Interpretation of Prostate Needle Biopsies
Case 1 -
Sampling Considerations in Prostate Needle Biopsies
Rajal Shah and Ming Zhou
A 51-year-old African American men had a serum PSA 4.5 ng/ml in June 2004. The
patient underwent a sextant biopsy, which revealed multifocal HGPIN. After 6 months, he underwent a
repeat biopsy with an "extended biopsy template" of 12 cores with a diagnosis of prostate adenocarcinoma,
Gleason score 3+4=7.
Contemporary Needle Biopsy Sampling Considerations in the Diagnosis of Prostate Cancer
Recent changes in the pathological parameters of prostate cancer in PSA screening era
The profile of newly detected prostate cancer has significantly changed due to wide spread utilization
of PSA testing after its introduction in the late 1980s . The "stage shift" has been the most
remarkable change, with a steady trend of detecting and treating earlier stage, smaller volume disease in
younger and healthier men . The diagnosis of prostate cancer now is mostly triggered by an
abnormal/rising PSA. This is reflected in the incidence of non-palpable cancers (stage T1C), which has
increased in proportion by seven-fold between 1988 and 1996, from 10% to 73% of all cancers detected
The traditional sextant biopsy
The evolution of prostate biopsies has rapidly changed over the past several years. In 1989, the
sextant prostate biopsy was introduced and rapidly became the standard over directed biopsies of
hypoechoic lesions and palpable nodules . This technique has dominated the earlier phase of
PSA era as the primary sampling approach for the prostate cancer detection. This technique primarily
utilizes paramedian (parasagittal) plane sampling approach directed towards base, mid and apex portion of
the prostate bilaterally (Fig 1 and 2A). Little was done regarding the refinement of this technique
until, recently Stamey suggested moving the biopsies more laterally to better sample the anterior horns
of peripheral zone . This recommendation was supported by the zonal anatomy of the prostate
as well as origin of the tumor . It became clear that the majority of prostate cancers
(approximately 80%) originated in the peripheral zone and thus some investigators began exploring
alternative systemic biopsy schemes to more extensively sample the peripheral zone and thus improve the
cancer detection rate. As with any situation that involves sampling, the possibility of sampling error
exists. This notion was supported in prostate biopsy series by a study demonstrating an inverse
relationship between prostate gland size and cancer detection rates as determined by sextant
Fig 1: Sextant Biopsy Approach:
Fig 2A and B: Cross section of prostate with A= Paramedian sextant approach and B=laterally directed biopsy approach for extended scheme, TZ= Transition Zone, PZ=Peripheral Zone
In recent years, it has become increasingly evident that the sextant biopsies could miss up to 30% of
Daneshgari et al in a computer simulation model suggested that sextant biopsies,
although an improvement, would still miss many cancers as only 20% of prostates had a tumor distribution
which would be detected with the paramedian template, which is utilized by the sextant approach
. Furthermore, other investigators have demonstrated that sextant protocol in particular
tends to under-sample certain areas of the prostate such as "anterior horns" and the lateral aspects of
the peripheral zone, where majority of prostate cancer are distributed
small tumors seem to concentrate more along the sub capsular distribution along the dorsolateral part of
Contemporary sampling approaches:
1) Extended Biopsy template
Based upon these observations, others have advocated the use of an extended pattern technique at
initial prostate biopsy in order to further increase the likelihood of detecting cancer. Extended biopsy
pattern is typically defined as essentially a sextant template, with at least four additional cores from
the lateral peripheral zone (Fig 2B), and also biopsies directed to lesions found on palpation or
imaging . Eskew et al first advocated an extended pattern, finding a statistically
significant advantage (35% greater detection) with the additional cores of a 5 region biopsy
Of note, their template also included three biopsies from the midline at the apex,
mid-gland and base besides four laterally directed biopsies, however only few cancers were detected by 3
centrally placed biopsies. With their 11 site pattern technique, Babaian et al detected 31% more cancers
at initial biopsy compared to the sextant biopsy approach . Their template included
additional cores from the midline, transitional zones, and two cores from the anterior horns.
More recently, Gore et al evaluated a 12-core biopsy scheme in 396 patients, of which 67% were first
time biopsy patients . A standard sextant scheme was combined with a laterally directed
sextant scheme at the apex, mid and base bilaterally. The cancer detection in this group was 42%.
Standard sextant biopsy would have detected only 71% of the cancers and importantly, the lateral sextant
biopsy scheme along with the apical and base biopsies from the standard sextant scheme detected all of
the cancers in this subgroup.
We have utilized extended biopsy technique as the initial prostate biopsy approach to demonstrate its
significance for detection of overall and clinically significant cancers . When potential
confounding factors were adjusted, the final multivariable regression models demonstrated a significant
independent effect of an extended pattern biopsy at initial setting with an overall odds ratio of cancer
detection of 1.55 (C.I. 1.09-2.19). To put this finding in clinical context, the Number Needed to Treat
(NNTT) based on the final models were derived. For every 10 extended pattern prostate biopsies
performed, one additional cancer was detected.
Comparison of various biopsy approaches
Presti et al retrospectively simulated various extended biopsy schemes and then compared to the
"gold-standard" 12-biopsy scheme (assuming it detects 100% of the cancers in the population). Following
rates were observed for various approaches as shown in figure 3 . They concluded that the
optimal biopsy scheme for initial biopsy patients is at least 10-core scheme as shown in last scheme of
Significance of prostate cancer detected in extended template
The goal of the prostate biopsy is to detect clinically significant cancers. Critics of the extended
prostate biopsy approach have used the theoretical argument that more clinically insignificant cancers
must, by definition, be detected using extended biopsy approach. However, no studies have substantiated
this argument. Eskew et al found that increased sampling of the prostate through extended biopsy
techniques does not increase the detection of potentially insignificant tumors; however it appears to
detect earlier stage cancer . Similarly, in our recent study, we have demonstrated that use
of extended biopsy was not found to be associated with increased detection of clinically "insignificant"
Significance of HGPIN and Atypical small acinar proliferation (ASAP) in extended biopsy practice
Moore et al addressed the prognostic significance of HGPIN and ASAP in the contemporary needle biopsy
setting. Based on their results, the significance of HGPIN as a predictive marker for prostate cancer in
repeat biopsy in the contemporary setting appears to be significantly less but the significance of ASAP
continues to be associated with a high risk of cancer. They concluded that patients diagnosed with HGPIN
in the initial extended biopsy setting may not warrant a repeat biopsy . This issue is
further addressed in detail in the later sections of PIN and ASAP.
Effect of extended biopsy approach on the Gleason grading of the prostate cancer
Recent studies have suggested that utilization of an extended biopsy sampling approach improves the
correlation between the biopsy and radical prostatectomy Gleason grading . It has also been
demonstrated to improve the reliability of biopsy Gleason grade in the setting of patients receiving
radiation therapy .
2) Saturation biopsy technique for repeat biopsy approach
Saturation biopsy is an uncommon extensive sampling approach, which is utilized in subsets of patients
with high index of clinical suspicion in which previous attempts are not diagnostic. Under anesthesia a
mean of 23 (range 14 to 45) saturation cores are obtained. Using an inward radial step approach,
prostates are biopsied starting at far lateral peripheral zone (anterior horn) and continuing until the
mid gland is reached. The process is repeated contra lateral side.
Stewart et al used this approach to evaluate 224 patients who previously had negative sextant biopsy
results and persistent indications for repeat biopsy. Interestingly, 34% of patients were found to have
cancer with this technique . They did not specify in which locations cancer was ultimately
detected within the prostate gland. This result compares to 38.4% of patients who had previously
undergone sextant biopsy who were found to have prostate cancer on repeat biopsy using the 5-region
technique . Therefore, this approach appears to have only limited advantages in situations
were initial approach is sextant biopsy.
Saturation biopsies are also now increasingly utilized for patients with an initial biopsy diagnosis
of microfocal adenocarcinoma of ≤6, who are considering active surveillance treatment option. This
management option remains viable if there is no high grade component. Interestingly, in a study
performed by Boccon et al, 68% of patients with microfocal Gleason 6 prostate cancer at initial extended
biopsy were upgraded to a clinically significant cancer at repeat saturation biopsy suggesting that even
contemporary extended biopsy practice may not be sufficient to detect all cancers, specifically located
3) The role of transition zone biopsies
Although approximately 20% of prostate cancers originate in transition zone (anterior prostate),
isolated transition zone tumors detected on prostate biopsy are uncommon. The addition of transition
zone biopsies to the initial biopsy strategy increases detection rates by only 1.8% to 4.3%, and there
are few data to support the recommendation for routine transition zone sampling
However, in men undergoing repeat biopsy the yield of malignancy from the transition zone is higher,
ranging from 10% to 13%
Thus, the transition zone biopsies may be indicated in
patients in whom initial biopsies fail to reveal cancer but PSA continues to increase.
In conclusion, there is clearly a trend toward extended biopsy approach to improve the detection of
cancer. Ten to 12-core schemes is optimal in majority of initial and repeat biopsy patients. This
biopsy schemes are heavily weighted towards the lateral aspect and the apex of the prostate to maximize
peripheral zone sampling. The use of "saturation" biopsy appears to be limited in subset of patients
with high index of clinical suspicion in which previous attempts, particularly sextant approach are not
diagnostic. Most of the studies conclude that cancers detected by such approach are clinically
significant, though there is trend for detecting them at low volume and at earlier stage.
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