Positron emission tomography/computed tomography-guided percutaneous trans-pararectal space prostate biopsy for the diagnosis of prostate cancer: A retrospective study

Background: Biopsy is considered the gold-standard technique for prostate cancer diagnosis and is recommended in patients with a high clinical indication of prostate cancer. In this study, we aimed to determine the diagnostic efficacy of a novel positron emission tomography (PET)/computed tomography (CT)-guided percutaneous trans-pararectal space-based approach to targeted prostate biopsy. Methods: PET/CT-guided percutaneous trans-pararectal space prostate biopsies were performed in 14 consecutive patients with indications of prostate cancer. Whole-body 18F-FDG PET/CT indicated the presence of 18F-fluorodeoxyglucose (FDG)-avid focal prostate lesions. Two tissue specimens were obtained from each patient. The final diagnoses were established based on the results of a histopathological analysis and clinical follow-up, and these findings were used to verify the diagnostic accuracy of 18F-FDG PET/CT for prostate cancer. Results: The diagnostic accuracy of 18F-FDG PET/CT for prostate cancer was 81.8%. Further analyses of the two biopsied samples per patient led to confirmed histopathological and immunohistochemical diagnoses of prostate cancer in all 14 patients. Consequently, the success rate of PET/CT-guided percutaneous trans-pararectal space prostate-targeted biopsy for the diagnosis of prostate cancer was 100.0% (14/14). Regarding safety, the average duration of biopsy was 20 min, and no serious complications occurred. Conclusions: PET/CT-guided percutaneous trans-pararectal space prostate biopsy may yield a new approach to targeted prostate biopsy for the diagnosis of prostate cancer. Moreover, this biopsy procedure can be performed safely without complications, and is more cost-effective than conventional trans-rectal and trans-4

perineal prostate biopsy methods.

Background
Prostate cancer is an important cause of morbidity and mortality in men worldwide [1]. In China, the incidence of prostate cancer has been increasing by approximately 12% annually. However, approximately 70% of patients present with locally advanced or extensively metastasised prostate cancer at the time of diagnosis [2][3]. Historically, trans-rectal ultrasonography (TRUS) of the prostate has remained the cornerstone of prostate cancer diagnosis since the period of systematic 'sextant' biopsy of suspected prostate malignancy, wherein 3 cores are obtained from each side of the prostate [4][5][6]. In men undergoing an initial prostate needle biopsy consequent to an elevated serum prostate-specific antigen (PSA) level, systematic 12-core TRUS-guided prostate biopsy yields cancer detection rates of 28-52% [7][8][9][10][11][12][13]. The systematic sampling of all prostatic quadrants improves the accuracy of sampling. However, this method has been criticised for its oversampling of insignificant tumours, the risk of additional morbidity and the need for general anaesthesia.
Compared with traditional biopsy protocols such as systematic 12-core TRUS-guided biopsy, multiparametric magnetic resonance imaging (MRI)/ultrasonography-guided biopsy yields more refined diagnostic information [14][15][16]. The minor complications of the trans-rectal and trans-perineal biopsy procedure include haematuria, rectal haemorrhage, haemospermia, vasovagal attack, and pathogenic infection. TRUSguided prostate biopsy is associated with additional major complications, including sepsis, bleeding or other complications requiring hospitalisation. More importantly, an increased risk of life-threatening septic shock was reported with trans-rectal biopsy [17]. Therefore, a safer and more effective algorithm for the diagnosis of prostatic diseases should be explored. Recent [18][19][20]. In our previous study, we proved the efficacy of PET/CT-guided targeted biopsy for the evaluation of advanced lung cancer with metastatic bone lesions, for surveillingthe surveillance of molecular subtype switching of in metastatic breast cancer cells and identifying the identification of bone marrow involvement in newly diagnosed cases of lymphoma [21][22]. However, no studies have examined the utility of PET/CT-guided targeted biopsy for prostate pathologies. In this study, therefore, we evaluated the safety and efficacy of PET/CT-fusion-guided percutaneous trans-pararectal space prostate biopsy for the diagnosis of prostate cancer.

PET/CT and image interpretation
The patients were asked to fast for at least 4 hours before undergoing 18 F-FDG PET/CT to ensure a normal blood glucose level (70-120 mg/dL) before the intravenous injection of 18 F-FDG. Each patient received an intravenous injection of 370-666 MBq (10-18 mCi) of 18 F-FDG. Data were acquired using a PET/CT system (Discovery STE; GE Medical Systems, Milwaukee, WI, USA) at 45 min post-injection.
The following procedure was used to acquire data First, a CT scan was performed from the head to the pelvic floor, using the following settings: 110 kV, 110 mA, tube rotation time of 0.5 s, and 3.3-mm scan section thickness. These settings were matched to the PET settings. Immediately after the CT scan, a PET scan was performed to obtain a transverse field of view identical to that obtained by CT.  Table 3).

Multiple primary tumours in patients with prostatic lesions
Simultaneous PET/CT-guided biopsies of the prostate and other organs were performed in 57.1% (8/14) of the patients with prostatic lesions. The incidence rate of multiple primary tumours was 28.6% (4/14). The patients' characteristics are summarised in Table 1.

Biopsies of primary prostate and bone lesion
Simultaneous PET/CT-guided prostate and bone lesion biopsies were performed in 28.6% (4/14) of the patients. Histopathological examinations confirmed the presence of metastatic bone lesions in patients with prostate cancer ( Table 1).

Complications of targeted prostate biopsy
Each targeted prostate biopsy required an average of approximately 20 minutes.
Slight bleeding and pain were experienced by almost all patients who underwent the biopsy. However, no serious complications were noted. Moreover, no complications associated with rectal puncture injury occurred in the patients who underwent prostate biopsy (Table 4).

Discussion
According to the 2015 Annual Report of the National Central Cancer Registry (China), the overall incidence of prostate cancer was 7.1/10 5 individuals in 2011.
Accordingly, prostate cancer was the ninth most prevalent cancer overall, and seventh most prevalent among men [23]. However, the majority of patients with prostate cancer were diagnosed at an advanced disease stage. Early diagnosis is a key driver of improved survival among men with prostate cancer in China. Organconfined prostate cancer at the time of diagnosis is associated with a good prognosis and a favourable response to curative therapy [24]. Conversely, metastatic prostate cancer is associated with a poor prognosis, and skeletal metastasis is associated with a 5-year survival rate of <30% [25].
In the present study, 13 patients presented with indications of prostate cancer, including an elevated PSA level and/or abnormal digital rectal examination and/or imaging findings. One patient had been treated previously for prostate cancer.
According to the 18 F-FDG PET/CT findings, 6 patients (66.7%) with prostate cancer had skeletal metastases, and 1 patient (11.1%) presented with a tumour that was no longer organ-confined and had invaded the bladder. The incidence rate of multiple primary tumours among patients with prostate cancer was 28.6% (4/14).
Improvements in cancer care have been linked closely to advances in imaging technologies, as these improvements enable a more accurate diagnosis, staging, and surveillance of disease. PET/CT recently emerged as a promising diagnostic imaging platform for both primary and recurrent prostate cancers [26]. In addition to 18 F-FDG, routine clinical imaging procedures use various radiolabelled tracers [e.g., 18 F-choline, 18 F-NaF, 68 Ga-prostate-specific membrane antigen (PSMA), 68 Ga-DOTATATE, 18

F-FACBC] with demonstrated efficacy for cancer diagnosis in various
clinical settings [26][27]. Newly developed tracers exhibit increased accuracy for the detection of small, incipient metastatic foci [28][29]. Improvements in MRI techniques, and particularly in functional imaging, have enabled radiologists to play an important role in the risk stratification and management of patients [30][31][32]. 18 F-FDG PET/CT is primarily useful in the diagnosis and staging of prostate cancer because it combines the metabolic information of PET with the anatomic information of CT. Moreover, whole-body scanning facilitates the detection of primary tumours in multiple organs. Additionally, 18 F-FDG PET/CT can accurately diagnose cancer recurrence. In this study, prostate cancer was confirmed via histopathological examinations in 9 of 14 patients, whereas the remaining 5 patients had benign lesions (including 2 misdiagnoses of prostate cancer). The diagnostic accuracy of detected multiple primary tumours that were confirmed pathologically as prostate cancer in 4 patients (28.6%). One of the 9 patients exhibited a tumour recurrence and metastatic bone lesion on 18 F-FDG PET/CT, which was eventually confirmed as prostate cancer.
Despite the enthusiasm surrounding the use of PET and MRI for diagnosing prostate cancer, prostate biopsy remains the gold-standard diagnostic option. Prostate biopsies have been used to diagnose prostate cancer since the beginning of the last century [5][6]. Ideally, prostate biopsy should be minimally invasive with few side effects, and should identify a large proportion of men who would benefit from treatment while minimising the identification of men with clinically insignificant cancer to prevent over-treatment. Although the optimal method of prostate biopsy remains controversial, TRUS-guided biopsy is the most widely accepted method for the diagnosis of prostate cancer. Greyscale TRUS has a low sensitivity and specificity for prostate cancer detection, and some studies reported low detection rates for saturation prostate biopsy via the trans-rectal or trans-perineal route (21.7-45% [33][34][35][36] and 22.7-42.2%, respectively [37][38][39]). Despite the advantages of TRUS-guided prostate biopsy, its invasive nature and rectal approach could potentially cause complications. Infectious complications ranging from asymptomatic bacteriuria to septic shock may occur during TRUS-guided prostate biopsy via the manipulation of infected prostate tissue, which also increases the risk of introducing the rectal flora into the prostate tissue, urine, and blood.
Here, we introduce a novel approach to prostate biopsy, namely 18  The histopathological analysis revealed that both the prostatic and pulmonary lesions had originated from the primary prostate tumour, whereas the bone lesions had metastasised from the lung lesion rather than the prostate tumour.
Before performing PET/CT-guided percutaneous 18 F-FDG-avid target biopsy, we selected the optimal puncture site based on the target location to ensure a favourable biopsy success rate and the optimal needle path to minimise trauma.
When selecting the target location, the site with the highest metabolic 18 F-FDG accumulation among all focal hypermetabolic prostate lesions was selected first, as such lesions would more likely represent the true cancer grade and would thus affect the clinical classification, staging, and prognosis. Other visible but controversial lesions were targeted thereafter.
The optimal needle path is extremely important when aiming to avoid puncturing the nearby blood vessels, spinal nerve trunk, and other vital organs. In our study, we chose the anatomically safer trans-pararectal space, rather than the trans-rectal or trans-perineal approach. This option can avoid the damage to the rectum or perineum associated with a conventional biopsy path, and may minimise the occurrence of complications. Altogether, we considered these factors to ensure a safe, feasible, and effective prostate biopsy procedure. 18 F-FDG PET/CT-guided percutaneous trans-pararectal space prostate biopsy is the third prostate biopsy technique worldwide that can accommodate all these factors simultaneously. This novel method can reduce the false-negative or false-positive rate and is a relatively safer and more effective way to obtain a pathological diagnosis.
In our study, a correct biopsy-assisted diagnosis was made on all cases. The diagnostic success of 18

Consent for publication
Not applicable.

Availability of data and materials
The datasets and materials used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Competing interests
The Biopsy diagnostic success rate: 100.0% (14/14) PET/CT, positron emission tomography/computed tomography  Representative 61-year-old male patient with prostate cancer. The patient was hospitalised w Figure 3 Representative 66-year-old male patient with prostate cancer. The patient presented with a 1