rapidly excreted in urine, Ch-PET show clear images of the pelvic region and of the PCa and pelvic lymph node metastases in the absence of urinary radioactivity.

Generally, Ch-PET provides good sensitivity and specificity values in detecting distant and local recurrences after RP and RT, but only in patients with high PSA levels.

Only few studies have assessed the accuracy of PET in RP patients with low PSA values; most of them report a low sensitivity of PET in detecting local recurrence. In a recent study, also Vees et al. [52] did not recommended Ch-PET as a standard diagnostic tool if early relapse is suspected because the high levels of PSA (<1 ng/ml) needed to detect local residual or recurrent disease after RP in about half the patients.

Recently, Heinisch et al. [53] have recommended using a ¹⁸F-fluorocholine PET/CT at PSA levels of >5 ng/ml. By contrast, de Jong et al. have reported that Ch-PET cannot be used to visualize prostate cancer on restaging at a PSA level of <4.5 ng/ml. Rinnab et al. [54] recommend using PET, even at PSA levels of <2.5 ng/ml, because early detection of recurrence can be an advantage for patients with increasing PSA levels.

In integrated PET/CT (computed tomography), the focal uptake of choline can be more easily assigned to anatomical structures, with a better differentiation of physiological (rectum and bladder) uptake from residual/recurrent PCa, resulting in a higher accuracy.

Moreover, with respect to conventional imaging techniques, the most important advantage is the staging of the disease in one step. Rinnab et al. have reported an overall sensitivity and positive predictive value of 95 and 86 %. The overall specificity was 40 % with a negative predictive value of 67 %.

In conclusion, Ch-PET detection rate of recurrences increases together with the increase of PSA serum value, and, according to the current available data, the use of choline PET/CT cannot be recommended for PSA values lower than 1 ng/ml.

Diagnosing local recurrence after radiotherapy (RT) is challenging because of radiation-induced fibrosis and shrinkage of the prostate. The sensitivity and specificity of TRUS are reported to be 49 % and 57 %, respectively [55]. Prostate cancer visualization by MRI is also critical, because the tissue contrast between recurrent cancer and benign irradiated tissue is decreased as the recurrent cancer after radiation therapy demonstrates low signal intensity on T2w imaging [56].

Results for T2w imaging at 3 T using a phased-array coil showed a poor diagnostic performance in predicting recurrent cancer in patients with biochemical failure after radiation therapy [57].

DCE-MRI can predict locally recurrent cancer more accurately than T2w imaging showing a hypervascular area within the slow/low enhancement of postradiation fibrosis. DWI added to MRI examination protocol increases the accuracy of the technique showing focal low signal intensity relative to the surrounding prostate tissue on ADC maps [57].

After RT, MR spectroscopy imaging demonstrates intraprostatic voxels with no detectable peaks for choline, polyamines, creatine, and citrate (so-called metabolic atrophy). However, residual prostate cancer can still be identified by a relative increase in the (choline + creatine)/citrate ratio or by an increase in the choline peak with no detectable citrate.

Using these criteria, good correlations between spectroscopic data and biopsy findings have been reported [58]. However, for unclear reasons, some benign glands can exhibit high levels of choline after RT and cause false-positive findings [59].

The use of choline PET/CT can be recommended since local recurrence after RT is associated with PSA values greater than 2 ng/ml (Fig. 27.2).

Cryotherapy (CT) of the whole prostate is widely used as primary treatment or salvage treatment for local recurrence after radiation therapy. Focal CT has been considered an investigational procedure in well-selected patient cases as alternative to achieve surveillance or total treatments (surgery or radiation or total CT). Role of imaging to detect local recurrence after total cryoablation is very limited. Absolute PSA levels (>0.5 ng/ml) or PSA kinetic (ASTRO or Phoenix definitions) is widely used and may predict recurrence [62]. B-mode transrectal ultrasound (TRUS) has a low diagnostic accuracy of local recurrence for several pitfalls: (1) isoechoic cancer, (2) posttreatment modifications, and (3) small-volume recurrent cancer. All these pitfalls explain also the limited value of TRUS. The goal of prostate CT is to produce complete necrosis of the prostate glands. Difficulty arises in the evaluation after total CT, because of the large damage zone, created by the treatment. In particular areas located at the margins of the ice ball (anterior zone, far basal zone close to seminal vesicles, distal apical tissue, periprostatic urethra, or subcapsular tissue) may persist a thin rim of untreated tissue (Fig. 27.3) or cancer [61]. These small areas may remain undetected by imaging techniques because of their irregular shape and volume (less than 5 mm) that also could be under the detection limits of MR.

New ultrasound (US) functions and magnetic resonance (MR) applications have the potential to enhance visualization of the residual prostate tissue and local recurrence. Contrast-enhanced US is a useful tool to detect untreated areas but no studies have been reported so far. Elastosonography [63] is not useful after CT since scar tissue and dense fibrosis are seen as hard tissue mimicking tumor. Color Doppler ultrasound may help in the detection of areas with residual vasculature.

There is a strong correlation between magnetic resonance imaging with gadolinium defects and amount of coagulation and necrosis caused by CT. However, gadolinium defects were not seen in areas of viable tissue as determined by histopathologic evaluation [64]. Some investigators reported that findings of postoperative gadolinium enhancement MR were not predictive of six-moth biopsy results or following PSA levels [65].

High-intensity focused ultrasound (HIFU) is a minimally invasive treatment for prostate cancer. Recommendations concerning HIFU in international guidelines are still conflicting [70, 71].

The overall quality of references about local recurrence is generally low because of small series, absence of pre-HIFU study, different timing in the scheduled posttreatment evaluation (1, 3, or 6 months), and generally retrospective evaluation of the results.

TRUS has a limited utility in patients treated with HIFU, since the gland appears diffusely heterogeneous after treatment. Conventional transrectal ultrasound (TRUS) is useless in identifying areas suspected for local recurrence, and even elastography was unable to precisely correlate with biopsy results. Color Doppler can improve recurrent cancer detection by guiding the biopsies towards hypervascular foci, but only 38 % of the sites with recurrent cancer show positive Doppler findings [72]. False-positive results are mostly due to residual benign tissue [73].

MRT2w imaging is difficult to interpret after HIFU ablation, because the gland is heterogeneous and diffusely hypointense. However, recurrent cancer can be visible in some patients as a nodular hypointense lesion [74]. Recurrent cancers are easier to distinguish from post-HIFU fibrosis using DCE imaging [75]. MRSI has been evaluated in few cases of patients, and it has shown to add no additional information than T2w imaging [74]; furthermore, when MRI is used as an indicator or residual viable tissue, it is very difficult to precisely match suspected areas at MRI with ultrasound-guided biopsy [76]. Again, the diagnosis of a local recurrence in this setting is based on the PSA values and PSA kinetics as well as the biopsy of the residual prostate after 12–18 months from treatment.