Prostate cancer (CaP) is the most common malignancy in men and the second cause of cancer-related mortality after lung cancer (1). The diagnosis of CaP is mainly performed by digital rectal examination (DRE), serum prostate-spesific antigen (PSA) measurement and transperineal or transrectal ultrasound-guided biopsies. Prostate needle biopsy is one of the most common procedures performed in the common urological clinical practice; it is estimated that, in the U.S. alone, at least 800,000 prostate biopsies are performed annually (2).

Prostate biopsy has evolved over the years, starting from the technique described by Astraldi in 1937 (3) until the sextant prostate biopsy, described by Hodge et al in 1989 (4). Prostatic needle biopsy is currently considered the gold standard for the diagnosis of CaP and may be performed transrectally or transperineally, guided by ultrasound. The detection rates of these two techniques are comparable (5,6) and there is no final consensus regarding the optimal number of samples, although the British Prostate Testing for Cancer and Treatment Study has recommended 10 core biopsies (7), with antibiotic therapy, commonly quinolone, under local anesthesia.

The International Society of Urological Pathology (ISUP) Conference was held in March, 2005 in San Antonio, Texas (8), during which a panel of international expert uropathologists updated the Gleason grading, in order to increase the reproducibility and reliability of the evaluation of the biopsy specimens. A correct assignment of the Gleason score (GS) may be crucial in terms of prognostic and therapeutic management of CaP. Several studies have assessed the effect of the ISUP Conference on the concordance of Gleason pattern and the possible change of prognostic group.

Billis et al (9) evaluated 172 patients who underwent prostate needle biopsy and subsequent radical prostatectomy and described a significant effect of the ISUP Conference modifications on the evaluation of the Gleason patterns and the resulting change in prognostic group. Following re-evaluation of the specimens, an increase by 1 or even 2 score points was observed in 16.8 and 0.6% of the cases, respectively.

Furthermore, 26.7% of the ‘reassigned’ patients had a higher preoperative PSA level, a larger tumor, more frequent positive surgical margins and higher-stage pathological disease. After the re-evaluation, a higher number of patients was assigned to the prognostic group of GS 8–10, exhibiting, at follow-up, a shorter time to biochemical disease recurrence (log-rank P=0.011) (9).

In a more recent study that evaluated 590 biopsy specimens according to the classic and modified GS, the number of cores with 75–100% pattern 4 cancer was increased by 95% (10). Over the last few years, the bioptic GS has become increasingly important, since several patients may be offered therapeutic alternatives to radical prostatectomy, such as active surveillance, and prostate biopsy results represent a crucial point in the management of the disease.

Several studies have evaluated the correlation between bioptic and pathological GS, documenting a correlation ranging between 30 and 60%, particularly regarding low GS. The aim of this study was, therefore, to evaluate the association between bioptic and pathological GS in a series of patients undergoing prostate needle biopsy and subsequent radical prostatectomy and the possible prognostic factors of upgrading and upstaging.

The determination of the GS remains crucial in the evaluation of patients affected by CaP and in the management of this disease, which may range from an active surveillance protocol to radical prostatectomy and multimodal therapies. Several previous studies have analyzed the correlation between the biopsy evaluation and the results obtained from surgical specimens.

The comparisons between the results of the histological biopsy compared to the surgical specimen exhibited a correlation equal to ~50% (14–17). The results of the prostate biopsy and the surgical specimen may differ for several reasons, such as incorrect evaluation by the pathologist, sampling errors and the presence of borderline grading. Several studies demonstated that a higher number of cores, compared to the sextant biopsy, may lead to a lower percentage of upgrading.

Capitanio et al (18) evaluated a series of 301 patients with low-risk CaP according to the D’Amico criteria (19) (clinical stage T1c - T2a, PSA<10 ng/ml and biopsy GS 6) that underwent extended prostate biopsy (median number of cores, 18) and subsequent radical prostatectomy. The GS agreement between biopsies and surgical specimens was 47.5% (143 patients), while upgrading was recorded in 38.5% cases (116 patients), 31.9% of which (96 patients) presented with a significant upgrade to GS ≥7. In patients evaluated with 10–12 core biopsies, the upgrading was 47.9%, compared to 31.6 and 23.5% with 13–18 or >18 cores, respectively, with a statistically significant P-value, demonstrating that a larger sampling of the gland may avoid subsequent upgrading and may help in planning an appropriate treatment approach.

In our series, however, variables predictive of upgrading were not detected and the type of biopsy or the number of samples taken were not identified as predictors of upgrading. In 2012, Epstein et al (20) evaluated the largest series in the literature, with 7,643 patients, analysing the correlation between bioptic and definitive GS. Of the patients with GS 5–6, 36.3% underwent an upgrading and ~20% of the patients exhibited a tertiary Gleason pattern. In half of the remaining cases, there was an equal proportion of up- and downgrading. Half of the cases had matching GS 3+4=7 at biopsy and RP, with an approximately equal number of cases down- and upgraded at RP.

A bioptic GS 8 led to an almost equal distribution between RP GS 4+3=7, 8 and 9–10. A total of 58% of the cases had matching GS 9–10 at biopsy and RP. In addition, at the multivariate analysis, the authors reported that increasing age (P<0.0001), increasing serum prostate-specific antigen level (P<0.0001), decreasing RP weight (P<0.0001) and increasing maximum percentage cancer/core (P<0.0001) predicted the upgrading from a bioptic GS 5–6 to a higher one at RP (20). In our series, the presence of tertiary pattern was not assessed; therefore, we could not perform an evaluation regarding the presence and possibility of up- or downgrading.

In our study, with regards to GS 4-5-6, 44.2% of cases matched, while there was an upgrading in 54.4% of the cases. With pattern 3+4, there was a correlation between bioptic and definitive GS in 57.4% of the cases, downgrading in 6.4% of the cases and upgrading in 36.2%, a higher percentage when compared to the data presented by our colleagues. With GS 4+3, concordance was obtained in 35.3% of cases and a preponderance of upgrading (41.2%) compared to the downgrading (23.5%), an even higher percentage if compared to the data presented by Epstein et al (20). GS 8 was matched in 40% and GS 9–10 in 66.7% of the cases, almost overlapping with the data presented by our colleagues.

Epstein et al (20) also conducted a wide literature review, selecting only studies that evaluated series of patients with numerosity >100, documenting the presence of GS upgrading from 6 to 7 in 3,975 out of 11,472 cases (35%), with a mean percentage of 36.0% and a median of 35.5%, with results ranging from 14 to 51% (21–23). In our series, none of the analyzed variables was identified as an independent predictor of up- or downgrading, whereas a PSA level <4 ng/ml was found to be predictive of upstaging. In the literature, as in our study, age was not found to be a variable correlated with upgrading or upstaging, whereas age was found to be predictive in the study of Epstein et al (20), with a difference between the 2 groups of only 1.6 years.

PSA values, in contrast to our data, are often found to be predictive of upgrading, albeight with weak associations. According to our data, a preoperative PSA <4 ng/ml was found to be an independent predictor of upstaging; this highlights the questions regarding cancer as an incidental finding, which, even with low PSA levels, is found to be significant, as already suggested by Thompson et al (24). Moreover, in the literature, an increase in prostate volume was found to be less predictive of upgrading, while in the study of Epstein et al a decrease was documented in the upgrading ratio in prostate glands weighing >75 g.

Approximately half of the studies available in the literature documented an association between the percentage of cores invaded by cancer and upgrading; however, in this study, we did not consider this variable. The significance of the ability to predict a possible upgrading or upstaging of prostate biopsy lies with the risk of ‘falsely’ estimating a low GS, which may lead to the selection of a treatment not adequately aggressive, potentially putting the patient at risk of poor oncologic outcomes. For this reason, Serkin et al (25) retrospectively evaluated 2,884 patients who underwent radical prostatectomy, documenting an upgrading in 36.8% of patients with a bioptic GS 6. The authors of that study also demonstrated that the status of the surgical margins, capsule, seminal vesicles and lymph node involvement were more favorable in patients with a GS correlation between bioptic and surgical specimens (P<0.0001).

Moreover, patients with lower prostate volume had a higher PSA density and an increased risk of upgrading. The Kaplan-Meier curves suggested that patients with upgrading were at an increased risk of biochemical disease recurrence compared to patients with a correlation between the specimens (P<0.0001) and a higher risk to undergo salvage hormone therapy (P<0.0001).

Our study had several limitations, as follows: the design of the study was retrospective and over half of the biopsies were not performed in our Institution; we did not perform a centralized review of the specimens, with a variable number of biopsies and with the inability to evaluate, in some cases, the percentage of cores involved; we do not have an oncological follow-up of the patients and, therefore, we cannot correlate the biopsy results with the follow-up of the patients.

The upgrading and upstaging from prostate biopsy to radical prostatectomy is an important topic of discussion and may be of significant value at the clinical level, for treatment planning, as well as for the prediction of cancer outocomes. Therefore, new tools are required to predict upgrading and upstaging of our patients, in order to ensure better counseling for optimal treatment planning.