Incidence of adenocarcinoma in the transitional zone of the prostate in a public institution. Cochabamba, Bolivia

Incidencia de adenocarcinoma en zona transicional de próstata en institución pública. Cochabamba, Bolivia

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McNeal?s contribution of a zonal model allowed the division of the glandular prostate into four zones: the peripheral zone (70%), central zone (25%), transition zone and periurethral glandular region ¹.

The Peripheral Zone (PZ) has been considered the predominant location for the origin of prostate cancer 80% ^{2, 3}and the proximity of this zone to the rectal surface facilitates the diagnosis of PZ cancers by digital rectal examination (DRE) and transrectal needle biopsy ². On the other hand, malignant prostate neoplasms arising from the Transitional Zone (TZ) ¹; account for 20-25% of cases ⁴.

Most TZ cancers are located in the mid and apical prostate and due to their location, they are not palpable and are less frequently detected by standard biopsy schemes; consequently, they are larger when diagnosed compared to PZ cancers ⁵, their diagnosis is often incidental in transurethrally resected specimens.

PSA ₂ detection has improved prostate cancer (CA) detection ⁶, however, there is no specific normal or abnormal PSA concentration in the blood, and concentrations may vary over time, depending on the laboratory method, 4.0 ng/ml or less is considered the standard PSA value. The Gleason score is the most important predictor of prostate CA follow-up, metastasis and specific mortality. It is associated with an increased risk of biochemical recurrence and disease progression ⁴ ( Table 1).

Table 1
Risk of PCA in relation to low PSA values.
Dong F, Kattan MW, Steyerberg EW, Jones JS, Stephenson AJ, Schröder FH, et al. (2008) ⁶

Grignon and Sakr reported that TZ cancer has a distinctive histological appearance, consisting of well-differentiated glands covered by cells with clear cytoplasm and minimal nuclear atypia, including abnormal DNA content, which was much less frequent in TZ than in PZ cancers ³ .

TZ prostate cancers are associated with better clinical outcomes ⁴, because they show more favourable biological behaviour compared to those arising from PZ ⁵.

Therefore, the aim of this research is: to determine the incidence of Adenocarcinoma in the Transitional Zone of the Prostate and to identify the grade of Adenocarcinoma and precancerous stages of the same in patients with clinical BPH and PSA< 4ng/ml.

The universe consisted of patients treated for BPH in the Urology Service of the Hospital Clínico Viedma, a tertiary care centre in the city of Cochabamba, Bolivia.

The type of study was longitudinal and retrospective from January 2013 to December 2018. The study population included patients with IPSS -International Prostate Symptoms Score clinical picture based on answers concerning urinary symptoms and one question concerning quality of life ^{7, 8} ( Figure 1) ⁸ , rectal examination, vesico-prostatic abdominal ultrasound with measurement of residual urine). Inclusion criteria were simple prostatectomy, retropubic and/or transvesical prostatectomy or also called prostate adenectomy, PSA< 4ng/ml. Exclusion criteria: patients with PSA ?4ng/ml, operated radical prostatectomy and transurethral resection of the prostate (due to risk of loss of chips during examination in the pathology cassettes).

Figure 1 .
IPSS (International Prostate Sympthoms Score ) which is based on responses about urinary symptoms and asks about the quality of life.

The information was obtained from medical records filled out by urology specialists, for each patient taking into account benign prostatic hyperplasia, based on the Pathology Review System of the International Society of Urological Pathology (ISUP) ⁹ with or without atypia and neoplasms.The following criteria were used: prostate adenocarcinoma; prostate adenocarcinoma, ISUP 2016 modified Gleason System, within the Gleason range 6 to 10; with quantified total PSA of 0 to 4 ng/ml; high-grade PIN (intraepithelial neoplasia G2-G3) with prominent nucleolus; positive atypical small acini proliferation (ASAP); and extracapsular, lymphovascular and perineural invasion were also taken into account.

Data were collected and analysed using the Statistical Package for the Social Sciences (SPSS), descriptive statistics and absolute incidence formula.

The study identified 76 patients from the Viedma clinical hospital, who underwent prostate adenectomy during 2013 to 2018, which showed the following results ( Figure 2), 5 patients resulted with CA (adenocarcinoma 6.5%). In terms of invasion, they accounted for 80% with perineal invasion (5.3% of the 76 patients), 40% with lymphovascular invasion (2.6% of the 76 patients) and none with extravascular invasion ( Table 3).

Figure 2
Percentage of patients with benign prostatic hyperplasia (BPH), cancer (CA), atypia during 2013-2018 )

Table 3.
Patients with adenocarcinoma according to invasiveness

The 5 patients with adenocarcinoma represent a median age of 82 years, who are at risk of lethality during the next few years due to ISUP grade 3-5 and considering the invasion characteristics.

Regarding precancerous or atypical stages, there were 9 patients representing 10.5% ( Table 2), with high-grade PIN (Intraepithelial Neoplasia G2-G3) 2.6%, ASAP, 7.9%. Of these, 8 patients are older than 75 years who are at risk for cancer development during the next 10 years.

Tabla 2
Results of high-grade PIN patients, ASAP, adenocarcinomas in Gleason scale, according to age.

Table 4.
Indications for the surgical treatment of benign prostatic hyperplasia

Some controversy has arisen between TZ and PZ prostate cancer and about differences in biological behaviour compared to those arising in PZ. In many respects, patients with TZ and PZ cancer appear to be similar. However, we identified several important differences between TZ and PZ cancer that suggest differences in their biology. Despite many similarities in the clinicopathological features of these cancers, TZ cancers showed better clinical outcomes with respect to biochemical recurrence, local and distant metastasis, TZ cancers are diagnosed at larger cancer volumes and higher serum PSA levels ⁵. However, total PSA does not have normal values for prostate CA negativity ¹⁰, but values from 0 to 4 ng/ml were available, and the further away from zero, the higher the risk of prostate CA and intermediate-high risk prostate CA ¹¹. However, the significance of this investigation was to find high-risk prostate CA (3 patients with ISUP 5), presenting with total PSA less than ⁴.

Despite the clinical instruments and surgical indications ( Table 3)12 for the decision of surgery for presumed benign prostatic hyperplasia (BPH) ¹², there is a 6.5% incidence of adenocarcinoma in the Transitional Zone in the study conducted.

The role of immunohistochemistry is important and with it that of Ki67 protein as a prognostic marker, androgen receptor overexpression plays an important role in disease progression and correlates with high Ki67 expression and has been shown to be an independent prognostic factor in the biochemical recurrence-free period ¹³ and Matrix Metalloproteinases (MMPs) as markers of invasion ¹⁴.

In the study, there is a 10.5% incidence of presentation of atypical ASAP and PIN forms, which are more important precursors of prostatic carcinoma. High Grade PIN (HGPIN): tufts, micropapillary, cribriform and flat identifies patients at risk of malignancy ¹⁵, which according to the literature has a 40-50% risk of progression to prostate cancer (CAP), with progression to indeterminate Gleason grades and indeterminate time ¹⁶. As mentioned by Bostwick, most patients with PIN will develop carcinoma within 10 years ¹⁷. In the study 17.1% of patients are at risk of disease lethality. It can be assumed that patients older than 75 years at risk of cancer mortality were in optimal condition and probably had a life expectancy of more than 10 years when they underwent adenectomy and were at low to intermediate surgical risk and ASA II, so that they are at risk of cancer mortality in the next 10 years. Predicting the aggressiveness of PDA is critical for appropriate surveillance and early selection of adjuvant therapies. There are new advances that help in this type of prediction such as the advances of Rojas et al. who presented the genetic score as a novel tool for predicting indicators of aggressive CAP ¹⁸.

Although the difference in the consequences of PDA remains controversial, due to its cause by location and/or particular biology, tumour location was strongly associated with the risk of extracapsular extension, seminal vesicle invasion, lymphovascular invasion and lymph node metastasis after adjusting for Gleason score, high-grade disease volume and serum PSA ⁵. An advance in the understanding of PDA by location will mean improved diagnosis and follow-up of the disease and the creation of specific clinical guidelines for each of these identities. In conclusion, the 6.5% incidence of adenocarcinoma in the Transitional Zone of the prostate is not negligible, even more so given that 60% of patients are high risk, despite the fact that the patients presented with a presumed clinical picture of BPH and that most have a life expectancy of more than 10 years. It is therefore suggested that the patient be fully and thoroughly informed about: 1) The management of prostate tissue performed in the different modalities of surgical therapies. Close monitoring of PSA, especially when atypical forms are present. Even in patients operated on for presumed BPH, a follow-up plan should be established for the only instrument available: PSA, individualisation of adjuvant therapies, and immunohistochemistry for TZ with Ki-67, MMP-2 and MMP-9 antibodies should always be taken into account.

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