Outcome of TRUS Biopsy with Limited Cores in Patients with PSA More Than 50 ng/dL: Can We Reduce the Number of Cores Without Affecting Outcomes?

Abstract

The aims of our study were to see outcomes of limited core biopsy and compare its outcomes with standard 12-core biopsy in patients with PSA more than 50 ng/dL. We did a retrospective analysis of 149 patients undergoing prostatic biopsy with PSA more than 50 ng/dL between January 2014 and December 2018. Out of 149 patients, 49 underwent limited core (2 to 6 cores) TRUS biopsy with no systemic 12-core biopsy. Other 100 patients underwent standard 12-core biopsy under TRUS guidance. Total of 149 patient’s records were analyzed and were included in the final analysis. There was no significant difference in demographics and prostate-specific antigen among the cohorts. All 49 patients in limited core TRUS biopsy had a positive biopsy with no need of re-biopsy. Fourteen out of 100 patients in TRUS biopsy had a negative biopsy. All 14 patients with negative biopsy had an average follow-up of 3.8 years with no conversion to positive biopsy. Patients with PSA more than 50 ng/dL and high clinical suspicion of prostate cancer can undergo limited core biopsy without systemic 12-core biopsy. In patients with no clinical evidence of prostate cancer, 12-core biopsy remains the gold standard for evaluation of prostate cancer.

Introduction

Prostate cancer (CaP) is the second most common cancer in men worldwide and is the sixth leading cause of cancer deaths in these men. It is expected that by 2030, globally, number of prostate cancer may grow to 1.7 million new cases resulting in the death of around 499,000 patients due to the growth and ageing of the global population [1]. Even with the widespread availability of PSA screening many patients still present with locally advanced disease or metastases in the developing world [2].

In our study, we did a retrospective analysis of patients undergoing biopsy for prostate cancer with PSA more than 50 ng/dL. The objective of our study to evaluate outcomes of a limited number of cores [2 to 6] in patients with suspicion of locally advanced disease and avoid a 12-core standard TRUS biopsy without compromising outcomes of initial diagnostic evaluation. The aim of our study was to provide clinical evidence in support of biopsy practice of taking limited core (2 to 6) commonaly followed by many surgeons in clinical practice. Moreover, increasing number of cores in biopsy may be associated with more discomfort and may increase the burden on healthcare providers. To avoid such scenario, biopsy should include an adequate number of cores to provide sufficient tissue for diagnosis without increasing discomfort with minimal risk of re-biopsy.

Methods

We did a retrospective analysis of 149 patients undergoing prostatic biopsy with PSA more than 50 ng/dL between January 2014 and December 2018. Any patient who underwent prostatic biopsy for elevated PSA more than 50 ng/dL (doubly checked at 2-week interval) with no previous history of any medications or intervention which might alter PSA levels were included in study. Patients who had a previous negative biopsy, history of pelvic radiation, previous use of 5-a reductase inhibitors, and patients with incomplete clinical details were excluded from the study. PSA measurement was done using electrochemiluminescence assay, and final available result before the biopsy was used for final analysis. PSA more than 50 ng/mL was selected as Patil et al. in 2017 reported biopsy positivity rate of 100% in Indian males in this subgroup [3].

Out of 149 patients, 49 underwent limited core TRUS biopsy (2 to 6 cores) with no systemic 12 core biopsy. Other 100 patients underwent standard 12 core biopsy under TRUS guidance. Difference in number of cores is based on different practice among two consultant of surgical unit. One unit has a policy of limited core biopsy (2 to 6 cores) for any patient who presented with elevated PSA more than 50 ng/mL while other unit preferred 12-core biopsy in all patients irrespective of PSA levels. Biopsy in both groups was done under transrectal ultrasound guidance using BK flex focus 800 (BK Medical, Mileparkan, Denmark) with an 18-gauge biopsy needle (Biopty, C. R. Bard, Covington, GA, USA). Patient characteristics were recorded and are shown in Table 1. All patients underwent procedure trans-rectally under antibiotic cover (tab ciprofloxacin and tinidazole combination twice a day for 5 days). The procedure was done as day care, and all patients were discharged from hospital after 4 h. As per hospital protocol, all patients reported to the surgeon the next morning and followed up after 10 to 14 days for discussion of biopsy result in person. The requirement of emergency visits and the need for hospital admission was noted by a review of the electronic database of our hospital. Pathological examination was done by a dedicated uro-pathologist in the same institution. All patients were followed up and in case of negative biopsy were offered saturation biopsy if PSA is persistently elevated. One out of 14 patients underwent saturation biopsy.

Table 1.

Patient characteristics

	Limited core biopsy	12-core biopsy	p value
Number of patients	n = 49	n = 100	0.119
Age (years)	74.82 ± 8.69	70.90 ± 7.95	0.007
PSA (ng/dL)	270.16 ± 327.99	267.04 ± 650.42	0.975
DRE suspicious for prostate cancer	49	94	0.824
Clinical stage T2 and above	49	96	0.844

Statistical analysis was done using IBM SPSS version 20.0 (SPSS Inc., Chicago, USA). For all the continuous variables, the results are given in mean ± SD, and for categorical variables as a percentage. To compare the mean difference of numerical variables between groups, independent two-sample t test was applied. To find out the association between two categorical variables, chi-square test was applied. A P value < 0.05 was considered as statistically significant. Ethical committee approval was obtained from the institutional ethical committee for the study.

Results

Total of 149 patients were available for final analysis. Forty-nine patients underwent limited core biopsy (2 to 6 cores) while 100 patients underwent standard 12-core TRUS biopsy. Demographic profile, clinical stage, DRE findings, and PSA levels were comparable in both groups (Table 1). All 49 patients with limited core had a positive biopsy. Eighty-six out of 100 patients in the TRUS biopsy group were found to have prostate cancer. Average core positivity in limited core biopsy group was 3.22 ± 1.699 (out of 3.59 ± 2.263 core taken per patient with an average core positivity rate of 89.96%). In standard 12-core group, average core positivity rate was 7.60 ± 4.190 for 11.12 ± 2.479 cores taken per patient (average core positivity rate of 68.64%) (Table 2). Difference in Gleason score in both groups was not clinically significant. In limited core group 9/49 patients had Gleason score 7 or less while 40 patients had Gleason score of 8 or more. In standard 12-core biopsy, 24 had Gleason score of 7 or less while 62 had Gleason score of 8 or more. There was no significant difference in complications in both groups (Table 3). Four patients in TRUS biopsy group with negative biopsies were followed up with serial PSA, and one patient out of 14 underwent saturation biopsy at 3-month follow-up which was negative. Average follow-up on these patients is 3.8 years with mean PSA of 5.4 ng/dL with no conversion to positive biopsy on follow-up.

Table 2.

Average number of cores and total cores

	Limited core biopsy	12-core biopsy	p value
Average number of positive cores	3.22 ± 1.699	7.60 ± 4.190	< 0.001
Average number of cores taken	3.59 ± 2.263	11.12 ± 2.479	< 0.001

Table 3.

Complications

Complications	Limited core biopsy	12-core biopsy
Fever 38.5 or higher	0	1
Rectal bleeding	0	0
Macroscopic hematuria	1/49(2.04%)	3/100 (3%)
Patients requiring anesthesia	0	0
Patient requiring hospitalization	0	0

Discussion

With the change in practice and widespread availability of PSA testing, number of patients presenting with elevated PSA is increasing. Still in developing countries, many patients present with locally advanced prostate cancer with very high PSA values. Counseling and discussion about biopsy and its complications play a major role in relieving anxiety and stress associated with elevated PSA.

We did a retrospective analysis of patients with PSA more than 50 ng/dL and studied outcomes of biopsy with limited cores vs. 12-core biopsy group. The aim of our study was to find out if we can replace 12-core biopsy with 4 to 6 core biopsy based on clinical or clinical/TRUS findings and find out the rate of re-biopsy in such patients.

From the initial description of sextant biopsy in 1989 by Hodge number of cores required for biopsy has undergone significant changes over time. All previous studies have focused on the number of cores for patients undergoing biopsy for PSA less than 10 ng/dL and have found increased cancer detection rate of 22 to 32% in 12 core biopsy group [4–7]. In addition Sextant biopsies have false negative rates in the range of 15–34% based on repeated biopsies [8].

In 2009, Chavan et al. published outcomes of TRUS biopsy in Indian males with evaluated PSA. They reported biopsy positivity rate of 54.9% (56/102) for patients who had elevated PSA more than 50 ng/dL [9]. Similarly in 2011, Shina et al. reported biopsy positivity rate of 52%(24/56) for patients who had elevated PSA more than 20 ng/dL [10].On the other hand Patil et al. in 2017 reported biopsy positivity rate of 100% (34/34) for PSA more than 50 ng/mL in Indian males [3]. In Asian males, Alvin et al. in 2015 reported biopsy positivity rate of 72.3% (125/173) for PSA more than 20 ng/dL [11] and Yong et al. in 2016 reported biopsy positivity rate of 59.1%(146/247), and 93.5%(87/93) for PSA 20.0 to 100.0, and ≥ 100.0 ng/mL, respectively [12].

As the recent data suggested very high positivity rate when PSA is more than 50 ng/dL, less number of cores should be equally effective in the diagnosis of prostate cancer with high PSA. With this assumption and clinical practice, followed by one unit of our department, we analyzed our data and found no difference in outcomes between limited core vs stranded 12-core biopsy.

Our study has a limitation of potential selection bias with small sample size and retrospective study design. However, in patients with high suspicion of prostate cancer, limited cores [4 to 6] may be equivalent to full 12-core biopsy, with potentially less complications and less discomfort for patients. A prospective study with a larger sample size may help us in overcoming above limitations in future.

Conclusion

In patients with high clinical suspicion of prostate cancer, a limited number of targeted cores are equivalent to standard 12 core TRUS biopsy. Addition of extra cores does not change the outcome of biopsy in the select group of patients. If there is high clinical suspicion based on clinical findings less number of the core may provide an adequate sample for diagnosis without affecting clinical decision making, 12-core biopsy remains standard of care in patients with evaluated PSA without clinical evidence of cancer.