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International Journal of Urology (2015) 22, 146–151
doi: 10.1111/iju.12660
Review Article
Transperineal template-guided mapping biopsy of the prostate Arjun Sivaraman, Rafael Sanchez-Salas, Eric Barret, Youness Ahallal, Francois Rozet, Marc Galiano, Dominique Prapotnich and Xavier Cathelineau Department of Urology, Institute Mutualiste Monsouris, Paris, France
Abbreviations & Acronyms AS = active surveillance AUR = acute urinary retention PCa = prostate cancer PSA = prostate specific antigen RP = radical prostatectomy TPB = transperineal biopsy TRUS = transrectal ultrasound TRUS-B = transrectal ultrasound-guided biopsy TTMB = transperineal template-guided mapping biopsy TTSB = transperineal template-guided saturation biopsy Correspondence: Rafael Sanchez-Salas M.D., Department of Urology, Institute Mutualiste Monsouris, 42 Bd Jourdan, 75674 Paris Cedex 14, France. Email:
[email protected] Received 1 May 2014; accepted 24 September 2014. Online publication 25 November 2014
146
Abstract: Accurate diagnosis of prostate cancer has eluded clinicians for decades. With our current understanding of prostate cancer, urologists should devise and confidently present the available treatment options – active surveillance/radical treatment/focal therapy to these patients. The diagnostic modalities used for prostate cancer have the dual problem of false negativity and overdiagnosis. Various modifications in the prostate biopsy techniques have increased the accuracy of cancer detection, but we are still far from an ideal diagnostic technique. Transperineal template-guided mapping biopsy of the prostate is an exhaustive biopsy technique that has been improvised over the past decade, and has shown superior results to other available modalities. We have carried out a PubMed search on the available experiences on this diagnostic modality, and along with our own experiences, we present a brief review on transperineal template-guided mapping biopsy of the prostate. Key words: mapping biopsy, prostate biopsy, prostate cancer, template guided biopsy, transperineal biopsy.
Definition The Ginsburg study group defines TTMB of prostate as “exhaustive transperineal TRUS guided biopsies of the prostate performed with the patient in lithotomy position using a 5-mm brachytherapy grid, with at least one biopsy from each hole” and TTSB as “more than 20 transperineal TRUS guided biopsies of the prostate performed with the intention of comprehensively sampling the prostate, according to a predefined core distribution pattern”.1 As different techniques are being used at various centers, these standard definitions will aid in uniform reporting, and avoiding miscommunication and confusions.
Background In developed countries, PCa is the most common solid organ tumor and third most common cause of cancer-related mortality.2 Although PSA screening and testing has shown reduction in PCa mortality, it detects both indolent and aggressive tumors.3 Contemporary TRUS-B used for the diagnosis of PCa have been shown to miss 25–30% cancers.4–7 In contrast, long-term follow-up studies on PCa have shown the number of patients required to be screened and treated to avert one PCa-related death is as high as 1055 and 37 patients, respectively.3 Hence, we face the dual challenge of false negative biopsies, and among the patients with cancer, possible overdiagnosis and overtreatment. Extended and saturation biopsies can reduce the false negative rate, and incorporation of image-guided biopsies can possibly reduce the overdiagnosis.8 However, reduction of overtreatment requires active surveillance protocols/focal therapy to treat low-risk PCa. To safely assign patients to AS/focal therapy, we require a reliable biopsy technique that can precisely characterize the lesion in terms of grade, volume, location and organ-confined stage. Clinical studies have shown that although saturation biopsy increases the diagnostic yield, its accuracy to characterize the lesion is similar to standard 10- or 12-core biopsy.9 TPB techniques are safe and efficacious alternatives to transrectal biopsies. Different techniques of TPB have been reported in the literature, varying in number and distribution of cores, showing results better than TRUS-B. The biomechanical facets of the random sampling technique in both TRUS and TPB are liable to unsystematic and uneven sampling of all the areas of the prostate. This problem can be overcome by using a biomedical engineering approach – uniform grid sampling technique.10 Barzell and Whitmore introduced the TTSB scheme, using a brachytherapy grid and dividing the prostate into 24 zones.11 Later, Crawford et al. proposed a © 2014 The Japanese Urological Association
Transperineal mapping biopsy of prostate
unique technique of TPB, 3-D TTMB of the prostate, using computer simulations on autopsy and RP specimens.12 In this technique, multiple transperineal biopsies were carried out, spaced at 5-mm intervals, throughout the volume of the prostate, and high degree of accuracy and sensitivity for detecting cancer was shown. Onik and Barzell reported their 4-year experience of this volume-based technique in clinical practice, and showed superior sensitivity and staging information as compared with TRUS-B.13 In the present review, we focus on the present technique, indication and outcomes of TTMB. Future studies will provide better evidence on optimal technique, its position in the algorithm of PCa diagnosis and follow up, and its use in image fusion studies.
Rationale TRUS-guided 10- or 12-core biopsy is the standard diagnostic modality for men with suspected PCa. Saturation biopsy is used in the setting of negative initial sextant biopsy and a high index of suspicion of cancer. These procedures are carried out at outpatient clinics with local anesthesia under the cover of antibiotics. The procedure is generally well tolerated by the patients, with a decreasing acceptability noted in younger patients and on repeat biopsies. The major limitations of TRUS-B are infection, false negativity and inability to precisely characterize the cancer. These limitations might be inherent to the transrectal approach of prostate biopsy, and might not be reduced by increasing the number or changing the distribution of cores taken during the biopsy. Urosepsis is a notable complication of TRUS-B, with 1.3% patients requiring hospitalization.14 Increasing reports of quinolone-resistant intestinal flora and inadequate prostatic tissue penetration by antibiotics are concerning issues in the prophylaxis and treatment of these patients.15 Shen et al. in their systematic review reported a similar incidence of infection in TRUS-B and TPB.16 However, 24-core biopsy was the highest number of cores taken in all the studies included in that review. Extensive sampling involved in mapping biopsy techniques, if carried out transrectally, can produce considerable rectal injury and significant bacterial translocation. The transperineal route will be logically safe, as the needle passes through the cleaned perineal skin rather than bowel or feces. However, this advantage of TPB needs to be proved in future randomized studies. The cancer detection rate of 10- or 12-core TRUS-B from contemporary series is 20–35%, and it increases to 30–40% with saturation biopsies.16 TTSB and TTMB carried out after initial negative TRUS-B detects cancer is 35–68%17 and 68.8%18 of patients, respectively. Bittner et al. reported a high cancer detection rate of 73.3% when TTMB was used as initial biopsy to establish the diagnosis.19 The possible rationale for these superior results of TPB are as follows. TRUS-B has inherent physical and technical limitations to the biopsy transition zone and anterior regions of the prostate, whereas TPB can sample these regions similarly to other regions. The needle in TPB is parallel to the prostate rather than perpendicular as in TRUS-B, and hence more tissue is sampled in every core. TRUS-B is more prone to inaccuracies in mapping and sampling when using unstabilized manual positioning of the guide needle and relying on the 3-D visual recall for guidance. More importantly, exhaustive biopsy protocols, such as TTMB, which © 2014 The Japanese Urological Association
involves multiple biopsies using a uniform grid, can technically miss only those tumors that are smaller than the distance between the adjacent cores. For instance, if the distance between the adjacent cores is 0.5 mm, TTMB can miss only those tumors that are smaller than 0.5 mm and located exactly in the area between adjacent cores. Accuracy of TRUS-B in characterizing the lesion is disappointing. Large series have shown that Gleason upgrading from TRUS-B to RP specimen is 29%, and it improves to 20% when 10-core biopsy was carried out.20,21 Onik and Barzell reported a Gleason upgrade of 23% from TRUS-B to TTMB, which is similar to the upgrading noted in RP specimens.13 Bittner et al. used TTMB to approximately map the location of cancer within the prostate, and proposed that theoretically the 12-core TRUS-B scheme would have missed 23.7% of these cancers, and 18% of the cancers would have been wrongly reported as low Gleason.19 Crawford et al. studied the clinical–pathological correlation of TTMB with 3-D reconstruction of RP specimens, and showed that 72% of the TTMB cores were identical in grade to RP specimens and 80% accuracy in predicting laterality.12 These data show that TTMB is more accurate in predicting the tumor characteristics than TRUS-B. This accuracy is very important in the present era where much emphasis is on AS/focal therapy, because current AS criteria based on TRUS-B often misses unfavorable cancer, and focal therapy requires confirmation of unifocal tumor. More prospective studies comparing TTMB with RP specimens will further validate the accuracy of TTMB. Another advantage of TTMB is in postradiotherapy biopsy, where the incidence of rectal complications are high with TRUS-B, and in patients at high risk of infection, such as diabetes mellitus patients, those in an immunocompromised state, recent overseas travellers and those with prior antibiotic use.17 The downsides of TTMB as compared with TRUS-B are the need for general anesthesia, the large number of cores to be examined and the possible increased complication associated with the higher number of cores. A more concerning aspect of this extensive biopsy protocol is the increased possibility of detecting clinically insignificant tumors that could further result in overtreatment. Crawford et al. observed a 36% downgrade of Gleason score from TTMB cores to RP specimens. However, there is very scarce literature available to precisely quantify this problem and the definition of insignificant cancer in TTMB has to be cautiously assessed to reduce the downgrade/downstage in prostatectomy specimens. Table 1 compares TRUS-B and TTMB.
Indication TTMB is an elaborate procedure with superior results compared with the other diagnostic techniques. The current indications for carrying out TTMB are as follows.
Prior negative TRUS-B Patients with previous transrectal negative biopsy and with risk factors, such as rising total PSA, falling free PSA, strong family history, previous atypia or high-grade prostatic intra-epithelial neoplasia, are at high risk of harboring cancer. The cancer 147
A SIVARAMAN ET AL.
Table 1
Comparison of TRUS-B and TTMB TRUS-B
Route Anesthesia No. cores Cost (approximately) Duration of the procedure Cancer detection rate Upgrading/upstaging Complications
Transrectal Transperineal Local Regional/general Fixed based on the protocol used. Usually 12–24 cores Depends on the gland size. Usually 40–70 cores 400 Euro 650 Euro 20–30 min 45–60 min 20–40% Primary – 73.3%, prior negative biopsy – 68.8% 20–50% 8–10% Complications of TTMB are comparable with TRUS-B except for AUR, which is higher in TTMB (10–39% vs 2–10%)
detection rate of TTSB and TTMB after initial negative TRUS-B is shown in Table 1, which is much better than the detection rate of saturation TRUS-B. One of the concerns in this group of patients is that cancer in the antero-apical region of the prostate, which is being missed by transrectal biopsy. The combination of an aggressive and anterior tumor known as prostatic evasive anterior tumor syndrome (PEATS) manifests as a rising PSA in the setting of a prior negative TRUS-B.22 Gershman et al. have reported 94.1% of the cancers detected by TTSB after a prior negative TRUS-B are in the apical and anterior regions of the prostate.23
AS PCa is a multifocal disease. Patients with minimal low-grade cancers as met by the Epstein criteria can be managed with AS. We need a reliable biopsy technique that can accurately exclude high-grade cancer in other regions of the prostate. The present evidence has shown that when patients with PCa on AS based on TRUS-B findings underwent TTSB/TTMB, upgrading (Gleason/volume upgrade) was noted in up to 30% of the patients (Table 2). In the Institute Mutualiste Montsouris, Paris, France, we noticed that TTMB upstaged 30.6% of patients with TRUS-B diagnosed low-risk PCa. TTMB appears to better characterize the cancer within the prostate compared with other biopsy techniques.
Focal therapy Pathological studies of RP specimens have showed that 20–25% of patients had single index cancer only, and 40–60% had single index cancer with an additional small (less than 0.5 mL) clinically insignificant cancer.42,43 Based on these data, focal therapy can be tried for low-grade single index tumors to avoid the overtreatment of RP. The success of focal therapy depends on proper patient selection in whom the clinically significant cancer is confined to a single location. Standard/sextant TRUS-B or magnetic resonance imaging with or without spectroscopy failed to adequately stage the patients for focal therapy.44,45 TTMB have shown superior staging information for focal therapy as shown by Onik et al. and Barzell et al.13,40,41 Further research on the balance of cost, complication and the diagnostic yield will define the future indications of TTMB in primary biopsy setting and image fusion studies.
Technique Several techniques of TTMB have been described varying in the number and distribution of cores. All patients are ensured of 148
TTMB
sterile urine before the procedure. Routine use of tamsulosin in the periprocedure period can prevent acute urinary retention.46 Prophylactic antibiotics are used to prevent infection. Logically, antibiotics should be aimed at both bowel and skin pathogens. Biopsies are carried out by a single operator in the dorsal lithotomy position under general anesthesia. A Foley catheter might be placed to identify the location of the urethra and also to assess hematuria. A standard brachytherapy grid with holes 5-mm apart, as shown by Barzell and Whitmore, is used as a template.11 The rationale of using a 5-mm grid is that any cancer less than 5 mm might not be clinically significant.47 To accurately mark the location of each core, grid co-ordinates A-M are placed in the x-axis and 1–12 in the y-axis, and the co-ordinate D2 is positioned in the midline corresponding to the urethra. All the biopsy cores are named according to the co-ordinates, and if more than one core is taken from a single hole, an additional tag as proximal (apex) or distal (base) is used. The grid is attached to a cradle and firmly positioned against the perineum. A standard transrectal probe with a 5–7.5-MHz transducer is introduced, and the prostate is scanned from the base to apex and the volume calculated by the prostate ellipsoid formula (height × length × width × pi/6). Biopsies are carried out with an 18-G automated biopsy gun. The position of the biopsy gun during the biopsy is tracked through the TRUS probe, and it is ensured that the whole length of the prostate is biopsied. Care should be taken to avoid injury to the urethra and the region of the bladder neck. Biopsies in the midline are taken only posterior to the urethra to avoid injuries. All the biopsy containers are appropriately tagged, and each core should be reported for core length, presence of cancer, Gleason grade, cancer length and ratio of cancer-to-core length. Patients are discharged from hospital care on the same day unless there are complications.
Total number of cores Barzell and Whitmore originally proposed the biopsy technique for TTMB in which the prostate is divided in into the proximal and distal half. Each half is again divided into four parts as anterior/posterior and right/left. Furthermore, each octant is divided into three zones (medial, intermediate and lateral). This results in 24 zones, and one to three biopsies are taken from each zone.11 Later, Onik and Barzell in their PCa mapping study followed a different technique in which at least one biopsy was taken in each aperture of the template throughout the volume of the prostate, and hence the number of biopsies is directly proportional to the volume of the gland.13 Recently, the Ginsburg © 2014 The Japanese Urological Association
© 2014 The Japanese Urological Association
485
87 191 98
414
Bittner et al. (2013)29
Losa et al. (2013)30 Bittner et al. (2013)19 Our experience (2013)
Huo et al. (2012)31
96
215
140 373
180 80
110
106
Barqawi et al. (2011)18
Abdollah et al. (2011)38 Taira et al. (2010)39
Onik et al. (2009)40 Barzell and Melamed (2007)41
Onik and Barzell (2008)13
Crawford et al. (2005)12
40 101
69
107
Lecornet et al. (2012)37
Pal et al. (2012)35 Ayres et al. (2012)36
Dimmen et al.
(2012)34
Hu et al. (2012)33
Mabjeesh et al. (2012)32
92
270 25
Gershman et al.
Ekwueme et al. (2013)27 Crawford et al. (2013)28
409
Symons et al. (2013)26
34
50 634
Klatte et al. (2013)24 Vyas et al. (2013)25
(2013)23
No. patients
Computer simulation of autopsy and RP specimen
Retrospective
Prospective Prospective
Prospective Prospective
Computer simulation of RP specimen Prospective
Prospective Prospective
Computer simulation of RP specimen Prospective
Prospective
Retrospective
Prospective Prospective Retrospective
Retrospective
Prospective Retrospective
Retrospective
Prospective
Prospective Retrospective
Design
Overall literature review of TTSB and TTMB
Study
Table 2
63.1
–
68.2
66.4 63.8
60.5
63 68
64.5
61
63.8
60.9
63.9 64.6 63
64.8
64 66
66.2
63
57.5 63
Mean age (years)
7.4
16.5
10 8.3
4.8
2.1
21.9 6.4
25.2
8.5
14.1
7.7
6.9 5.2 6.3
8.7
10 5
23.6
9.69
7.3 7.66
Mean PSA
Autopsy – 86, RP specimen – 20
Focal therapy
Active surveillance Focal therapy/active surveillance
Active surveillance – 180 Prior negative TRUS – 35 Prior negative TRUS Primary – 79 Prior negative TRUS-B – 294
–
Prior negative TRUS-B Active surveillance
Prior negative TRUS-B
–
Prior negative TRUS-B
–
Focal therapy Primary Active surveillance
Prior negative TRUS-B
Prior negative TRUS-B Correlation of TTMB and RP specimen
Prior negative TRUS-B Prior negative TRUS-B – 174 Primary – 153 Active surveillance – 307 Primary – 273 Repeat – 136 Prior negative TRUS-B
Indication
–
50.2
50 66.3
24 54
56
36 47
18.4
55
33.3
23.5
42.3 54 24
59
28 49
24.8
19
24 31
Mean no. cores
Template-guided mapping
Template-guided mapping
Template-guided mapping Template-guided saturation
Template-guided saturation Template-guided saturation
Template-guided mapping
Template-guided mapping
Template-guided saturation Template-guided saturation
Template-guided saturation
Template-guided mapping
Template-guided saturation
Template-guided saturation
Template-guided saturation Template-guided saturation Template-guided mapping
Template-guided saturation
Template-guided saturation Template-guided mapping
Template-guided saturation
Template-guided saturation
Template-guided saturation Template-guided saturation
Technique of TPB
Autopsy – 86%, RP specimen – 100%
–
25.70% Primary – 75.9% Prior negative TRUS-B – 43.7% – –
–
23%
22.70% 16%
– –
27.20%
–
100% (for lesions > 0.5 ml) 68.80%
– 34%
–
–
–
25.60%
29.60% – 16.30%
–
– –
–
–
– 29%
Gleason upgrade
68% –
55%
–
26%
–
– 73.30% –
46.60%
55% –
48% Prior negative TRUS-B – 36% Primary – 54% Primary – 64.4% Repeat – 35.6% 50%
Cancer detection rate
Upstaging noted in 61.1% patients TTSB detected cancer in 47% patients with negative repeat TRUS-B Bilateral disease found in 55% patients who had unilateral disease in TRUS-B
The upgrade includes both Gleason and volume upgrade 7% of lesions 0.2 – 0.5 ml were missed by TTMB Upstaging noted in 45.6% patients
Final RP specimen showed majority anterior tumors
11.4% insignificant cancer 9.1% had bilateral disease, 5% had both Gleason and volume upgrade Sensitivity – 48% and specificity – 84.1% for TTSB in this accuracy study 83.3% cancers in the anterior zones TTMB had accuracy of 0.9
Significantly higher detection rates were found in prostates
