Relación de la verdad y la validez: el razonamiento sólido

PCa is the most commonly diagnosed cancer in men and a crucial factor for patient survival is the accurate grading of the tumour. It is vital that this occurs in a uniform manner to ensure an accurate prediction of the tumour behaviour and an optimal selection of treatment (Cheng, Liang, Montironi et al. 2012). Currently, there are two major staging systems applied in clinical practice, the pathological based Gleason scoring and the Tumour-Node-Metastasis (TNM) staging based on clinical parameters. Gleason scoring is based on the histological appearance of tumour material within the prostate, whereas the TNM staging is considered to be clinical staging based on multiple clinically assessed parameters (Dunn, Kazer 2011).

1.3.4.1 Gleason scoring

Gleason scoring was developed by Dr Donald F Gleason (Gleason 1966). A reason for its success and wide application was its successful validation in about 5000 patients. The system is based on the pathological inspection of prostatic tissue sections and the categorisation of carcinoma cells into histological patterns (Humphrey 2004). The system uses five grades, which are used to calculate a score based on the sum of the first and second most prominent patterns. The differentiation of cells decreases from stage one to stage five (Fig. 1.8). Grade one presents well differentiated growth of closely packed, round and uniform acini (Humphrey 2004), whereas grade 5 tissue does not present any glandular differentiation and has lost resemblance to healthy prostate tissue. Gleason scoring is an important tool for the prediction of outcome of PCa patients.

Currently there are some debates about the differences of Gleason 7, which can be generated through 4+3 and 3+4 presented morphologies within the tumour specimen. Studies have shown that disease outcome varies depending on the prominence of stage 4 tissue (Stark, Perner et al. 2009). A study comparing disease outcome in patients with both categories of Gleason 7 has shown a three-fold higher likelihood of lethal PCa in patients with 4+3 compared to 3+4 (Stark, Perner et al. 2009). A further study has also shown a higher risk of cancer related mortality in cases of 4+3 compared to 3+4 (Wright, Salinas et al. 2009).

25 Another debate is regarding the Gleason score 6 and whether or not it should be categorised as cancer. A change in its category could have serious implications on the patient’s treatment and disease outcome. Autopsies on men over 50 have frequently identified the presence of Gleason 6 PCa. On a histological basis, Gleason 6 PCa is fulfilling the histopathological requirements to be defined as PCa; however, some scientists argue that Gleason 6 cancer does not fulfil all 6 hallmarks of cancer (section 1.1.3), and should therefore be treated differently (Carter, Partin et al. 2012, Eggener, Badani et al. 2015). A study on more than 14 000 patients with a Gleason score of six and below, which underwent radical prostatectomy, has shown in only 22 cases an involvement of the lymph nodes (Ross, Kryvenko et al. 2012). This supports the idea that active surveillance offers a favourable option for patients with Gleason 6.

This image has been removed by the author for copyright reasons

Figure 1.8: Schematic representation of tissue differentiation in PCa across the 5 Gleason scores (PCEC, 2019). Increased Gleason scoring correlated with decreased tissue differentiation.

1.3.4.2 Tumour – Nodes – Metastasis (TNM) Staging

TNM staging (Tab. 1.1) is a pathological staging method for the characterisation of solid tumours and is used to describe the tumour and its current state in more detail. T stands for the primary tumour and its potential invasion into surrounding tissue. N describes lymph node involvement and M stands for metastasis and gives information regarding tumour spread to distant sites (Sobin, Gospodarowicz 2009). The involvement of lymph

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nodes is one of the most important prognostic factors and the aggressiveness of PCa is closely linked to the tumour volume (Cheng, Liang et al. 2012).

Table 1.1: Summary of the TNM classification system adapted from (Sobin, Gospodarowicz 2009)

T – primary tumour

TX Primary tumour cannot be assessed T0 No evidence of primary tumour T1

(T1a, T1b, T1c)

Tumour does not cause any sign of symptoms. Tumour cannot be detected though palpation or digital imaging. However, histopathological analysis can detect the presence of malignant cells.

T2

(T2a, T2b, T2c)

Tumour can be detected with DRE but is still confined within the prostate. Subcategories describe size and penetration of the tumour within the prostate capsule.

T3

(T3a and T3b)

Tumour extends outside the prostate capsule. Subcategories describe the extension into further detail.

T4 Tumour has invaded tissues outside the prostate and seminal vesicles and has spread to nearby organs, such as the bladder or lymph nodes.

N – Regional Lymph Nodes

NX Regional lymph nodes cannot be assessed. N0 No metastasis found in regional lymph nodes. N1 Metastasis found in regional lymph nodes.

M – Distant metastasis

M0 No distant metastasis present M1

(M1a, M1b, M1c)

Distant metastasis. Subtypes describe the location of the metastases.

Through the combination of the defined TNM stages, Gleason score and PSA levels, the tumour can be attributed to a certain stage and the stages range from I to IV (Cheng, Liang et al. 2012).

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1.3.4.3 D’Amico risk classification system

A further risk classification system is the D’Amico scoring. This system is designed to categorise patients into 3 distinct groups of risk for recurrence of PCa after radical prostatectomy through the combination of TNM stage, biopsy Gleason score, and the PSA level prior to surgery (Tab. 1.2) (D'amico, Whittington et al. 1998) (Tab. 1.2).

Table 1.2: D'Amico risk classification system to categorise patients for risk of prostate cancer recurrence after radical prostatectomy . Risk classification is based on Gleason score, TNM stage and PSA levels prior surgery. Adapted from: (D'amico, Whittington et al. 1998)

D’Amico Risk

Group Gleason Score TNM Stage

Pre-operative serum PSA (ng/ml) Low Risk ≤6 T1 or T2a <10

Intermediate Risk ≤6-7 T1 or T2a/b 10-20

High Risk ≤7 T1 or T2a/b/c >20

8-10 T1 or T2a/b/c Any PSA