Predictive factors of [11C]choline PET/CT in patients with biochemical failure after radical prostatectomy

Purpose

Detection of recurrence in prostate cancer patients with biochemical failure after radical prostatectomy by [¹¹C]choline PET/CT depends on the prostate-specific antigen (PSA) level. The role of other clinical and pathological variables has not been explored.

Methods

A total of 2,124 prostate cancer patients referred to our Institution for [¹¹C]choline PET/CT from December 2004 to January 2007 for restaging of disease were retrospectively considered for this study. Inclusion criteria were: previous treatment by radical prostatectomy, and biochemical failure, defined as at least two consecutive PSA measurements of >0.2 ng/ml. These criteria were met for 358 patients. Binary logistic analysis was used to investigate the predictive factors of [¹¹C]choline PET/CT. PET/CT findings were validated using criteria based on histological analysis, and follow-up clinical and imaging data. Receiver operating characteristic (ROC) analysis was used to assess the performance of [¹¹C]choline PET/CT in relation to PSA levels.

Results

The mean PSA level was 3.77?±?6.94 ng/ml (range 0.23–45 ng/ml; median 1.27 ng/ml). PET/CT was positive for recurrence in 161 of 358 patients (45%). On an anatomical region basis, [¹¹C]choline pathological uptake was observed in lymph nodes (107/161 patients, 66%), prostatectomy bed (55/161 patients, 34%), and in the skeleton (46/161 patients, 29%). PET/CT findings were validated using histological criteria (46/358, 13%), and follow-up clinical and imaging criteria (312/358, 87%). Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were, respectively, 85%, 93%, 91%, 87%, and 89%. In multivariate analysis, high PSA levels, advanced pathological stage, previous biochemical failure and older age were significantly (P?<?0.05) associated with an increased risk of positive PET/CT findings. The percentage of positive scans was 19% in those with a PSA level between 0.2 and 1 ng/ml, 46% in those with a PSA level between 1 and 3 ng/ml, and 82% in those with a PSA level higher than 3 ng/ml. ROC analysis showed that PET/CT-positive and PET/CT-negative patients could be best distinguished using a PSA cut-off value of 1.4 ng/ml.

Conclusions

In addition to PSA levels, pathological stage, previous biochemical failure and age should be considered by physicians when referring prostate cancer patients with biochemical failure after radical prostatectomy to [¹¹C]choline PET/CT.     

11C-Choline PET/CT in patients with hormone-resistant prostate cancer showing biochemical relapse after radical prostatectomy

Purpose

To determine the diagnostic efficacy of ¹¹C-choline PET/CT in patients with prostate cancer (PC) after radical prostatectomy who presented with increasing PSA levels during follow-up in spite of being on hormone treatment (HT), and therefore showing HT resistance.

Methods

We evaluated a large series of 157 consecutive PC patients previously treated by radical prostatectomy who presented with biochemical recurrence with increasing PSA levels in spite of ongoing HT (HT-resistant patients). At the time of ¹¹C-choline PET/CT, the mean value of trigger PSA level was 8.3 (range ?0.2 – 60.6 ng/mL), the mean PSA doubling time (PSAdt) was 5.3? (range ?0.4 – 35 months), and the mean PSA velocity (PSAvel) was 22.1 ng/mL/year (range 0.12 – 82 ng/mL/year). ¹¹C-Choline PET/CT was performed following a standard procedure at our centre to investigate increasing PSA levels, either as the first imaging procedure or in patients with negative conventional imaging. At the time of ¹¹C-choline PET/CT all patients were receiving HT (61 were receiving monotherapy and 96 multidrug therapy). PET-positive findings were validated by: (a) transrectal US-guided biopsy in patients with recurrence in the prostatic bed, (b) surgical pelvic lymphadenectomy, (c) other imaging modalities, including repeated ¹¹C-choline PET/CT, performed during a minimum follow-up of 12-months.

Results

¹¹C-Choline PET/CT showed positive findings in 104 of the 157 patients (66 %). ¹¹C-choline PET/CT detected: a single lesion in 40 patients (7 in the prostate bed, 10 in lymph nodes, 22 in bone, 1 at another site); two lesions in 18 patients (7 in lymph nodes, 7 in bone, 4 in both lymph nodes and bone); three or four lesions in 7 patients (4 in lymph nodes, 2 in bone, 1 at another site); and more than four lesions in the remaining 39 patients (2 in the prostate bed, 12 in lymph nodes, 12 in bone, 11 in both lymph nodes and bone, 2 at other sites). In ¹¹C-choline PET-negative patients, the mean values of trigger PSA, PSAdt and PSAvel were 3.8 ng/mL (range 0.2 – 11.9 ng/mL) 7.0 months (range 1.21 – 35 months) and 5.8 ng/mL/year (range 0.12 – 30.1) respectively, while in ¹¹C-Choline-PET-positive patients they were 10.5 ng/mL (range 0.2 – 60.6), 4.4 months (range 0.4 – 19.7) and 15.9 ng/mL/year (range 0.5 – 82.0) respectively. The differences between PET-negative and PET-positive patients were statistically significant for all these parameters: trigger PSA, p?<?0.01; PSAdt, p?<?0.01; PSAvel, p?=?0.03.

Conclusion

In our patient population, ¹¹C-choline PET/CT was able to detect relapsed disease in a large proportion of HT-resistant PC patients during HT. These data, obtained in a large series, suggest that HT withdrawal before performing a ¹¹C-choline PET/CT scan may not be necessary for the detection of recurrent disease if PSA levels are increasing and PSA kinetics are rapid.     

Comparison of integrated whole-body [11C]choline PET/MR with PET/CT in patients with prostate cancer

Purpose

To evaluate the performance of conventional [¹¹C]choline PET/CT in comparison to that of simultaneous whole-body PET/MR.

Methods

The study population comprised 32 patients with prostate cancer who underwent a single-injection dual-imaging protocol with PET/CT and subsequent PET/MR. PET/CT scans were performed applying standard clinical protocols (5 min after injection of 793?±?69 MBq [¹¹C]choline, 3 min per bed position, intravenous contrast agent). Subsequently (52?±?15 min after injection) PET/MR was performed (4 min per bed position). PET images were reconstructed iteratively (OSEM 3D), scatter and attenuation correction of emission data and regional allocation of [¹¹C]choline foci were performed using CT data for PET/CT and segmented Dixon MR, T1 and T2 sequences for PET/MR. Image quality of the respective PET scans and PET alignment with the respective morphological imaging modality were compared using a four point scale (0–3). Furthermore, number, location and conspicuity of the detected lesions were evaluated. SUVs for suspicious lesions, lung, liver, spleen, vertebral bone and muscle were compared.

Results

Overall 80 lesions were scored visually in 29 of the 32 patients. There was no significant difference between the two PET scans concerning number or conspicuity of the detected lesions (p not significant). PET/MR with T1 and T2 sequences performed better than PET/CT in anatomical allocation of lesions (2.87?±?0.3 vs. 2.72?±?0.5; p?=?0.005). The quality of PET/CT images (2.97?±?0.2) was better than that of the respective PET scan of the PET/MR (2.69?±?0.5; p?=?0.007). Overall the maximum and mean lesional SUVs exhibited high correlations between PET/CT and PET/MR (ρ?=?0.87 and ρ?=?0.86, respectively; both p?<?0.001).

Conclusion

Despite a substantially later imaging time-point, the performance of simultaneous PET/MR was comparable to that of PET/CT in detecting lesions with increased [¹¹C]choline uptake in patients with prostate cancer. Anatomical allocation of lesions was better with simultaneous PET/MR than with PET/CT, especially in the bone and pelvis. These promising findings suggest that [¹¹C]choline PET/MR might have a diagnostic benefit compared to PET/CT in patients with prostate cancer, and now needs to be further evaluated in prospective trials.     

[<Superscript>11</Superscript>C]choline PET/CT imaging in occult local relapse of prostate cancer after radical prostatectomy

Purpose The aim of this study was to assess the accuracy and clinical impact of [¹¹C]choline PET/CT for localizing occult relapse of prostate adenocarcinoma after radical prostatectomy. Methods Fourty-nine patients with prostate adenocarcinoma, radical prostatectomy, no evidence of metastatic disease, and occult relapse underwent [¹¹C]choline PET/CT. Thirty-six of the patients had biochemical evidence and histological evaluation of local recurrence. Thirteen patients had PSA < 0.3 ng/ml and no evidence of active disease after 1 year follow-up. Focal nodular [¹¹C]choline uptake in the prostatic fossa was visually assessed and graded on a five point scale. Maximum standardized radioactivity uptake value (SUV_max) and the lesion size were measured. A receiver operating characteristic (ROC) analysis was performed and the clinical impact of the PET/CT study was determined. Results [¹¹C]choline PET/CT was true positive in 23/33 patients and true negative in 12/13 controls. SUV_max of local recurrence was 3.0 (median, range 0.6–7.4) and 1.1 (0.4–1.6) in controls (p = 0.0002). Lesion size was 1.7 cm (range 0.9–3.7). Area under the ROC curve for detecting relapse was 0.90 ± 0.05 and 0.83 ± 0.06 for visual evaluation and SUV_max, respectively. Sensitivity and specificity of [¹¹C]choline PET/CT were 0.73 and 0.88, respectively. [¹¹C]choline PET/CT identified 12/17 (71%) patients with a favourable biochemical response to local radiotherapy at 2 year (median, 0.8–3.2 range) follow-up. Conclusions Focally increased [¹¹C]choline uptake in the prostatic bed reliably predicted local low volume occult relapsing prostate adenocarcinoma after radical prostatectomy and identified 71% of patients with a favourable biochemical response to local radiotherapy.     

[11C]Choline PET/CT detection of bone metastases in patients with PSA progression after primary treatment for prostate cancer: comparison with bone scintigraphy

Purpose  

The aim of this study was to evaluate the clinical usefulness of [¹¹C]choline positron emission tomography (PET)/CT in comparison with bone scintigraphy (BS) in detecting bone metastases (BM) of patients with biochemical progression after radical treatment for prostate cancer (PCa).     

Tumour volume delineation in prostate cancer assessed by [11C]choline PET/CT: validation with surgical specimens

Purpose

PET has been proven to be helpful in the delineation of gross tumour volume (GTV) for external radiation therapy in several tumour entities. The aim of this study was to determine if [¹¹C]choline PET could be used to localize the carcinomatous tissue within the prostate in order to specifically target this area for example with high-precision radiation therapy.

Methods

Included in this prospective study were 20 patients with histological proven prostate carcinoma who underwent [¹¹C]choline PET/CT before radical prostatectomy. After surgical resection, specimens were fixed and cut into 5-mm step sections. In each section the area of the carcinoma was delineated manually by an experienced pathologist and digitalized, and the histopathological tumour volume was calculated. Shrinkage due to resection and fixation was corrected using in-vivo and ex-vivo CT data of the prostate. Histopathological tumour location and size were compared with the choline PET data. Different segmentation algorithms were applied to the PET data to segment the intraprostatic lesion volume.

Results

A total of 28 carcinomatous lesions were identified on histopathology. Only 13 (46 %) of these lesions had corresponding focal choline uptake. In the remaining lesions, no PET uptake (2 lesions) or diffuse uptake not corresponding to the area of the carcinoma (13 lesions) was found. In the patients with corresponding PET lesions, no suitable SUV threshold (neither absolute nor relative) was found for GTV segmentation to fit the volume to the histological tumour volume.

Conclusion

The choline uptake pattern corresponded to the histological localization of prostate cancer in fewer than 50 % of lesions. Even when corresponding visual choline uptake was found, this uptake was highly variable between patients. Therefore SUV thresholding with standard algorithms did not lead to satisfying results with respect to defining tumour tissue in the prostate.     

Relationship between PSA kinetics and [18F]fluorocholine PET/CT detection rates of recurrence in patients with prostate cancer after total prostatectomy

Purpose

The aim of the present study was to identify prostate-specific antigen (PSA) threshold levels, as well as PSA velocity, progression rate and doubling time in relation to the detectability and localization of recurrent lesions with [¹⁸F]fluorocholine (FC) PET/CT in patients after radical prostatectomy.

Methods

The study group comprised 82 consecutive patients with biochemical relapse after radical prostatectomy. PSA levels measured at the time of imaging were correlated with the FC PET/CT detection rates in the entire group with PSA velocity (in 48 patients), with PSA doubling time (in 47 patients) and with PSA progression (in 29 patients).

Results

FC PET/CT detected recurrent lesions in 51 of the 82 patients (62%). The median PSA value was significantly higher in PET-positive than in PET-negative patients (4.3?ng/ml vs. 1.0?ng/ml; p?p?p?p?=?0.071).

Conclusion

In a study cohort of patients with biochemical recurrence of prostate cancer after radical prostatectomy there emerged clear PSA thresholds for the presence of FC PET/CT-detectable lesions.     

Prostate-specific antigen kinetics and choline PET/CT in patients with biochemical relapse after primary treatment for prostate cancer

Over the past few years, several studies have proved the potential role of diagnostic procedures in patients with treated prostate cancer who develop biochemical relapse. Notably, no precise indications exist regarding the use of emerging modalities such as positron emission tomography/computerized tomography (PET/CT) scanning with radiolabeled choline. However, the literature suggests that the main and most important application of choline PET/CT at present is in disease restaging in cases of biochemical relapse for the detection of local, lymph node-related or distant recurrence. In this setting, it is well known that prostate-specific antigen (PSA) values play a significant role in the follow-up of these patients. This short review aims at summarizing the results of the most relevant published studies with particular interest directed towards a better understanding of the relationship between PSA kinetics and choline PET/CT detection rate and the potential use of PSA kinetics for an optimal selection of patients who may benefit most from this diagnostic procedure particularly at an early stage of biochemical recurrence.     

Influence of PSA,PSA velocity and PSA doubling time on contrast-enhanced <Superscript>18</Superscript>F-choline PET/CT detection rate in patients with rising PSA after radical prostatectomy

Purpose  

To evaluate the accuracy of contrast-enhanced ¹⁸F-choline PET/CT in restaging patients with prostate cancer after radical prostatectomy in relation to PSA, PSA velocity (PSAve) and PSA doubling time (PSAdt).     

Benign fibrous dysplasia on [11C]choline PET: a potential mimicker of disease in patients with biochemical recurrence of prostate cancer

We present the case of a 74-year-old male with biochemical recurrence of prostate cancer who underwent [(11)C]choline PET/CT. The PET/CT demonstrated an intense focus of uptake within the skull base that was initially felt to potentially represent metastatic disease. Subsequent evaluation with MRI and dedicated thin-section CT revealed this area to be benign fibrous dysplasia of the bone. The focal uptake on PET/CT with [(11)C]choline in benign fibrous dysplasia represents a potential mimicker of metastatic disease. Due to recognizing this benign process, our patient was able to avoid systemic treatment and/or focal radiation and was treated with cryotherapy for biopsy-proven local recurrence within the prostate bed. While benign fibrous dysplasia can demonstrate increased radiotracer uptake on other modalities (i.e., bone scintigraphy, FDG PET/CT), its appearance on [(11)C]choline PET/CT has been largely overlooked in the literature. With the increasing use of [(11)C]choline PET/CT for biochemical recurrent prostate cancer evaluation, it is important to understand this potential mimicker of disease.     

Salvage radiotherapy in prostate cancer patients with biochemical relapse after radical prostatectomy

Background

In patients with prostate cancer (PCa) and biochemical progression (BP) after radical prostatectomy (RP), salvage radiotherapy (sRT) improves prostate cancer-specific survival (PCSS), but this evidence is based only on retrospective data.

Patients and methods

In addition to our previous study of 151 patients with PCa and BP after RP, we performed univariate analyses of prostate-specific antigen (PSA) kinetics during sRT. In 11 patients with BP or initiation of hormonal treatment (HT) within 180 days after sRT, risk factors were assessed using Mann–Whitney U tests. PSA doubling times (PSADT) before and after sRT in 82 patients with BP after sRT were compared by a Wilcoxon test.

Results

After a median follow-up of 82 months, analysis of PSA kinetics during sRT did not show a statistically significant impact on a subsequent BP, PCSS, or overall survival at an administered dose of 30 or 45?Gy. The subgroup analysis of patients with early BP or early HT revealed higher Gleason scores (p = 0.008) and preoperative PSA values (p = 0.005), shorter PSADT prior to sRT (p < 0.0005), and longer time intervals from RP until the start of sRT (p = 0.005) compared to all other patients. In patients with subsequent BP, PSADTs were significantly prolonged after sRT (median PSADT 4.5 months before and 9.9 months after sRT, p < 0.0005).

Conclusion

PSA monitoring during sRT did not predict the therapeutic success. Subgroup analysis suggests a lower probability of benefit for patients with the abovenamed risk factors . However, the prolonged PSADT after sRT reflects a benefit of sRT for the vast majority of patients.

     

Evaluation of the PET component of simultaneous [18F]choline PET/MRI in prostate cancer: comparison with [18F]choline PET/CT

Purpose

The aim of this study was to evaluate the positron emission tomography (PET) component of [¹⁸F]choline PET/MRI and compare it with the PET component of [¹⁸F]choline PET/CT in patients with histologically proven prostate cancer and suspected recurrent prostate cancer.

Methods

Thirty-six patients were examined with simultaneous [¹⁸F]choline PET/MRI following combined [¹⁸F]choline PET/CT. Fifty-eight PET-positive lesions in PET/CT and PET/MRI were evaluated by measuring the maximum and mean standardized uptake values (SUV_max and SUV_mean) using volume of interest (VOI) analysis. A scoring system was applied to determine the quality of the PET images of both PET/CT and PET/MRI. Agreement between PET/CT and PET/MRI regarding SUV_max and SUV_mean was tested using Pearson’s product-moment correlation and Bland-Altman analysis.

Results

All PET-positive lesions that were visible on PET/CT were also detectable on PET/MRI. The quality of the PET images was comparable in both groups. Median SUV_max and SUV_mean of all lesions were significantly lower in PET/MRI than in PET/CT (5.2 vs 6.1, p?<?0.05 and 2.0 vs 2.6, p?<?0.001, respectively). Pearson’s product-moment correlation indicated highly significant correlations between SUV_max of PET/CT and PET/MRI (R?=?0.86, p?<?0.001) as well as between SUV_mean of PET/CT and PET/MRI (R?=?0.81, p?<?0.001). Bland-Altman analysis revealed lower and upper limits of agreement of ?2.77 to 3.64 between SUV_max of PET/CT vs PET/MRI and ?1.12 to +2.23 between SUV_mean of PET/CT vs PET/MRI.

Conclusion

PET image quality of PET/MRI was comparable to that of PET/CT. A highly significant correlation between SUV_max and SUV_mean was found. Both SUV_max and SUV_mean were significantly lower in [¹⁸F]choline PET/MRI than in [¹⁸F]choline PET/CT. Differences of SUV_max and SUV_mean might be caused by different techniques of attenuation correction. Furthermore, differences in biodistribution and biokinetics of [¹⁸F]choline between the subsequent examinations and in the respective organ systems have to be taken into account.     

11C]-choline PET/CT in imaging locally advanced prostate cancer

PET Imaging with [11C]-choline has become a useful tool in the investigation of prostate cancer, with as main application the assessment of previously treated patients presenting with rising PSA and negative conventional imaging procedures. In this case report we describe [11C]-choline PET/CT findings in a patient with a locally advanced cancer, which could be successfully identified thanks to the early image acquisition and the delayed urinary excretion of the carbon-11 labeled tracer.     

Salvage radiotherapy in patients with prostate cancer and biochemical relapse after radical prostatectomy

Background and purpose

In patients with prostate cancer (PC) and biochemical relapse after radical prostatectomy, salvage radiotherapy (SRT) could improve PC-specific survival (PCSS) but the timing for initiation is still under discussion. We have demonstrated a low rate of biochemical relapses in a patient series with very low pre-SRT PSA levels after a median follow-up of 42 months. Here, we present an update of that study.

Patients and methods

Overall, 151 patients were analyzed. A biochemical relapse after SRT was diagnosed when the PSA exceeded the post-SRT nadir by 0.2 ng/ml with subsequent increase. Parameters with significant impact on biochemical progression-free survival (BPFS), PCSS, and overall survival (OS) in univariate analysis were included in a multiple Cox regression analysis.

Results

After a median follow-up of 82 months, 18 patients (12?%) had died with 10 (6.6?%) deaths being PC-related. A biochemical progression was diagnosed in 83 patients (55?%). Univariate analysis revealed a significant impact of pre-SRT PSA level, Gleason score, and PSA doubling time (PSADT) on BPFS and for initial tumor stage and Gleason score on OS. Multivariate analysis confirmed the impact of pre-SRT PSA level, Gleason score, and PSADT on BPFS and tumor stage on OS.

Conclusion

In this update, the rate of biochemical relapses increased compared with our previous data. Compared to similar studies, we found a remarkably low rate of PC-related deaths. Our data support early initiation of SRT. However, this treatment strategy, triggered by very low PSA levels, could carry the risk of overtreatment in at least a subset of patients.     

Role of whole-body 18F-choline PET/CT in disease detection in patients with biochemical relapse after radical treatment for prostate cancer

Purpose

The aim of this study was to evaluate the role of whole body ¹⁸F-choline (FCH) positron emission tomography—computed tomography (PET-CT) in detecting and localising disease recurrence in patients presenting biochemical relapse after radical treatment for prostate cancer.

Materials and methods

Fifty-six consecutive patients with increased serum prostate-specific antigen (PSA) levels after radical prostatectomy were included in the study. None of them was receiving hormone treatment at the time of the examination or had been treated during the previous 6 months. All patients underwent whole-body ¹⁸F-choline PET imaging, and the pathological findings were compared with those of further imaging exams, biopsy and follow-up. On the basis of the PSA levels, we divided our patient population into three subgroups: PSA≤1, 15 ng/ml.

Results

Overall, the PET scan detected disease relapse in 42.9% of cases (24/56). PET sensitivity was closely related to serum PSA levels, showing values of 20%, 44% and 81.8% in the PSA≤1, 15ng/ml subgroups, respectively.

Conclusions

In patients with biochemical relapse after radical treatment for prostate cancer, ¹⁸F-choline PET-CT represents a single step, whole-body, noninvasive study that allows disease detection and localisation. The disease detection rate is related to serum PSA levels.