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Integration of 68Ga-PSMA-PET imaging in planning of primary definitive radiotherapy in prostate cancer: a retrospective study

  • Sabrina Dewes1Email author,
  • Kilian Schiller1,
  • Katharina Sauter1,
  • Matthias Eiber1,
  • Tobias Maurer1,
  • Markus Schwaiger1,
  • Jürgen E. Gschwend1,
  • Stephanie E. Combs1 and
  • Gregor Habl1
Radiation Oncology201611:73

https://doi.org/10.1186/s13014-016-0646-2

Received: 11 November 2015

Accepted: 10 May 2016

Published: 26 May 2016

Abstract

Background

Prostate cancer (PC) is one of the most commonly treated cancer entities with radiation therapy (RT). Risk group-adapted treatment and avoidance of unnecessary toxicities relies primarily on accurate tumor staging. Thus, the introduction of prostate-specific membrane antigen (PSMA) in diagnosis and treatment of PC is a highly interesting development in radiation oncology of urologic tumors. The present work is to evaluate the integration of 68Ga-PSMA-PET imaging into standard radiation planning of primary definitive treatment of PC and to determine the impact of PSMA imaging on tumor staging.

Methods

The data of 15 patients treated for PC between August 2013 and April 2015 were evaluated. Treatment planning included 68Ga-PSMA-PET imaging. We analyzed whether the use of PSMA-imaging led to a change of the TNM stage and if it influenced the RT treatment approach or the target volume, due to changes in the gross tumor volume (GTV) or clinical target volume (CTV), in the final treatment plan.

Results

In 53.3 % of the analyzed patients a change occurred in the TNM stage based on 68Ga-PSMA-PET examination. The RT concept changed in 33.3 % of all patients, leading to relevant changes in the planning target volume. Among these, an additional irradiation of the pelvic lymph drainage due to tracer uptake in lymph nodes was performed in 25 %. Furthermore, boost volumes of PET-positive lymph nodes were added in 80 % of these cases. A down staging due to the 68Ga-PSMA-PET examination occurred in 13.3 % of all cases.

Conclusions

The integration of 68Ga-PSMA-PET-imaging into the RT treatment planning process can be useful for detailed target volume planning. The performance of a 68Ga-PSMA-PET frequently leads to changes in the TNM stage, altering the RT treatment regimen and the target volume. A prospective trial is underway to evaluate the impact of 68Ga-PSMA-PET based treatment planning on outcome.

Keywords

PSMA-PETProstate cancerRadiation therapyRadiation oncologyTreatment planning

Background

Prostate cancer (PC) is the most common tumor entity in males in many developed countries [1]. Almost 65.000 patients were newly diagnosed with PC in Germany alone in 2011 and every year over 10.000 die from it [2]. There are several treatment options for localized PC, among them radiation therapy (RT), which may be administered alone or in combination with hormonal therapy [3]. Definitive RT for PC relies primarily on accurate clinical and radiological tumor staging. To differentiate between local, regional, or systemic disease, initial staging provides the basis for further treatment decisions and enables risk group-adapted treatment. On the one hand staging is of paramount importance to increase the curative chance of patients and on the other to spare them from unnecessary toxicities. Several imaging modalities are used for staging PC such as CT, MRI or bone scintigraphy. Nuclear medicine methods include radioactive marked tracers such as Choline-PET imaging, each limited by a low specificity. PSMA-PET-imaging has been shown to be more sensitive as well as specific for PC staging [46].

Prostate-specific membrane antigen (PSMA) is a cell surface protein with high expression in PC cells [7]. At lower levels it is expressed within various organs such as salivary gland tissues and kidneys, and less so in liver, spleen, bowel and healthy prostate structures [810]. On the surface of PC cells it has been shown to be a thousand-fold increased compared to the other mentioned tissues [7]. In 2012, 68Ga-PSMA was developed as a novel PSMA-ligand and very recent studies show promising results for its usefulness in recurrent prostate cancer or as a staging tool [5, 9, 11]. Its introduction in diagnosis as well as treatment of PC is one of the most interesting developments in radiation oncology of urologic tumors.

However, the implementation of 68Ga-PSMA-PET-imaging in clinical routine is still only available in a few centers worldwide. Few data is available, especially on the value for staging and the impact on stage adaption during treatment planning for RT. The present work is to evaluate the integration of 68Ga-PSMA-PET-imaging into standard radiation planning of a primary definitive treatment of PC and to determine the influence on staging and on changes in the initially planned treatment concept for definitive RT in PC.

Methods

Between August 2013 and April 2015, 15 patients were planned for definitive RT of the prostate with treatment planning based on CT, MRI and 68Ga-PSMA-PET-imaging at our institution. All patients gave written informed consent for the purpose of anonymized evaluation and publication of their data. All reported investigations were conducted in accordance with the Helsinki Declaration and with national regulations. The retrospective analysis was approved by the Ethics Committee of the Technical University Munich (permit 5665/13).

68Ga-PSMA-PET-imaging was regularly CT based. In one case (patient #3) MRI was selected because of better comparability with preceding images. Pre-treatment 68Ga-PSMA-PET CT or MRI was performed between June 2013 and October 2014 in the staging process. Patient characteristics are shown in Table 1. The procedure of elaboration and application of the 68Ga-PSMA-ligand complex has been described previously [1214].
Table 1

Patients´ characteristics

Median Age (years, range)

74 (59–82)

Gleason Score n (%)

 

Low risk (≤6)

5 (33.3)

Intermediate risk (7)

4 (26.7)

High risk (>7)

6 (40.0)

Serum PSA (ng/ml) n (%)

 

Low risk (≤10)

7 (46.7)

Intermediate risk (10–20)

3 (20.0)

High risk (>20)

5 (33.3)

Initial tumor stage (clinical examination and CT/MRI), n (%)

 

Biopsy T1c

7 (46.7)

Intermediate risk (T2b)

1 (6.7)

High risk (≥T2c)

7 (46.7)

Gleason score, PSA levels and Tumor stage risk group assignment according to the 2014 National Comprehensive Cancer Network guidelines on prostate cancer 

All cases were discussed in an interdisciplinary panel of experienced radiation oncologists, radiologists, nuclear medicine physicians and urologists and treatment decisions were taken on consensus. Based on histo-pathological Gleason scores, pre-treatment PSA levels and clinical staging patients were assigned to risk groups (low, intermediate and high risk) according to the 2014 National Comprehensive Cancer Network guidelines on prostate cancer [15].

Retrospectively initial pre-68Ga-PSMA-PET tumor stages were classified according to the 2010 version AJCC/UICC staging system - including Gleason score, initial PSA levels, TNM stage, as well as a calculation of the Roach formula (risk of lymph node involvement [%] = 2/3 (PSA) + (GS-6) × 10) [16]. According to internal standard operation procedures of our department and following international guidelines, initial treatment decisions were made without the information obtained by 68Ga-PSMA-PET imaging based on CT/MRI as well as histo-pathological information available including PSA-level [3, 17]. After PSMA-imaging, all information was reviewed and re-classification was performed with the additional information taken into account. We evaluated the number of cases in which the information obtained by 68Ga-PSMA-PET imaging led to a change in staging and subsequently resulted in a change of the RT concept, such as additional irradiation of the lymph node regions or local dose escalations.

For treatment planning, CT scans with 3 mm slice thickness at full bladder and empty rectum were performed. For all patients presenting tumor stages cT1-cT3a the CTV definition included the prostate and the base of the seminal vesicles. For patients in stadium cT3b the seminal vesicles were included completely in the CTV. To obtain the PTV of the prostate 7 mm were added to the CTV in all directions. Patients with actual lymph node involvement (cN+) or an increased risk of an involvement (risk more than 20 % according to the Roach formula) received an irradiation of the pelvic lymph nodes. We defined the corresponding PTV of the lymph nodes, including the obturatory, internal and external iliac, common iliac and presacral (down to S3) lymph nodes, with a 5 mm margin [18]. If patients showed an increased uptake in 68Ga-PSMA-PET in defined lymph nodes, a simultaneously integrated boost was performed to the enhancement. The PTV of the suspected lymph node included the morphological correlate of the enhanced lymph node increased by at least 5 mm.

All patients received an intensity-modulated radiotherapy (IMRT): eight patients were treated with Tomotherapy® (Accuray, USA) and seven patients received an IMRT in RapidArc® technique by Varian, USA. The treatment was performed with full bladder and empty rectum under daily image guidance (IGRT).

Results

A total of 15 patients were included into the present analyses. Data on imaging and on treatment decisions was followed prospectively through collaboration between the Departments of Nuclear Medicine, Urology and Radiation Oncology. Table 2 illustrates all tumor stages of enrolled patients; initial as well as after 68Ga-PSMA imaging. In 8 out of 15 patients (53.3 %) of all analyzed patients a change occurred in the TNM stadium due to the performed 68Ga-PSMA-PET examination. In 13 out of 15 patients (86.7 %) anti-hormonal treatment was given either before RT (80 %) or concurrently (6.7 %).
Table 2

Detailed information on each patient

Patient

Gleason score

PSA (ng/ml)

Roach formula risk (%)

Primary staging (CT = 1, MRI = 2, Choline-PET = 3)

cTNM without PSMA-PET

cTNM including PSMA-PET

     

T

N

M

T

N

M

1

6

19.1

13

1, 2, 3

1c

1

0

1c

0

0

2

7

8.5

16

1,2

3a

0

0

3b

0

0

3

8

9.6

26

1,2

2c

X

0

2c

1

0

4

6

39.6

26

1,2

3b

0

0

3b

1

0

5

9

34.2

53

1

1c

0

0

2b

0

0

6

6

8.2

6

1,2

2c

0

0

2c

0

0

7

7

36

34

1,2

3a

0

0

3a

1

1 a

8

6

10.8

7

1

1c

0

0

2a

0

0

9

7

23

25

1,2

3b

0

0

3b

0

0

10

8

9.4

26

1,2,3

2c

1

0

2c

0

0

11

8

13.5

29

1

2b

0

0

3b

0

0

12

7

8.7

16

1,2

1c

0

0

2a

0

0

13

6

63.9

43

1

1c

0

0

2c

0

0

14

9

9.6

36

1,2

1c

0

0

2c

0

0

15

8

23

35

1, 2

1c

X

X

2c

1

Xb

Shown are biopsy Gleason score, maximum PSA level before treatment and calculation of lymph node involvement following the Roach formula, as well as evolvement of tumor stages before and after PSMA-PET imaging (changes are in bold). aM1 based on para-aortal lymph nodes. bPSMA uptake in the 5th rib right, without CT morphologic correlation, suggesting possible bone metastasis

Down-staging

Down-staging occurred in 2 cases (13.3 %). Those two cases were the only ones to receive a previous 11C-Choline-PET-CT. Radiologically positive lymph nodes were described on 11C-Choline-PET-CT, but did not show enhancement in the 68Ga-PSMA-PET scan and were therefore judged as not suspicious. In one patient (#1, Fig. 1a, b) multiple paraaortal and iliacal lymph nodes showed a strong uptake and morphological correlates in the previous Choline-PET-CT examination. In the 68Ga-PSMA-PET-CT, which was performed for clarification purposes, none of the nodes showed tracer accumulation. Thus, it was assumed that the disease was locally limited and the RT volume delineation included only the prostate. In another patient (#10), one particularly suspicious preacetabular located lymph node was identified among a few others that showed enhancement in a Choline-PET-CT. In the following 68Ga-PSMA-PET-CT imaging, no evidence at all was seen for lymph node involvement.
Fig. 1

Down-staging by 68Ga-PSMA-PET. Choline-PET-CT (a) with elevated tracer uptake of left iliac lymph node. 68Ga-PSMA-PET (b) does not confirm the questionable involvement seen by Choline-PET-CT

Up-staging

Up-staging was seen in 6 patients (40 %). In 2 cases the T stadium had to be corrected, and in another 4 patients a strong tracer uptake in initially unsuspicious lymph nodes was seen. To illustrate this, we shall highlight two cases. In the first case, Patient #2 had a primary tumor which was detected by MRI, but also showed a questionable extra capsular spread. The radiology colleagues described it as rather atypical for the tumor. Later a 68Ga-PSMA-PET-CT examination confirmed the extra capsular tumor spread on the dorsal right side with additional infiltration of the seminal vesicles. In this case the T stage evolved from cT3a to a cT3b (Fig. 2a, b).
Fig. 2

Up-staging due to extra capsular spread by 68Ga-PSMA-PET. Questionable extra capsular spread on MRI (a). In 68Ga-PSMA-PET imaging (b) is strong tracer uptake in the bladder and dorsal, as indicated by the arrow, in the extra capsular region, suggesting a strong possibility of its involvement

In the second case, neither MRI nor CT found any indication of lymph node metastases in patient #4, but after 68Ga-PSMA-PET-CT examination of one pararectal left lymph node, another presacral right (Fig. 3a, b), and several others along the iliacal vessels, a pronounced tracer uptake was shown. Without the positive lymph nodes seen in the PET examination, the pelvic lymphatic drainage would have been irradiated due to the risk of lymph node involvement of 26 % according to the Roach formula. Including the newly obtained information the affected lymph nodes were treated with a higher radiation dose (54 à 2.17 Gy as a simultaneously integrated boost) than the surrounding pelvic lymphatics (45 à 1.8 Gy). The treatment plan is illustrated in Fig. 4a. The primary tumor within the prostate received no higher dose and the whole prostate plus seminal vesicles were treated to a total dose of 74 Gy.
Fig. 3

Up-staging due to lymph node involvement by 68Ga-PSMA-PET. Non-suspicious lymph nodes on MRI (a) presacral. In 68Ga-PSMA-PET imaging (b), the lymph node displays enhancement and was thus treated with a higher radiation dose

Fig. 4

Treatment plan comparison. Basic treatment plan (a), including lymph node irradiation up to 45 Gy à 1.8 Gy. Based on the information obtained by 68Ga-PSMA-PET imaging, PET-positive nodes receive a simultaneous integrated boost to 54 Gy à 2.17 Gy. In comparison with Fig. 4a an example of the dose distribution (b) without the knowledge through the 68Ga-PSMA-PET; the lymph node involvement would not have been suspected and therefore only the prostate itself would have been treated

No change of stage

Seven patients (46.7 %) experienced no change of stage. This also included those cases where the biopsy confirmation (T1c) evolved to any other T-stage based on image modalities.

As shown in Table 3, advanced tumors with initially higher T-stages have an increased risk of upstaging by 68Ga-PSMA imaging. On the other hand small tumors (lower T-stages) were more likely to experience down-staging through 68Ga-PSMA-PET.
Table 3

Distribution of prostate cancer T stage before and after PSMA-PET imaging of the prostate

T stage

Initial clinical Staging: n (%)

Relative up-staging by PSMA-PET-imaging: n (%)

Relative down-staging by PSMA-PET-imaging: n (%)

PSMA-PET-imaging staging: n (%)

Biopsy T1c

6 (40.0)

1 (6.7)

1 (6.7)

0

Low risk (≤T2a)

0

0

0

2 (13.3)

Intermediate risk (T2b)

2 (13.3)

1 (6.7)

0

1 (6.7)

High risk (≥T2c)

7 (46.7)

4 (26.7)

1 (6.7)

12 (80.0)

Similarly, the Gleason score seemed to influence the likelihood of a tumor up-staging. With a Gleason score of 7 or under, only 1 patient (6.7 %) experienced a further up-staging. For scores of 7 or over, 2 (13.3 %) and respectively 3 (20 %) cases had to be grouped into a higher TNM stadium. Down-staging worked up for Gleason score was balanced for patients with scores over and lower than 7. Concerning PSA levels the trend seemed to be less convincing. The six up-stagings were spread out over three groups. 3 cases were found for PSA levels under 10 ng/ml and one case for PSA levels between 10 and 20 ng/ml. 2 cases occurred in patients having initial PSA levels over 20 ng/ml. Nevertheless, down-staging was seen in 2 patients with PSA levels under 20 ng/ml, as seen in Table 4.
Table 4

Dependence on Gleason Score and PSA serum levels for up- and down-staging

 

Number

Tumor up-staging: n (%)

Tumor down-staging: n (%)

Gleason score <7

5

1 (6.7)

1 (6.7)

Gleason score 7

4

2 (13.3)

0

Gleason score > 7

6

3 (20.0)

1 (6.7)

PSA level <10 ng/ml

7

3 (20.0)

1 (6.7)

PSA level 10–20 ng/ml

3

1 (6.7)

1 (6.7)

PSA level >20 ng/ml

5

2 (13.3)

0

The radiotherapy concept was changed in 33.3 % of the patients analyzed. This produced relevant changes in the gross tumor volume and clinical target volume. Among these changes an additional irradiation of the pelvic lymph drainage due to tracer uptake in lymph nodes was performed in 25 %. Furthermore, boost volumes on positive lymph nodes detected by 68Ga-PSMA-PET were added in 80 % of these cases (Fig. 4a and b).

Discussion

68Ga-PSMA-PET has shown high diagnostic accuracy for patients with PC. The data from the present manuscript show that 68Ga-PSMA-PET imaging had a huge impact on staging. Thus, compared to standard imaging based on pathological parameters, PSA values and imaging with CT and/or MRI only, a substantial impact on tumor staging and re-staging can be expected based on 68Ga-PSMA-PET imaging. Since in definitive RT for PC precise delineation of involved tissue as well as tissue at risk is necessary, and since there is a clear benefit of dose escalations to involved tissue, the diagnostic value of 68Ga-PSMA PET is evident.

Recently, the usefulness and accuracy of 68Ga-PSMA-PET imaging has been described increasingly in the recurrent setting of PC [5, 11, 19, 20]. For example, Eiber et al. [5] attested significantly higher detection rates of PC and lymph nodes as previously reported for other imaging modalities. This particularly applied in the range of low PSA-levels (<0.5 ng/mL). In 33 % of cases, the tumor site was exclusively detected by 68Ga-PSMA-PET examination. An additional 25 % of the patients showed lesions that were not detectable by CT. In total, over 50 % of crucial information was identified by 68Ga-PSMA-PET for final diagnosis, as well as staging and treatment decisions. The specificity of 68Ga-PSMA-PET has been demonstrated by the use of PSMA-radioguided surgery as well as for lymph node staging in primary PC [21, 22]. With the radiotherapy concept changing in a third of all patients we assume that a better sensitivity and specificity may lead to improved radiotherapy concepts in patients having received a 68Ga-PSMA-PET.

All 68Ga-PSMA PET examinations were performed for treatment planning on the premises of 68Ga-PSMA-PET imaging as a “gold standard”. For precise diagnosis, correlation with pathological analyzes is necessary. This is currently being done for the diagnostic value of lymph node identification within a prospective trial at our institution. Though more data is still needed to verify sensitivity and specificity of the 68Ga-PSMA-PET, promising studies have been conducted. A current study by Maurer et al. [23] showed for primary patients before radical prostatectomy and patients who underwent surgery for lymph node metastases a high histo-pathologically proven sensitivity (75 and 65.9 %) and specificity (98.8 and 98.9 %). CT or MRI imaging sensitivity (41.7 and 43.9 %) and specificity (85.5 and 85.4 %) was clearly lower. Another recent study by Giesel et al. confirms these findings [24].

It should also be mentioned that PSMA-negative PC seems to be rare, but false negative cases have been reported in the literature [8, 20, 25]. Whether this approach is correct will be verified by long-term PSA-levels. At our institution PSA-levels are monitored every 3 months after radiation therapy.

Nevertheless, in previous studies other imaging modalities such as CT and MRI showed similar performances in PC nodal staging by indirectly assessing nodal invasion measuring lymph node diameter. Consequently, their sensitivity was proven to be low. Using a 10 mm threshold, the sensitivity was reported to be less than 40 % [26]. Functional PET imaging, mostly using radiolabeled-choline derivatives, are of limited value and often underestimate the extent of metastatic spread [27]. Evangelista et al. [28] evaluated, in a big meta-analysis, a high specificity for 11C-Choline-PET CT of 95 % in primary lymph node staging but a low sensitivity of just 50 %. Husarik et al. [29] found a sensitivity to detect recurrent disease of 86 % and described these results as rather discouraging, especially in terms of its inability to detect small metastases - recurrent disease was reliably diagnosed in patients with PSA levels of >2 ng/ml. In another study Choline-PET-CT was found to be statistically significantly inferior when compared to 68Ga-PSMA-PET-CT in a recurrent setting as described by Afshar-Oromieh et al. [24].

Interestingly, there have been studies that support the theory that detection rates increase parallel with elevated PSA levels [30]. In a primary setting a tailored treatment approach is very important, and with mostly considerably elevated PSA levels, 68Ga-PSMA-PET imaging could prove to be overly effective. Here, the measurement of PSA level alone can at best calculate the risk of lymph node metastases by using the Roach formula [16]. On a similar note, it has been noted that there is higher expression in lesions with higher Gleason scores [5, 31]. The Gleason score as well as PSA levels were also taken into account in our study.

One main limitation of this analysis is its small patient number. However, since no data are currently available and 68Ga-PSMA-PET imaging is performed at several centers, the results provide a useful basis for decision-making in radiation oncology. Additionally, the homogenous results in the present “typical“ PC patient population underline the reliability of the reported data. It is important to note that in patients with higher T-stages, as well as higher PSA-values, the impact of 68Ga-PSMA-PET is larger on restating than in other tumor stages, meaning that in those patients a larger amount of up-stagings were observed than for lower tumor stages.

However, other factors such as anti-hormonal treatment might influence staging changes and therefore represent limitations to our study. In both of the down-staging cases anti-hormonal treatment was given either at the time or before 68Ga-PSMA imaging. These factors possibly had an effect on PSMA-image enhancement and subsequent down-staging. In contrast, Afshar-Oromieh et al. [11] showed that patients taking anti-hormonal medication at the time of the 68Ga-PSMA-PET examination had more often positive PET results than patients not receiving hormonal therapy. Also, in some cases the time span between initial imaging modalities and 68Ga-PSMA-PET was up to a few months (maximum of 3 months - e.g. due to bridging anti-hormonal treatment). Therefore the possibility cannot be excluded that tumor stages in a few cases not only evolved because of the diagnostic tool, but also simply because of time.

In summary, we see great potential for 68Ga-PSMA-PET imaging. On one hand, in the case of down-staging, patients are potentially spared from unnecessary toxicities to surrounding tissues due to smaller radiation fields. For example, radiation doses could be drastically reduced by only treating lymphatic drainage if pelvic enhancements are obtained by 68Ga-PSMA-PET and not based on the calculated lymph node risk according to the Roach formula. In order to standardize this procedure at least PSA-long-term observations have to be conducted. On the other hand, in the case of up-staging, enlarged radiation volumes were its consequence and additional radiation dose (boost) to affected lymph nodes or within the prostate region could potentially translate into improved local control and/or overall survival for our patients. This will be evaluated within a prospective clinical trial at our institution.

Conclusions

The integration of 68Ga-PSMA-PET imaging into RT treatment planning can be a powerful tool and useful method for detailed target volume delineation. In addition to the indication for PSA persistence after radical prostatectomy or PSA relapse without image morphological correlate, a 68Ga-PSMA-PET can also be advantageous for radiation treatment planning in primary PC. Assuming 68Ga-PSMA-PET as “gold standard” we showed in this initial patient series that the implementation of 68Ga-PSMA -PET hybrid imaging frequently led to changes in the TNM staging and consequently influences the radiotherapeutic treatment regimen as well as the clinical target volumes. This yields the possibility for boost volumes directed to PET-positive areas. Whether this will be reflected by an improvement in survival rates needs to be investigated in larger prospective studies.

Notes

Declarations

Acknowledgements

The development of 68Ga-PSMA-PET synthesis was supported by SFB 824 (DFG Sonderforschungsbereich 824, project Z1) from the Deutsche Forschungsgemeinschaft, Bonn, Germany.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Technische Universität München (TUM), Klinik und Poliklinik für RadioOnkologie und Strahlentherapie

References

  1. World Health Organization. Cancer mortality and morbidity. 2008.Google Scholar
  2. Robert Koch Institut Bundesamt. Prostataerkrankungen - Heft 36. Gesundheitsberichterstattung des Bundes. Januar 2007Google Scholar
  3. Leitlinie Onkologie. Interdisziplinäre Leitlinie der Qualität S3 zur Früherkennung, Diagnose und Therapie der verschiedenen Stadien des Prostatakarzinoms. 2. Aktualisierung - Oktober 2014; Version 2.0 – 2. Aktualisierung - Oktober 2014 (AWMF-Register-Nummer (034-022OL)).Google Scholar
  4. Bundschuh RA, Wendl CM, Weirich G, Eiber M, Souvatzoglou M, Treiber U, Kubler H, Maurer T, Gschwend JE, Geinitz H, Grosu AL, Ziegler SI, Krause BJ. Tumour volume delineation in prostate cancer assessed by [11C]choline PET/CT: validation with surgical specimens. Eur J Nucl Med Mol Imaging. 2013;40(6):824–31. doi:10.1007/s00259-013-2345-7. Epub 2013/02/08.View ArticlePubMedGoogle Scholar
  5. Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B, Kubler H, Haberkorn U, Eisenhut M, Wester HJ, Gschwend JE, Schwaiger M. Evaluation of hybrid 68Ga-PSMA-ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med. 2015;56(5):668–74. doi: 10.2967/jnumed.115.154153. Epub 2015 Mar 19.View ArticlePubMedGoogle Scholar
  6. Maurer T, Beer AJ, Wester HJ, Kubler H, Schwaiger M, Eiber M. Positron emission tomography/magnetic resonance imaging with 68Gallium-labeled ligand of prostate-specific membrane antigen: promising novel option in prostate cancer imaging? Int J Urol. 2014;21(12):1286–8. doi:10.1111/iju.12577. Epub 2014/07/23.View ArticlePubMedGoogle Scholar
  7. Ghosh A, Heston WD. Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. J Cell Biochem. 2004;91(3):528–39.View ArticlePubMedGoogle Scholar
  8. Mannweiler S, Amersdorfer P, Trajanoski S, Terrett J, King D, Mehes G. Heterogeneity of prostate-specific membrane antigen (PSMA) expression in prostate carcinoma with distant metastasis. Pathol Oncol Res. 2009;15(2):167–72. doi: 10.1007/s12253-008-9104-2. Epub 2008 Sep 18.View ArticlePubMedGoogle Scholar
  9. Afshar-Oromieh A, Malcher A, Eder M, Eisenhut M, Linhart H, Hadaschik B, Holland-Letz T, Giesel F, Kratochwil C, Haufe S, Haberkorn U, Zechmann CM. PET imaging with a [68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions. Eur J Nucl Med Mol Imaging. 2013;40(4):486–95. doi: 10.1007/s00259-012-2298-2. Epub 2012 Nov 24.View ArticlePubMedGoogle Scholar
  10. Silver DA, Fair WR, Heston WD, Cordon-Cardo C. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res. 1997;3(1):81–5.PubMedGoogle Scholar
  11. Afshar-Oromieh A, Avtzi E, Giesel F, Holland-Letz T, Linhart H, Eder M, Eisenhut M, Boxler S, Hadaschik B, Kratochwil K, Weichert W, Kopka K, Debus J, Haberkorn U. The diagnostic value of PET/CT imaging with the (68)Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2015;42(2):197–209. doi: 10.1007/s00259-014-2949-6. Epub 2014 Nov 20.Google Scholar
  12. Eder M, Neels O, Muller M, Bauder-Wust U, Remde Y, Schafer M, Hennrich U, Eisenhut M, Afshar-Oromieh A, Haberkorn U, Kopka K. Novel Preclinical and Radiopharmaceutical Aspects of [68Ga]Ga-PSMA-HBED-CC: A New PET Tracer for Imaging of Prostate Cancer. Pharmaceuticals (Basel). 2014;7(7):779–96. doi: 10.3390/ph7070779.View ArticleGoogle Scholar
  13. Martin R, Juttler S, Muller M, Wester HJ. Cationic eluate pretreatment for automated synthesis of [(6)(8)Ga]CPCR4.2. Nucl Med Biol. 2014;41(1):84-9. doi: 10.1016/j.nucmedbio.2013.09.002. Epub 2013 Oct 9.View ArticlePubMedGoogle Scholar
  14. Schafer M, Bauder-Wust U, Leotta K, Zoller F, Mier W, Haberkorn U, Eisenhut M, Eder M. A dimerized urea-based inhibitor of the prostate-specific membrane antigen for 68Ga-PET imaging of prostate cancer. EJNMMI Res. 2012;2(1):23. doi: 10.1186/2191-219X-2-23.View ArticlePubMedPubMed CentralGoogle Scholar
  15. National Comprehensive Cancer Network. Guidelines on prostate cancer: National Comprehensive Cancer Network; 2014Google Scholar
  16. Roach 3rd M, Marquez C, Yuo HS, Narayan P, Coleman L, Nseyo UO, Navvab Z, Carroll PR. Predicting the risk of lymph node involvement using the pre-treatment prostate specific antigen and Gleason score in men with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys. 1994;28(1):33–7. Epub 1994/01/01.View ArticlePubMedGoogle Scholar
  17. AJCC/UICC. AJCC Cancer Staging Manual. New York: Springer; 2010. p. 457.Google Scholar
  18. Lawton CA, Michalski J, El-Naqa I, Buyyounouski MK, Lee WR, Menard C, O'Meara E, Rosenthal SA, Ritter M, Seider M. RTOG GU Radiation oncology specialists reach consensus on pelvic lymph node volumes for high-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2009;74(2):383–7. doi:10.1016/j.ijrobp.2008.08.002.PubMedPMID:18947938;PubMedCentralPMCID:PMCPMC2905150.View ArticlePubMedPubMed CentralGoogle Scholar
  19. Maurer T GJ, Wester HJ, Souvatzoglou M, Beer AJ, Holzapfel K, Wierich G, Haller B, Kübler H, Schwaiger M, Eiber M. PET imaging with prostate-specific membrane antigen (PSMA) for staging of primary prostate cancer with 68Ga-HBED-PSMA. ASCO 20152015.Google Scholar
  20. Afshar-Oromieh A, Zechmann C, Malcher A, Eder M, Eisenhut M, Linhart H, Holland-Letz T, Hadaschik B, Giesel F, Debus J, Haberkorn U. Comparison of PET imaging with a (68)Ga-labelled PSMA ligand and (18)F-choline-based PET/CT for the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2014;41(1):11–20. doi: 10.1007/s00259-013-2525-5. Epub 2013 Sep 27.View ArticlePubMedPubMed CentralGoogle Scholar
  21. Maurer T, Weirich G, Schottelius M, Weineisen M, Frisch B, Okur A, Kubler H, Thalgott M, Navab N, Schwaiger M, Wester HJ, Gschwend JE, Eiber M. Prostate-specific Membrane Antigen-radioguided Surgery for Metastatic Lymph Nodes in Prostate Cancer. Eur Urol. 2015;68(3):530–4. doi: 10.1016/j.eururo.2015.04.034.View ArticlePubMedGoogle Scholar
  22. Budäus L, Leyh-Bannurah SR, Salomon G, Michl U, Heinzer H, Huland H, Graefen M, Steuber T, Rosenbaum C. Initial Experience of (68)Ga-PSMA PET/CT Imaging in High-risk Prostate Cancer Patients Prior to Radical Prostatectomy. Eur Urol. 2016;69(3):393–6. doi: 10.1016/j.eururo.2015.06.010.View ArticlePubMedGoogle Scholar
  23. Maurer T, Gschwend JE, Rauscher I, Souvatzoglou M, Haller B, Weirich G, Wester HJ, Heck M, Kuebler H, Beer AJ, Schwaiger M, Eiber M. Diagnostic Efficacy of 68-Gallium-PSMA Positron Emission Tomography compared to conventional imaging in lymph node staging of 130 consecutive patients with intermediate to high risk prostate cancer. J Urol. 2016;195(5):1436–43. doi: 10.1016/j.juro.2015.12.025. Epub 2015 Dec 9.View ArticlePubMedGoogle Scholar
  24. Giesel FL, Fiedler H, Stefanova M, Sterzing F, Rius M, Kopka K et al. PSMA PET/CT with Glu-urea-Lys-(Ahx)-(68Ga(HBED-CC)) versus 3D CT volumetric lymph node assessment in recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2015;42(12):1794–800. doi: 10.1007/s00259-015-3106-6.View ArticlePubMedPubMed CentralGoogle Scholar
  25. Bostwick DG, Pacelli A, Blute M, Roche P, Murphy GP. Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 184 cases. Cancer. 1998;82(11):2256–61.View ArticlePubMedGoogle Scholar
  26. Hovels AM, Heesakkers R, Adang EM, Jager GJ, Strum S, Hoogeveen YL, Severens JL, Barentsz JO. The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with prostate cancer: a meta-analysis. Clin Radiol. 2008;63(4):387–95. doi: 10.1016/j.crad.2007.05.022. Epub 2008 Feb 4.View ArticlePubMedGoogle Scholar
  27. Umbehr MH, Muntener M, Hany T, Sulser T, Bachmann LM. The role of 11C-choline and 18 F-fluorocholine positron emission tomography (PET) and PET/CT in prostate cancer: a systematic review and meta-analysis. Eur Urol. 2013;64(1):106-17. doi: 10.1016/j.eururo.2013.04.019. Epub 2013 Apr 19.View ArticlePubMedGoogle Scholar
  28. Evangelista L, Guttilla A, Zattoni F, Muzzio PC, Zattoni F. Utility of choline positron emission tomography/computed tomography for lymph node involvement identification in intermediate- to high-risk prostate cancer: a systematic literature review and meta-analysis. Eur Urol. 2013;63(6):1040–8. doi:10.1016/j.eururo.2012.09.039. Epub 2012/10/06.View ArticlePubMedGoogle Scholar
  29. Husarik DB, Miralbell R, Dubs M, John H, Giger O, Gelet A, Cservenyak T, Hany TF. Evaluation of [(18)F]-choline PET/CT for staging and restaging of prostate cancer. Eur J Nucl Med Mol Imaging. 2008;35(2):253–63. Epub 2007 Oct 10.View ArticlePubMedGoogle Scholar
  30. Beer AJ, Eiber M, Souvatzoglou M, Schwaiger M, Krause BJ. Radionuclide and hybrid imaging of recurrent prostate cancer. Lancet Oncol. 2011;12(2):181–91. doi: 10.1016/S1470-2045(10)70103-0. Epub 2010 Jul 6.View ArticlePubMedGoogle Scholar
  31. Ross JS, Sheehan C, Fisher H, Kaufman RJ, Kaur P, Gray K, Webb I, Gray G, Mosher R, Kallakury BV. Correlation of primary tumor prostate-specific membrane antigen expression with disease recurrence in prostate cancer. Clin Cancer Res. 2003;9(17):6357–62.PubMedGoogle Scholar

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