Taking into consideration the increased undertaking of screening tests for serum prostate-specific antigen (PSA), it would be envisaged that the diagnosis of prostate cancer at an early clinical stage and small tumour-size had been appreciably increased over recent years and as a consequence, the volume of tumour within radical prostatectomy (RP) specimens had decreased in size. Pathological stage pT0 is referred to as no evidence of residual tumour within a radical prostatectomy (RP) specimen from a patient in whom biopsy-proven prostate carcinoma had been histologically confirmed as a diagnosis. This entity was given a terminology of the "vanishing cancer phenomenon" by Goldstein and associates. The pT0 stage of prostate cancer had been noted ensuing hormone therapy or prior transurethral resection of the prostate (TURP) for benign prostatic hyperplasia before the undertaking of RP. Even though much research had addressed these two scenarios of pT0 stage prostate cancer, patients that manifest with pT0 status in cases other than the aforementioned two scenarios occur on very rare occasions which had been iterated to be in between 0.2% and 0.8% of all prostate cancer patients). Only few studies had examined such patients. The clinical significance of pT0 staging has remained not to be clear. Nevertheless, many reports had documented that that pT0 stage patients do portend a highly satisfactory clinical outcome. pT0 at RP is extremely rare. Although most pT0 patients had tended to have low serum PSA levels, low clinical stage, low biopsy Gleasson Score (GS), and only one positive biopsy core, those with more aggressive characteristics could still harbour pT0 at RP. In order to prevent the undertaking of unnecessary treatment of such clinically insignificant cancers, it would be important to ascertain preoperative clinical and pathologic characteristics which might help the Urologists and oncologist to pre-operatively ascertain patients with a high probability of pT0 staging upon RP specimens. The ensuing article has discussed general overview aspects as well as miscellaneous narrations and discussions from some case reports, case series and studies related to the varnishing prostate cancer in order to provide recent educative material on the varnishing prostate cancer to all readers. 

It has been iterated that carcinoma of prostate gland (prostate cancer) is the commonest malignancy which afflicts males within the western world, and that adenocarcinoma of prostate gland had often tended to be treated by the undertaking of radical prostatectomy (RP). [1] It had furthermore been iterated that with regard to rare cases of primary adenocarcinoma of prostate gland, no demonstrable cancer had been found within the radical prostatectomy (RP) specimen upon thorough pathology examination despite previous pathology examination features which had confirmed positive biopsy of prostate features of adenocarcinoma of prostate gland. It had been iterated in a number of published documentations that the incidence of pT0 disease or “vanishing cancer” or the finding of no evidence of prostate cancer upon subsequent examination of radical prostatectomy specimens examined pursuant to treatment of the prostate cancer as treatment of curative intent is very low and that the prevalence rates had ranged from 0.2% to 0.8% [1] [2], [3], [4]  It has also been documented that varnishing prostate cancer had been associated with neoadjuvant hormonal therapy, but varnishing prostate cancer may also occur outside of this setting [1] [4]. The finding of no evidence of prostate cancer or absence of prostate cancer within a radical prostatectomy specimen might represent a challenging situation as an enigma to both, the patient and the Urologist. Despite the rarity of the varnishing prostate cancer, considering that occasional cases of the varnishing prostate had been reported on sporadic occasions, it is important for the Urologist to ascertain, factors that may emanate in or be associated with the finding of the varnishing prostate cancer or the future finding of no evidence of prostate cancer as well as what needs to be done under such scenarios. The ensuing article on the Varnishing prostate cancer has been divided into two parts: [A] Overview of the varnishing adenocarcinoma of prostate cancer and [B] Miscellaneous narrations and discussions related to some case reports, case series, and studies related to the varnishing acinar adenocarcinoma of prostate gland. 

Aim 

To review and update the literature on the varnishing adenocarcinoma of prostate gland. 

Methods

Internet data bases were searched including: Google; Google Scholar; Yahoo; and PUBMED. The search words that were used included: the varnishing prostate cancer; the varnishing acinar adenocarcinoma of prostate gland; no evidence of prostate cancer in radical prostatectomy specimens following a previous positive prostate cancer confirmation in a prior prostate biopsy specimen. Forty-one (41) references were identified which was used to write the ensuing article which has been divided into two parts: [A] Overview of the varnishing adenocarcinoma of prostate cancer and [B] Miscellaneous narrations and discussions related to some case reports, case series, and studies related to the varnishing acinar adenocarcinoma of prostate gland.

[A] Overview 

Definition / general statements [5]

• It has been iterated that first described in 1995, vanishing cancer is a terminology that indicates no evidence of residual tumour found within radical prostatectomy specimen despite pre-radical prostatectomy confirmation of prostate cancer tumour within needle biopsy of prostate specimen. [6] 
• It has been pointed out that sometimes, only high grade prostatic intraepithelial neoplasia (HGPIN) or atypical small acinar proliferation suspicious for but not diagnostic of cancer ASAPP has tended to be found in some cases of the varnishing prostate cancer [5]

Essential features

The essential features of acinar ductal adenocarcinoma of the prostate gland that is referred to as the varnishing prostate cancer had been summated as follows:[5]

• It has been iterated that the contemporary incidence of vanishing cancer is 0.2% of radical prostatectomy specimens and that it was higher a decade or two ago when prostatectomy was being undertaken for smaller / lower grade cancers of the prostate gland. 
• It has been stated that the incidence of the varnishing prostate cancer is higher within large prostates or in preoperatively treated ones
• It has been iterated that the resolution of dilemma of the varnishing prostate cancer does entail complete tissue submission of the prostate specimen, cancer specific immunohistochemistry stains, utilisation of second pathologist opinion, consideration of flipping blocks to other surface as well as it has been iterated that some residual cancers simply cannot be detected after the above efforts had been undertaken

Epidemiology

The epidemiology of the varnishing prostate cancer acinar adenocarcinoma of the prostate gland has been summated as follows: [5]

• It has been iterated that the most recent incidence of varnishing prostate cancer at prostatectomy was 0.2% of 160,532 with clinically localized cancer based upon Surveillance, Epidemiology and End Results (SEER) database (2004 - 2015) [7] 
• It has been iterated that the aforementioned recent incidence of varnishing prostate cancer is lower than the incidence of vanishing cancer of 0.6% up to 4.9% of prostatectomy specimens a decade earlier, [8] [9] [10] [11] [12] 
• Variation in rate is probably due to the institution and time of the study; however, the recent decrease may reflect upward stage and grade migration at prostatectomy, due to increased acceptance of active surveillance for low grade cancer [13] 
• Predictors of vanishing cancer included a prostate weight ≥ 60 g or patients with prostate specific antigen (PSA) < 20>

Aetiology [5]

• Most often, the phenomenon is attributed to the fact that routine histologic sections cannot evaluate every cubic millimetre of prostate volume, so small cancer foci remain in the paraffin block [5]
• Rarely, prostate cancer may have been ablated by the biopsy or transurethral resection procedure [14] 
• Currently, more patients are receiving preoperative androgen deprivation, such as enzalutamide, that shrinks the cancer [15] 
• It had also been proposed that a minute cancer focus at the edge of the prostate may be inadvertently left behind in the overzealous attempt to perform a nerve sparing procedure [11] 

Diagnosis [5]

• Diagnostic resolution should include these steps in the following order: [7] 
• If the prostatectomy tissue has been partially submitted, complete submission should be pursued
• Get a second pathologist, particularly a urologic pathologist, to reread the resection slides
• Review the biopsy that was diagnostic of cancer, if slides are available
• Immunohistochemistry stains 
• Flip tissue in some or all of the paraffin blocks and have the opposite surfaces of the tissues cut
• DNA identity analysis can be performed if specimen switching is suspected 

Laboratory [5]

• Vanishing cancer patients typically have lower serum PSA [7] 

Gross description [5] 

• Larger prostates with an average size of 74 g are more likely to exhibit no residual tumour [10] 
  • P504S racemase is positive in cancer; get immunohistochemistry stains on deeper levels, on areas initially suspicious for cancer 

Positive stains [5]

• Negative stains [5]
• p63 or CK903 negative in cancer
• Molecular / cytogenetics description [5]
• Microsatellite analysis can be performed on the prostatectomy and biopsy specimens to confirm specimen identity; this very rarely shows a specimen switch (1 in 10 cases of vanishing cancer was attributed to specimen mix-up) [2] 
• This is particularly indicated if there is high grade or high-volume cancer on the biopsy [2]
• Differential diagnosis [5]
• Biopsy specimen switch: [5]
• Specimen mix-up with another patient must be excluded if the biopsy showed high grade or high-volume cancer and no cancer is seen in the resection
• Molecular analysis can be performed [2]
• Biopsy false positive: [5] 
• Correct diagnosis of cancer on the prior biopsy should be confirmed
• Immunohistochemistry stains (AMACR+ / p63, HMCK-) can be used if not previously performed

[B] Miscellaneous Narrations and Discussions from Some Case Reports, Case Series and Studies Related to The Varnishing Prostate Cancer 

Goldstein et al. [6] stated the following: 

• Early detection efforts do identify prostate cancer at lower clinical and pathology stages, often resulting in smaller volumes of tumour within radical prostatectomy specimens. 
• In some cases, complete sampling of the radical prostatectomy specimen for biopsy-proven adenocarcinoma does demonstrate minimal or no residual cancer. 

Goldstein et al. [6] evaluated the clinical and pathology examination findings in 13 such cases in an effort to document this finding, which they had referred to as the "vanishing cancer phenomenon." Goldstein et al. [6] reported that the mean number of prostate-slides they had examined per case was 79 and the number of prostate-slides they had examined had ranged from 34 slides to 248. Goldstein et al. [6] summarised their results as follows: 

• Carcinoma was absent in two cases, present in a single focus in eight cases, and present in two foci in three cases. 
• The mean cancer volume in the 10 cases with residual tumour was 0.019 cc and the cancer volume had ranged between 0.003 cc and 0.038); the largest single dimension of any tumour focus was 3 mm. 
• All cancers were upon examination found to be well-differentiated or moderately -differentiated within the biopsy specimen and prostatectomy specimen. 
• Their results had indicated that in some cases cancer might be extremely difficult or impossible to find or identify within the prostatectomy specimen despite exhaustive sampling. 
• The incidence of this "vanishing cancer phenomenon" was probably increasing because more low-stage cancers were being treated by the treatment option of prostatectomy. 
• The inability to identify cancer in a prostate gland which had been removed for needle biopsy-proven carcinoma might not indicate technical failure.
• Knipper et al. [7] stated that the incidence of pT0 prostate cancer (CaP) at radical prostatectomy (RP) is very rare. Knipper et al. [7] stated that they had undertaken the first population-based analysis of pT0 CaP at radical prostatectomy (RP). With regard to the methods of their study, Knipper et al. [7] reported that within the Surveillance, Epidemiology, and End Results database (2004-2015), they had tested for clinical and pathological characteristics according to pT0 versus. non-pT0 CaP and included a multivariable logistic regression model. Knipper et al. [7] summarised the results as follows: 
• pT0 was identified in 358 (0.2%) out of 160,532 clinically localized radical prostatectomy (RP patients). 
• The majority of pT0 patients had manifested with serum initial prostate-specific antigen (PSA) levels <10>
• Nevertheless, pT0 was identified in 13 (3.6%) patients with serum PSA level ≥20 ng/ml, in 69 (19.3%) patients with biopsy GS ≥7 and in 78 (21.8%) patients with ≥cT2 disease. 
• In a subset of patients with available number of biopsy cores, pT0 was identified in 34 (33.3%) patients with ≥2 positive biopsy cores. 
• Age, race, marital status, hospital region, population density, serum PSA level, as well as number of biopsy cores did not discriminate between pT0 and non-pT0 cases. 
• Analyses according to annual rates (2004-2015) of pT0 had not varied between the years (0.2%-1.6%, estimated annual percent change: -1.6%, P = 0.3). Neither did the rates vary according to geographic region.

Knipper et al. [7] made the ensuing conclusions: 

• The finding of pT0 at RP is very rare. 
• Although, most pT0 patients had low serum PSA levels, low clinical stage, low biopsy Gleasson Score, and only one positive biopsy core, those who had more aggressive characteristics could still harbour pT0 at radical prostatectomy (RP).
• Korarac et al. [8] stated that: "Vanishing carcinoma phenomenon" (VC) had been defined as the finding of minute or no cancer within radical prostatectomy specimens after a positive biopsy of prostate cancer. Korarac et al. [8] discussed their experience with VC and recommended guidelines for its detection as follows.
• One thousand seven hundred forty-one radical prostatectomy specimens (2004-2009), which they had processed by whole-mount section procedure had yielded 21 (1.2%) cases with VC and 6 (0.34%) cases with minimal carcinoma (≤ 2 mm) within the radical prostatectomy specimen. 
• To find the eluding carcinoma in VC cases or more carcinoma in minimal carcinoma cases, the following was undertaken: 3 levels of all the paraffin blocks were obtained; if negative, the paraffin blocks were melted, the tissue was flipped, and 3 levels were prepared. The tumour bank frozen tissue was also processed for routine pathology examination.
• Korarac et al. [8] summarised the results as follows: 
• Three deeper levels within the radical prostatectomy specimen of 21 VC cases had failed to demonstrate malignancy; nevertheless; the flipping and recutting of the tissue had yielded a focus of carcinoma (1-5 mm) in 16 of 21 cases and in 3 of 16 cases in the saved frozen tissue. 
• In 1 of the 6 cases with minimal carcinoma, subsequent recuts of the flipped tissue had displayed carcinoma (2 foci of tumour, <1>

Korarac et al. [8] made the ensuing conclusions:

• In VC they had recommended the following: (a)Pathologists embed and process any remaining prostatic tissue including any saved fresh-frozen tissue; (b) Pathologists should obtain 3 levels of each paraffin block; if results are negative, then (c) pathologists should melt and flip the tissue and obtain 3 more levels. 
• Following the above guidelines, a hidden carcinoma might be detected in the majority of the cases of VC.
• Mazzucchelli et al. [9] stated the following: 
• The reported incidence of no residual prostate cancer (i.e. pathological stage pT0) on radical prostatectomy had ranged from 0.07% to 4.2%. 
• The incidence is higher pursuant to neoadjuvant endocrine treatment. 

Mazzucchelli et al. [9] undertook a study, to search for residual cancer on radical prostatectomy (RP) specimens when an initial sampling had failed to find the cancer in patients who had tumour positive biopsy. Mazzucchelli et al. [9] reported that they had reviewed their database of 1,328 consecutive patients whose biopsies and RP specimen were both examined at the Polytechnic University-United Hospitals of the Marche Region between March 1995 and June 2006. Mazzucchelli et al. [9] also reported that the radical prostatectomies were grossly completely sampled and examined with the whole mount technique. Mazzucchelli et al. [9] summated the results as follows: 

• They had identified eight patients (i.e. 0.6%; three untreated and five hormonally treated preoperatively, i.e. 0.3 and 0.8%, respectively, of the total number of RPs included in the study) with positive biopsy and with no residual cancer within the initial routine histological examination of the RP. The RP of this group of eight was subjected to additional sectioning and evaluation of the paraffin blocks of the prostatectomy, also after block-flipping, immunostaining with an antibody against CAM 5.2, p63, PSA, and alpha-methylacyl-CoA racemase, and DNA specimen identity analysis. There were no cases with a false positive biopsy diagnosis, and cancer was not overlooked or missed in the initial routine histopathology examination of any of the 8 pT0 RPs.
• A minute focus of cancer (the diameter was always below 2.0 mm) was found on the additional sections in five. In particular, cancer was identified after block-flipping in one of them. In an additional case, cancer was eventually discovered after immunohistochemistry staining tissue sections for cytokeratin CAM 5.2, for p63 and PSA. 
• In the remaining two cases (one untreated and the other hormonally treated), cancer was not identified or found (0.15% of the 1,328 RPs included in the study).
• Their review of the description of the macroscopic or gross appearance of the RP and of its slides had demonstrated or revealed that part of the peripheral zone corresponding to the site of the positive biopsy was missing, i.e. not removed from the patient at the time of the operation at least in one of the two. 
• DNA specimen analysis had confirmed the identity of the biopsy and prostatectomy within both. 
• An extensive search for residual cancer had reduced the number of pT0 RPs pursuant to a positive biopsy from 0.6 to 0.15%.

Mazzucchelli et al. [9] made the ensuing additional conclusions and recommendations: 

• It is recommended to have the needle biopsy reviewed, carefully look again at the radical prostatectomy, do deeper sections and then flip certain paraffin blocks.
• In addition, atypical foci should be stained for basal cell markers and often AMACR, especially in hormone-treated cases.
• If a block is missing part of the peripheral zone (capsular incision), this should be commented upon. 
• DNA analysis for tissue identity should be undertaken when the other steps had been taken without finding cancer.

Duffield et al. [10] iterated that radical prostatectomy (RP) specimens occasionally contain no carcinoma within the initial slides of an entirely submitted specimen, but no protocol had been established to assess for carcinoma in the remainder of the specimen. Duffield et al. [10] evaluated 34 cases with no carcinoma in the initial slide review of the entirely submitted RP over a 2-year interval out of 2200 RPs. Duffield et al. [10] reported that their sequential protocol for cases with no initial tumour included the following: (1) to review the biopsy; (2) to undertake immunohistochemistry staining on suspicious foci; (3) to perform levels on blocks with high-grade prostatic intraepithelial neoplasia; (4) to perform 3 levels on the posterior sextant and adjacent sextant region where cancer was identified on biopsy; and (5) to flip the blocks within these regions and to perform 3 additional levels. Duffield et al. [10] summarised the results as follows: 

• The mean age of the patients was 58.1 years and the ages of the patients had ranged between 41 years and 69 years, with a mean serum prostate-specific antigen level of 5.9 ng/mL (0.8 to 19 ng/mL). 
• Upon review, all of the biopsies had carcinoma with a Gleason score (GS) of 3+3=6. 
• The number of positive cores was 1 [n=29 (85%)], 2 (n=3), 3 (n=1), and 4 (n=1). 
• Fifty-nine percent (20/34) of the biopsies had immunohistochemistry (IHC) for basal cells and/or alpha-methylacyl CoA racemase.
• The radical prostatectomy specimens (RPs) on average had weighed73.6 g (36 to 155 g). 
• Out of the 34 cases with no initial cancer, cancer was found in 26 (76%), and 8 (24%) had no residual carcinoma despite extensive levelling in all cases and IHC in 1 case. 
• IHC was undertaken on 12 of the 34 RP cases. 
• Out of 26 RP cases with cancer, 22 had cancer on only 1 slide, and 4 had cancer on 2 slides. 
• All of the cancers in the radical prostatectomies were Gleasson Score (GS) 6, and the GS agreed with the corresponding biopsy in all cases. 
• In 83% (20/24) of cases that specified laterality within the biopsy, RP carcinoma was ipsilateral to carcinoma in the biopsy. 
• In 93% (14/15) of the cases that specified sextant site in the biopsy, the location of the carcinoma in the RP was in the same or the adjacent inferior-superior sextant site. 
• Out of the 29 cases that required levelling, in 7 cases cancer was found only after flipping the blocks and doing additional levels. 
• Out of the 8 cases with no cancer, all biopsies had only 1 positive core with 6/8 having <10>
• Duffield et al. [10] made the ensuing conclusions: 
• In about 1.5% of RP cases no tumour would be seen in the initially entirely submitted specimen. 
• A methodical limited targeted approach to the identification of cancer could identify cancer in 73% of the cases with no initial cancer, yet there will still be 0.4% of all RPs where cancer is not been identified or detected. 
• As cancer was seen in areas away from the biopsy site in some of their cases with minute tumour, levelling all the blocks might have identified cancer in some of the cases in which they found no tumour with their protocol.

Javali et al. [11] iterated the following: 

• Widespread serum PSA (prostate specific antigen) screening had resulted in stage migration of prostate cancer. 
• Smaller tumour volumes are being detected within radical prostatectomy specimens. 
• This had coincided with increasing reports about the 'vanishing cancer phenomenon.'
• In order to analyse the cases of robot assisted laparoscopic prostatectomy (RALP) within their institute in which the pre operative prostate biopsy was positive for adenocarcinoma but no tumour could be identified within the final histopathology, and they had reviewed the literature for possible reasons for such a phenomenon.
• With regard to the materials and methods of their study: Javali et al. [11] reported the ensuing: 
• They had identified nine patients out of a total of 184 cases of RALP in which the final histopathology had not correlated with the initial biopsy report. 
• The initial biopsy slides as well as the final histopathology slides were reviewed by a second pathologist. 
• The specimens were processed in entirety and additional sections were taken until no tissue was left.
• Javali et al. [11] summarised the results as follows: 
• Two patients had cancer diagnosed upon TURP (transurethral resection of prostate) chips, while the remaining patients had undergone TRUS biopsy for elevated serum PSA. 
• The final histopathology examination diagnosis was benign prostatic hyperplasia in two patients, chronic prostatitis in four patients, and acute florid prostatitis in one patient, granulomatous prostatitis with glandular-stromal hyperplasia in one patient and TCC (transitional cell carcinoma) of prostate in one patient.

Javali et al. [11] made the ensuing conclusions: 

• Majority of cases of pT0 are due to inability of routine histopathological analysis to identify minute tumour focus.
• Urologists need to be aware of this in view of the potential medico legal implications.
• Green et al. [12] retrospectively reviewed 1792 consecutive radical prostatectomies (RP) from 2003 to 2006 at a single institution in order to establish tumour volume reference values, to ascertain current trends in visually estimated prostate adenocarcinoma tumour volume, and to characterize cases with no residual cancer on RP. Green et al. [12] recorded tumour volumes and subsequently stratified them as very low, 0-1%; low, 1.1-10%; intermediate, 10.1-20%; high, 20.1-50%; and very high, >50%, with incidences of 11.7%, 52.1%, 21.5%, 13.2%, and 1.5%, respectively. Green et al. [12] summarised the results as follows: 
• The incidence of very low volume tumours had increased within the time period (p=0.04). 
• They had detected seminal vesicle involvement in 5.0% of cases and lymph node metastasis occurred in 1.4%. 
• Volume categories had statistically correlated with seminal vesicle invasion (p=0) and lymph nodes metastases (p=0). 
• They had identified eleven cases of no residual cancer (0.6%) with a non-statically significant increase during the study (p=0.07). 
• Green et al. [12] made the ensuing conclusions and recommendations: 
• The rising incidence of very low volume tumours should be considered by clinicians when discussing treatment options with patients. 
• A discrete tumour volume should be provided for RP specimens as it might be an important prognostic factor.

 Preisser et al. [13] stated the following: 

Two recent European studies had demonstrated an increasing proportion of non-organ-confined (NOC; pathologic stages T3-4) prostate cancer (PCa) in radical prostatectomy (RP) specimens. Preisser et al. [13] undertook a study, to ascertain if the trend for NOC and pT3-4 PCa is also evident among contemporary North American patients. With regard to the design, setting, and participants. Preisser et al. [13]: reported the following: Within the Surveillance, Epidemiology, and End Results database (2010-2014), they had identified 58 558 patients with clinically localized PCa which had been treated with RP. Preisser et al. [13] included only patients with clinical stage T1-2 and biopsy Gleason grade group (GGG) 1-3 prostate cancer (PCa). Preisser et al. [13] iterated the following:

• With regard to the Outcome measurements and statistical analysis, the annual trend analyses and multivariable logistic regression models had focused on the rate of NOC PCa, the rate of primary pathologic Gleason ≥4 PCa, and the rate of either NOC PCa and/or primary pathology Gleason ≥4 PCa. 
• Adjustment was made for clinical tumour characteristics (serum prostatic specific antigen [PSA] level, clinical stage of the tumour, and biopsy GGG).
• Preisser et al. [13] summarised the results and limitations as follows:
• The rate of NOC PCa had increased during the study period (18.7% versus 24.2%; p=0.002) and had remained significant after adjustment (16.9% versus 22.3%; p=0.001) 
• Similarly, the rate of pathology primary Gleason score ≥4 PCa had increased during the study period (16.8% versus 23.0%, p=0.001) and had remained significant after multivariable adjustment (10.8% versus 14.2%; p=0.002). 
• Furthermore, virtually the same findings were recorded when both endpoints were combined. 
• Their results were confirmed in multivariable logistic regression analyses in which year of diagnosis was modelled as a continuous variable or a categorical variable or when a cubic spline approach was used.
• Preisser et al. [13] made the ensuing conclusions as well as patient summary: 
• Rates of NOC PCa and primary Gleason ≥4 PCa had increased over time among contemporary North American patients who were treated with RP. 
• This finding might be related to better acceptance of active surveillance and watchful waiting by North American patients.
• In their report, they had looked at pathology outcomes for contemporary North American patients who had undergone treatment with radical prostatectomy for prostate cancer. 
• They found an increase in non-organ-confined and more aggressive prostate cancer.

Iczkowski et al. [15] stated that they had performed the first evaluation of the effects of the 5-alpha-reductase inhibitor class of drugs on cancer histopathologic features at radical prostatectomy in a placebo-controlled multi-centre trial. Iczkowski et al. [15] analysed prostatectomy slides in a blinded manner from 17 men who had been treated with dutasteride, an inhibitor of types 1 and 2 isoenzymes of 5-alpha-reductase, and 18 men who had been treated with placebo for 5 to 11 weeks before undergoing radical prostatectomy. The histopathology examination features of benign epithelium, high-grade prostatic intraepithelial neoplasia, and cancer were recorded, and the treatment effect was also scored. Digital imaging analysis was utilised to measure the stroma/epithelium ratio and epithelial height, as well as the nuclear area in cancer. Iczkowski et al. [15] summated the results as follows: 

• In benign epithelium, treatment had caused distinctive cytoarchitectural changes of atrophy and a decrease in the epithelial height (P = 0.053). 
• The peripheral zone demonstrated the most marked response to treatment. 
• Within cancer tissue, the tumour volume was significantly lower in the dutasteride-treated men than in the placebo-treated men (mean 15% versus 24%, respectively, P = 0.025), the percentage of atrophic epithelium was increased (P = 0.041), and the stroma/gland ratio was doubled (P = 0.046). 
• The treatment alteration effect score was doubled (P = 0.055) and had not correlated with any Gleason score changes.
• Iczkowski et al. [15] made the ensuing conclusions: 
• Pursuant to a short-term dutasteride treatment, benign epithelium had shown involution and epithelial shrinkage, and prostate cancer tissue had demonstrated a decrease in epithelium relative to stroma. 
• These findings had suggested that dutasteride induces significant phenotypic alterations in both the benign and the neoplastic prostate, supportive of a chemo-preventive or chemo-active role.

Montgomery et al. [16] stated the following:

• Prostate cancer is dependent upon androgen receptor (AR) activation. 
• Optimal AR antagonism might effectively cytoreduce local disease and suppress or eliminate micro-metastases. 
• They had evaluated neoadjuvant therapy prior to the undertaking of prostatectomy with the potent AR antagonist enzalutamide (enza) either alone or in combination with dutasteride (dut) and leuprolide (enza/dut/luteinizing hormone-releasing hormone analogues [LHRHa]).
• With regard to the experimental design and results of their study, Montgomery et al. [16], reported the following: 
• Forty-eight of 52 men with intermediate or high-risk localized prostate cancer had proceeded to undergo prostatectomy after neoadjuvant enzalutamide or enza/dut/LHRHa for 6 months. 
• They had assessed pathology assessment complete response (pCR), minimal residual disease (MRD; ≤3 mm maximum diameter of residual disease), residual cancer burden (RCB), and expression of PSA and serum and tissue androgen concentrations. 
• They had compared the proportion of patients with pCR in each treatment arm with a historical control rate of 5%, based on previous reports of flutamide with LHRHa.
• In the enzalutamide arm, none of the 25 patients achieved pCR or MRD. 
• Within the enza/dut/LHRHa arm, one of 23 patients (4.3%) achieved pCR and 3 of 23 (13.0%) achieved MRD. 
• The median RCB was higher in the enzalutamide arm than in the enza/dut/LHRHa arm (0.41 cm3 vs. 0.06 cm3, respectively). 
• Tissue testosterone and dihydrotestosterone levels correlated with RCB. 
• No adverse events leading to study drug discontinuation were reported.
• Montgomery et al. [16] made the ensuing conclusions: 
• Combination therapy with enza/dut/LHRHa had resulted in pCR and MRD rates comparable with historical controls. 
• Evidence of continued AR activity in residual tumour had indicated that AR signalling might contribute to survival. 
• Strategies to more effectively ablate AR activity are warranted in order to ascertain whether more substantial antitumor effects are observed. 

Kalampokis et al. [17] stated that following the undertaking of radical prostatectomy (RP), the absence of a demonstrable tumour on the specimen of a previously histologically proven malignancy is known as the pT0 stage. Kalampokis et al. [17 undertook a study to perform a narrative review of current literature in order to ascertain the frequency and oncology outcomes in patients with pT0 disease. Kalampokis et al. [17] undertook a narrative review of all available literature. Kalampokis et al. [17] summated the results as follows: 

• The incidence of pT0 had ranged between 0.07% and 1.3%. 
• Predictors of the pT0 stage were only a single biopsy core with low-grade cancer, a cancer length not exceeding 2 mm and a high prostate volume. 
• Biochemical recurrence had ranged between 0 and 11%. 
• Kalampokis et al.: [17] made the ensuing conclusions and recommendations:
• The absence of malignancy in the RP specimen despite a previous positive biopsy is a rare and unpredictable finding. 
• Even though the prognosis is considered to be excellent in majority of the cases, a continued close follow-up is warranted. 

Osunkoya et al. [17] iterated that one would expect cases with small foci of cancer at radical prostatectomy to be associated with correspondingly favourable (Gleason score < or>

• They had obtained one hundred fifty-one radical prostatectomy specimens with cancer involving 1 slide in 69 cases (45.7%), 2 slides in 61 cases (40.4%), and 3 slides in 21 cases (13.9%). 
• Predominantly transition zone cancer was identified in 1 patient (0.66%). 
• The mean age of the patients was 57.1 years and their ages had ranged between 41 years and 73 years. 
• Twenty-two patients that amounted to 14.6% of the patients had a suspicious digital rectal examination. 
• Mean serum prostate-specific antigen (PSA) and percentage free PSA were 5.2 ng/dL (0.3 to 16.7 ng/dL) and 15.5% (8% to 36%), respectively. 
• Out of 146 men, 127 men that amounted to 87% of men with available information had PSA density of less than 0.15. 
• The mean number of cores obtained was 12 (4 to 27 cores) and all were Gleason 3+3=6 cancers upon biopsy. 
• One hundred fourteen cases that amounted to 75.5% of the cases had 1 core positive, 28 cases (18.5%) 2 cores, and 9 cases (6%) had 3 or more cores positive. 
• One hundred forty-eight cases that amounted to 98% of the cases had cancer involving 50% or less of 1 core; 2 of these cases with greater than 50

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Acknowledgements to: The Korean Journal of Urology for granting permission for reproduction of figures and contents of their Journal article under copyright: Copyright © The Korean Urological Association, 2010

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