Prostate Cancer and Prostatic Diseases (2007) 10, 307–310 & 2007 Nature Publishing Group All rights reserved 1365-7852/07 $30.00 www.nature.com/pcan
CASE REPORT
Incidental diagnosis of a PSA-negative prostate cancer by 18 FDG PET/CT in a patient with hypopharyngeal cancer J Bucerius1, H Ahmadzadehfar1, N Hortling2,3, AY Joe1, H Palmedo1 and H-J Biersack1 1
Department of Nuclear Medicine, University of Bonn, Bonn, Germany; 2Department of Radiology, University of Bonn, Bonn, Germany and 3Gemeinschaftspraxis fu¨r Radiologie und Nuklearmedizin, Siegburg, Germany
Diagnosis of prostate cancer (PC) still remains critical as non-invasive screening with prostate specific-antigen (PSA) lacks to indicate malignancy of the prostate in some cases. Recent research has shown that clinically meaningful PC can develop in patients with a PSA value o4 ng/ml, frequently defined as upper limit of normal serum PSA levels. Furthermore, both morphological (computed tomography (CT), magnetic resonance imaging, transrectal ultrasound) and functional imaging with 18fluorodeoxyglucose positron emission tomography (FDG-PET) are associated with several limitations for primary diagnosis of PC. We report a case of an incidentally diagnosed PSAnegative PC by 18FDG PET/CT in a patient with a previous diagnosis of a hypopharyngeal cancer. Prostate Cancer and Prostatic Diseases (2007) 10, 307–310; doi:10.1038/sj.pcan.4500959; published online 13 March 2007
Keywords: PSA;
18
FDG-PET/CT; prostate cancer
Introduction The incidence of prostate cancer (PC) is rising in the industrialized countries with a tendency towards an earlier onset, making PC one of the most common cancers causing death from malignancy.1 Unfortunately, diagnosis of PC still remains critical as, despite its widespread use, testing with prostate-specific antigen (PSA) still is imprecise, although it is associated with acceptable sensitivities and specificities. This is mainly owing to the fact that alterations in serum PSA levels do not always correspond to the underlying disease of the prostate and/or its clinical outcome.2 Furthermore, recent research has shown that clinically significant PC can also develop in patients with a PSA value o4ng/ml, frequently defined as upper limit of normal serum PSA levels. Consequently, ‘watchful waiting’ approaches have been suggested not to be appropriate for young patients or those with a life expectancy of greater than 15 years.3,4 As such, additional non-invasive diagnostic measures selecting patients who are candidates for further invasive diagnostic procedures, such as prostate biopsy are required. However, despite technical progress and the availability of state-of-the-art methods such as computed tomography (CT), magnetic resonance imaging (MRI), transrectal ultrasound and fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET), the visualization of primary PC, its relapse Correspondence: Dr J Bucerius, Department of Nuclear Medicine, University of Bonn, Sigmund-Freud-Str. 25, Bonn 53105, Germany. E-mail:
[email protected] Received 10 August 2006; revised 12 January 2007; accepted 17 January 2007; published online 13 March 2007
and its lymph node metastases is still a clinically relevant problem as the diagnostic results remain unsatisfactory. MRI and CT are often unable to accurately stage the extent of prostatic malignancies.5–8 On the other hand, the use of FDG-PET, introduced as a promising alternative, has become one of the most important and innovative clinical applications in oncology.9 Even with persisting high costs, FDG-PET is almost routinely used in the clinical management of certain cancer patients. Additionally, FDG-PET has become an efficient modality for whole-body scanning in a reasonably short time.9,10 However, FDG-PET has an unsatisfactory diagnostic value in PC, because the tumor grows relatively slowly in most cases and shows a lower or even absent FDG uptake compared to other cancers.11,12 Furthermore, the local assessment of PC is sometimes difficult as FDG is excreted in the urine and accumulates in the bladder and prostatic urethra, which effectively masks any uptake in the prostatic Consequently, several previously parenchyma.11 published studies failed to show a beneficial impact of FDG-PET, except in the detection and localization of distant metastases in hormone-refractory PC.2,5,6,9,12–15 Additionally, even the recently introduced PET/CT technique, adding morphological information to metabolic data of FDG-PET, failed to improve the diagnostic value of FDG-PET imaging for PC in a small series of patients.15 Data regarding new radiotracers for the diagnosis of PC, for example 11C-choline, seem to have a beneficial impact on the diagnostic value as compared to FDG-PET, but data are still discussed controversially and, as of yet, failed to show a significant correlation between the uptake of 11C-choline and tumor grade or Gleason score.12,16
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We report the case of an incidental PC with normal PSA levels (PSA-negative PC) detected by FDG-PET in a patient referred to PET/CT scanning for staging of hypopharyngeal cancer.
2.21 ng/ml. Histology revealed a moderately to poorly differentiated adenocarcinoma infiltrating both lobes of the prostate with the main part in the right lobe and TNM stage pT3a, pN0, M0, R0, G 2–3 (according to WHO classification) and a Gleason score of seven.
Case report In 2003, a 63-year-old male patient with a history of hypopharyngeal cancer since 1997, underwent both clinical and biochemical screening for exclusion of PC. Both, serum PSA, with a level within the normal range (1.68 ng/ml; normal: 0–4 ng/ml) and rectal palpation of the prostate was not suspicious of a malignant process of the prostate. As such, no further evaluation was required and performed. Two years later, repetition of routine screening of the prostate again was inconspicuous with a serum PSA level (2.21 ng/ml) still within the normal range and no clinical signs of a mass in the prostate. At the same time, the patient was routinely referred to PET/ CT imaging for re-staging of the previously diagnosed hypopharyngeal cancer. PET/CT revealed no suspicious fluorodeoxyglucose (FDG) uptake indicating potential metastases of the hypopharyngeal cancer, but a small circumscribed uptake within the right-sided pelvis, caudal to the bladder (Figures 1a and 2a) indicating a pathological process within this region. The corresponding CT image failed to show any abnormalities (Figures 1b and 2b), but could localize the increased fluorodeoxyglucose (FDG) uptake in the right lobe of the prostate (Figures 1c and 2c). According to this finding, a PC was assumed and the patient underwent biopsy of the prostate, which confirmed the diagnosis of an adenocarcinoma. Consequently, a radical prostatectomy was performed. At the time of surgical resection, the PSA level was still within the normal range (1.9 ng/ml) and even declining from the formerly observed PSA level of
Figure 1 Coronary PET, CT and PET/CT images of a PSA-negative prostate cancer. White arrow: increased FDG uptake within the right lobe of the prostate. Scattered red arrow: no detectable lesion in the CT images (red arrow: see online version).
Figure 2 Transaxial PET, CT and PET/CT images of a PSAnegative prostate cancer. White arrow: increased FDG uptake within the right lobe of the prostate. Scattered red arrow: no detectable lesion in the CT images (red arrow: see online version). Prostate Cancer and Prostatic Diseases
Discussion We report the case of a patient with a PSA-negative and clinically inconspicuous PC, incidentally diagnosed by 18 FDG-PET/CT. This is a rare finding, as on the one hand, FDG-PET has been previously shown not to be appropriate for initial diagnosis of PC owing to several limitations, and should therefore not routinely applied for this purpose. On the other hand, PSA levels, usually the first step in the diagnostic cascade of PC, were within the normal range in this particular case. This has to be emphasized as these biochemical findings are sometimes unspecific and may also be found in patients with nonmalignant diseases of the prostate gland such as benign hyperplasia, prostatitis or even in healthy individuals.2–6,9,12–18 Even the described slight increase of the PSA level from 1.68 to 2.21 ng/ml after 2 years, which consecutively decreased to 1.9 ng/ml at the time of surgery, or a potential rise of the percent-free PSA in relation to total PSA, would not have required a prostate biopsy in any case as, despite the described rise of the PSA, PSA levels were still within and even not at the upper limit (4.0 ng/ml) of the normal range. In addition, estimation of percent-free PSA is also prone to variations between malignant and benign masses of the prostate.18 In contrast, as presented in this case, a ‘watchful waiting’ strategy would have been applied as well as a clinical evaluation of the patient, which still revealed neither significant signs of a mass in the prostate nor even symptoms of an enlargement of the prostate.19 Therefore, the malignancy would not have been diagnosed, if evaluation with 18FDG-PET/CT for re-staging of hypopharyngeal cancer with the incidental finding of an increased FDG uptake within the prostate would not have been performed as shown in this case. However, potential reasons for the incidental diagnosis of the PSAnegative PC by FDG-PET remain inconclusive. In most of the studies published previously, PSA levels were elevated and led to the suspicion of PC before further evaluation with, for example FDG-PET, had been carried out. As such, there is a lack of data regarding the diagnostic value of FDG-PET in PSA-negative PCs. The increased FDG uptake within the prostate in this specific case was surprising and has to be discussed owing to the well-known limitations and pitfalls of FDG-PET with a reported sensitivity as low as 4% in the diagnosis of primary PC.2 According to the present case, Melchior et al.20 found higher FDG accumulation in poorly differentiated PCs than in low grade prostate malignancies. In a further study, Oyama et al.21 examined 44 consecutive patients with histologically proven adenocarcinoma of the prostate. Twenty-eight of the 44 (sensitivity 64%) patients were visually positive, showing intermediate and high FDG uptake with a trend for FDG uptake in PC to correlate with the Gleason score. This is also in accordance with the present case, as histology revealed a high Gleason score of 7. However,
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previously published studies reported higher PSA levels in patients with PC with higher Gleason scores and lower grades of tumor differentiation, as well as aggressive course of disease.22,23 Consequently, the lower differentiation grade of the PC as well as the higher Gleason score in the present case are probably responsible for the increased FDG uptake but fails to explain the normal PSA level immediately before radical prostatectomy. If further histological or biochemical changes of the tumor cell may lead to diminished excretion of PSA and additionally to an increased FDG uptake remains a subject of debate. Furthermore, the introduction of the PET/CT technique seems not to improve the diagnostic value of FDG-PET despite adding morphological information to the metabolic data of PET.15 As a consequence, there is a great interest in several recently introduced radiotracers, for example 11C-choline, 11C-acetate and 11 C-methionine, which are currently evaluated in clinical studies for diagnosis of primary PC, recurrent PC, as well as metastatic disease owing to PC.12 Mainly 11 C-/18F-choline and 11C-/18F-acetate seem to be of value for the named indications and superior to FDG-PET, especially in the diagnosis of primary PC.6,12,24–30 However, as in some studies, a differentiation between benign hyperplasia from cancerous lesions of the prostate gland was not possible with for example 18Ffluorocholine PET/CT imaging, all of these tracers still need clinical evaluation with regard to their diagnostic value in PC.26
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Conclusion In this individual case, 18FDG-PET/CT was helpful in the diagnosis of a PSA-negative PC with a low grade of differentiation. Further studies must indicate whether 18 FDG-PET/CT may play a role in the diagnosis of PSAnegative PC besides PET/CT imaging with new promising PET-tracers like 11C-choline or 11C-acetate, which may become more important and available as a diagnostic tool for primary diagnosis of PC in the future. However, one has to be at least aware of a potentially malignant process in cases of an incidental FDG uptake in the prostate gland in 18FDG-PET/CT imaging performed for other reasons than diagnosis of primary PC as described in the present case of a patient with hypopharyngeal cancer.
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