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- Materials and Methods
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TRUS-guided prostate biopsy is the ‘gold standard’ for the diagnosis of prostate cancer. Over the past decade, several extended and saturation biopsy schemes [1-3] showing improved sensitivity for prostate cancer detection have been introduced; however, the optimal number and location of prostate biopsies is still debated . A major concern with transrectal biopsy is that even with newer biopsy schemes, the procedure may still miss ‘clinically significant’ prostate cancers, generally defined as those with tumour volume (TV) of ≥0.5 mL [5, 6]. Another concern is that the anterior portion of the gland, including the anterior peripheral (PZ) and transition zones (TZ) is difficult to target by standard transrectal biopsy, in particular with larger glands .
While many studies have evaluated the detection rate of prostate cancer for various biopsy schemes, including the transperineal approach, few have investigated the detection of clinically significant cancers using various biopsy schemes. In addition, the influence of biopsy cutting length and method of anterior gland sampling on the detection rate of clinically significant cancer in prostate glands of various sizes have hardly been evaluated.
Several studies have assessed simulated biopsy schemes using three-dimensional (3D) reconstructions of actual prostate cancer specimens [8, 9]. In these studies, the volume of multiple tumours could be analysed independently. As a 3D-prostate cancer model can more accurately identify: (i) the original tumour from which a positive simulated biopsy is taken and (ii) any tumours missed by biopsy, it is likely that properly constructed 3D-prostate biopsy simulations will have clinical relevance . However, the detection of clinically significant tumours and targeting of the anterior prostate have not been fully evaluated using a 3D-prostate cancer model. Using such a model, we evaluated various simulated biopsy schemes and investigated whether transrectal needle biopsy can be optimised to detect prostate cancers with a TV of ≥0.5 mL.
- Top of page
- Materials and Methods
- Conflict of Interest
Over the past decade, a large number of studies have investigated the effect of biopsy scheme on prostate cancer detection rate [1-3]. However, none of these studies revealed how many cancers were missed by the schemes investigated and most did not determine the detection rate for clinically significant cancers (TV of ≥0.5 mL). The present study, which analysed 800 tumours from 109 prostates, investigated all simulated biopsy cores individually using a 3D model such that both detected and undetected tumours could be calculated using the various biopsy schemes. Although we investigated only 109 patients, all of whom were initially diagnosed with prostate cancer by transrectal biopsy, the 3D model enabled study of many more tumours in the anterior PZ and TZ than would have been detected by the clinical biopsy session alone. Therefore, the implications of the present study may address current concerns about transrectal biopsy including detection of clinically significant tumours and targeting of the anterior prostate.
Herein, we further confirm the notion that increasing the number of biopsy cores can increase the detection of tumours but also show that the detection of tumours with a TV of ≥0.5 mL plateaued at 12-core biopsies in schemes without ADBx cores. This result is consistent with those of several other studies that have compared the detection rate for various schemes [1, 12, 13] and found 12 cores to be optimal and most effective. However, the present findings go further, showing that 21 of 90 (23%) tumours with a TV of ≥0.5 mL were missed by a 12-core scheme without ADBx cores, using 17-mm biopsy cutting length. The overwhelming majority (20 of 21) of these undetected tumours originated in the anterior prostate, either anterior PZ or TZ, strongly suggesting that adding biopsies directed to these regions coupled with longer cutting length may increase the detection of tumours.
The present study also shows that simulating deep ADBx proved beneficial in increasing the detection rate for tumours with a TV of ≥0.5 mL. A recent reconsideration of prostate anatomy showed that the PZ encompasses the posterior, lateral, and majority of the anterolateral tissue in the normal prostate gland . This is especially true for the apex where the PZ constitutes nearly all glandular tissue in the region. In recent years, we and other authors have reported that anterior-predominant tumours are increasingly common [15-17]. Al-Ahmadie et al.  analysed a large series of dominant anterior tumours and reported that more (49%) were of anterior PZ origin than of TZ origin (36%). They further highlighted the finding that anterior fibromuscular stroma, a region likely to be sampled by the ADBx cores simulated in this study, is involved by ≈75% of TZ dominant tumours and ≈50% of anterior PZ tumours. This collective evidence suggests that biopsies of the anterior gland would be beneficial for increasing the detection rate. In the present study, deep ADBx cores were designed for both the TZ and the anterior PZ in an effort to decrease the number of undetected prostate cancer in this region.
Interestingly, we showed that adding two shallow ADBx cores does not increase the detection rate for tumours with a TV of ≥0.5 mL (compared with schemes without ADBx). Conversely, adding two deep ADBx cores increased the detection rate. The current trend in prostate cancer detection is to use extended prostatic schemes (10–12 core biopsies without TZ-directed cores) as the initial biopsy strategy . Several studies have suggested that including TZ-directed core(s) at the time of initial biopsy is of little value, while others argue for the use of TZ-directed biopsies only in patients with prior negative biopsies and persistently elevated serum PSA levels [12, 18, 19]. The method of obtaining TZ cores is not well defined in many studies, although Fleshner et al.  described TZ biopsies obtained by triggering the gun once the needle had been advanced to the junction of the PZ and TZ. In the single study to correlate positive TZ-directed biopsy cores with findings at RP, Haarer et al.  reported that such biopsies uncommonly sample clinically relevant prostate cancer from the TZ. To our knowledge, no study has thus far assessed the depth of TZ or ADBx cores in transrectal biopsy. The present results indicate that depth of ADBx, using the difference of anterior–posterior diameter and biopsy cutting length to determine the distance to advance the biopsy needle before triggering, might significantly affect the efficacy of such cores. These findings imply that more attention paid to the depth of ADBx may well reduce the incidence of clinically significant tumours missed in the anterior PZ and TZ.
The role of prostate volume in choosing an appropriate biopsy scheme remains controversial . Several studies have shown a significant inverse relationship between the cancer detection rate and prostate volume [22-24]. Similarly, the present simulated biopsy findings confirm that an increase in prostate volume decreased the detection rate for tumours with a TV of ≥0.5 mL. However, it is not entirely clear how additional cores should be oriented in larger prostates to increase the detection rate. In the present study, we showed that adding ADBx cores to a standard 12-core scheme increased the detection rate for tumours with a TV of ≥0.5 mL and that this effect is maximised by increasing the number of ADBx cores in a prostate volume-adjusted fashion, supporting the results of a recent study . Although further investigation is necessary for prostates with a volume of ≥50 mL, the present results suggest that volume-adjusted ADBx would be beneficial.
Few prior studies compare prostate cancer-detection rate using different biopsy cutting lengths [26, 27]. Intuitively, a longer biopsy cutting length should improve prostate cancer detection. Fink et al.  compared the detection rate by an end-cutting technique (i.e. cores obtained at the tip of the biopsy needle) with 19- and 29-mm cutting lengths and concluded that a 29-mm cutting length led to a significant improvement in cancer detection. However, most of the biopsy instruments on the market are suitable for biopsies of 17- to 22-mm cutting length and conventionally operate with a side-cutting technique . In the present simulation, we showed that increasing the cutting length resulted in increased detection rates for tumours using a 12-core scheme and that the detection rate plateaus at 22-mm cutting length for detection of tumours with a TV of ≥0.5 mL. At that longer biopsy cutting length, adding volume-adjusted deep ADBx cores can aid in detection of nearly all (95%) tumours with a TV of ≥0.5 mL. It is intriguing to note that Moussa et al.  have shown that adding two extreme anterior apical biopsies to a standard 12-core biopsy achieves the highest rates of cancer detection when compared with ≤12-cores schema. This approach may be akin to the present simulated ADBx cores directed toward the apex, which were shown to increase detection of clinically significant prostate cancer.
In recent years, several groups have reported that a transperineal biopsy approach may result in a significantly higher prostate cancer detection rate than the standard transrectal approach, especially for anterior tumours [7, 30-32]. However, little data is available about the efficacy of transperineal biopsy for detecting prostate cancer with a TV of ≥0.5 mL and the transperineal approach may have increased association with adverse effects, e.g. urinary retention, erectile dysfunction, bleeding and LUTS, when compared with transrectal biopsies. The present study, while using biopsy simulation, strongly suggests that transrectal biopsy has the potential to detect nearly all prostate cancers with a TV of ≥0.5 mL. Yet, there are some limitations to the present study. While we showed an ‘optimal’ simulated-biopsy scheme, our conclusions are based on only 109 RP specimens. To validate this simulated scheme, it may be necessary to apply the present findings to an additional set of computer-modelled prostate phantoms. Furthermore, at least one recent study has suggested that biopsy schemes applied in virtual models will not necessarily produce equivalent results when applied in the clinic. Han et al.  have reported how poorly freehand prostate biopsy patterns compare with planned patterns and advise that robot assistance for TRUS needle biopsy may improve and standardise these biopsy schemes in the clinic. Overall, robust clinical investigation of these proposed biopsy schemes with correlation to pathological outcomes at RP will be necessary to confirm the present findings.
In conclusion, the present 3D-prostate cancer model analysis suggests that nearly all prostate cancer with a TV of ≥0.5 mL can be detected by 14–18 cores in TRUS needle biopsies. Longer biopsy cutting length and the use of deep ADBx cores (including the TZ) adjusted for prostate volume will be necessary to maximise detection.