Revisiting extraprostatic extension based on invasion depth and number for new algorithm for substaging of pT3a prostate cancer

Abstract

Extraprostatic extension (EPE) is a factor in determining pT3a stage in prostate cancer. However, the only distinction in EPE is whether it is focal or non-focal, causing diagnostic and prognostic ambiguity. We substaged pT3a malignancies using classification of EPE to improve personalized prognostication. We evaluated 465 radical prostatectomy specimens with a digital image analyzer by measuring the number, radial distance and two-dimensional square area of the EPE. The most significant cut-off value was proposed as an algorithm for the pT3a substaging system to predict biochemical recurrence (BCR). A combination of the radial distance and the number of EPEs predicted BCR the most effectively. The optimal cut-off criteria were 0.75 mm and 2 mm in radial distance and multifocal EPE (hazard ratio: 2.526, C-index 0.656). The pT3a was subdivided into pT3a1, < 0.75 mm and any number of EPEs; pT3a2, 0.75-2 mm and one EPE; and pT3a3, > 2 mm and any number of EPEs or 0.75-2 mm and ≥ 2 EPEs. This combined tier was highly significant in the prediction of BCR-free survival. The combination of radial distance and number of EPEs could be used to subdivide pT3a prostate cancer and may aid in the prediction of BCR.

Figure 1

Gleason grade and extraprostatic extension (EPE). (A) Gleason patterns in the areas of EPE paralleled the dominant tumor pattern, usually Gleason patterns 4 and 5. (B) A few cancer cells scattered around the nerve outside of the capsule were often encountered and can indicate Gleason pattern 5. (C) In a few cases of PGG2 and 3, EPEs were scored as Gleason Grade 3, whether alone or more commonly mixed with Grade 4.

Figure 2

Kaplan-Meyer survival analysis according pT3a substage and the combination of pT3a substage and circumferential margin (CM) status. (A) The biochemical recurrence (BCR)-free survival was significantly different among pT3a subgroups (P < 0.001). (B) No significant differences were identified in OS (P = 0.145). (C) After the combination of pT3a substage and CM status, significant differences were identified among 3 subgroups (P < 0.001). (D) pT3a2/3 + subgroup showed longer OS than other subgroups (P = 0.001).

Figure 3

Schematic diagram of various cases of EPE. In general, EPE erupts from the origin of the tumor nodule. In cases of multifocal tumor nodules, which are frequently observed, multiple EPE foci can be present. When only radial distance is measured, the “A” type could be an EPE index because it is the longest in radial distance. However, in comparison with 2D areas that include circumferential length, the “C” type can be an EPE index. Another dilemma is whether EPE is associated with circumferential margin involvement. The combination of “C” type in 2D or “D” type in radial distance could be a more useful EPE index.

Figure 4

(A) An example of a pT2 case. The tumor showed definite protrusion beyond the prostate proper at the level of thick vasculature. However, fat pads were not apparently involved. In this case, we suggest a T2 classification. Although such cases are often encountered, they should not be dealt with as T3 cases. (B) The presence of tumor cells in anterior muscle bundles without neurovascular bundles causes controversy in the evaluation of EPE. Most accepted guidelines define EPEs as extending beyond the contour of the proper tissue. (C) EPE showed extensively broad-based sessile extensions of tumor beyond the capsule and fat pad.