2.2 LENGUAJE DE LA MODA – VESTIDOS DE NOVIOS
2.2.2 TRAJE DEL NOVIO
Abstract
ObjectivesTo evaluate the prognostic role of the length of a positive surgical margin (+SM) for biochemical recurrence (BCR) after radical prostatectomy (RP) for prostate cancer.
Methods
Consecutive RP specimens (n=267) with +SM were analysed. All RP specimens were sectioned at 4-mm intervals and completely embedded. Data were analysed using Kaplan- Meier survival analysis and proportional hazards models.
Results
In 267 patients length of +SM ranged from 0.4 to 174.5 mm (median 11.2 mm) and correlated with preoperative PSA (p< 0.001), pathologic stage (p < 0.001), tumour volume (p = 0.001), number of +SM (p <0.001), Gleason grade at +SM (p < 0.001) and Gleason score (p = 0.015). Patients with detectable postoperative PSA levels (N=34) or adjuvant therapy (N=59) were excluded from for BCR-analysis. In the remaining 174 patients the 5-year risk of BCR was 29%; in patients with +SM ǂȱ ŗŖȱ ȱ ȱ ǁȱ ŗŖȱ ȱ ȱ ȱ ŘŗƖȱ ȱ řşƖǰȱ ¢ǯȱ ȱ ȱ¢ȱȱ ȱȱ ȱȱȱȱȱƸȱǻǂȱŗŖȱȱǯȱǁȱ
10 mm; HR 2.15; 95% CI 1.12-4.15; p = 0.022).
Conclusions
The length of +SM is an independent prognostic factor for BCR in patients with undetectable PSA after RP.
van Oort IM, Bruins HM, Kiemeney LA, Witjes JA, Hulsbergen-van de Kaa CA. The length of positive surgical margins correlates with biochemical recurrence after radical prostatectomy. Submitted
Introduction
The four most common characteristics used to predict progression of prostate cancer after radical prostatectomy (RP) are Gleason score, pathological stage, tumour volume and positive surgical margins (+SM)(11) The prevalence of +SM has been reported to range from 10%-48%(5). Clearly, it is the only prognostic factor that can be influenced by surgical technique. Most investigators agree that the presence of a +SM may adversely affect cancer control after RP (5, 8, 13, 18, 23). In a recent study by Eastham et al. the risk of progression after 10 years for patients with +SM is approximately 30-54 % depending on the pathological stage compared to 16-22 % for those with negative surgical margins(6). A multi-institutional study by Karakiewicz et al. showed a 3.7-fold higher risk of progression for patients with +SM(13). Others, however, disagree and state that it has only limited prognostic value for PSA relapse and local recurrence(21, 23).
To our knowledge until now, three studies have investigated the prognostic value of the length of positive surgical margins with contradicting results (4, 14, 17).
Therefore the purpose of this present study was to evaluate the correlation between the length of +SM and BCR after RP in a large cohort of 267 patients, with uniformly and completely processed specimens.
Materials and Methods
Between 1995 and 2005, 267 consecutive patients with +SM in the prostatectomy specimen were evaluated. This total group (N=267) was analysed for associations between the length of the +SM and different prognostic variables. Of these 267 patients, 34 never reached an undetectable PSA level post-operatively, indicating residual disease, and another 59 received adjuvant hormonal (N+ disease) or radiation treatment (T4 disease, amongst others). These 93 patients were excluded from the analysis of risk of BCR, leaving a group of 174 patients (analysis of BCR group).
All RP specimens were uniformly processed and entirely submitted for histological investigation, according to previously described protocols(12,20). Immediately after surgical resection specimens were fixed in 10% neutral-buffered formalin, using fine needle formalin injections and fixation overnight. Subsequently, the entire surface was marked with ink using three different colours (black for the posterior side, green and red for the right anterior and left anterior side, respectively), after which the entire prostate specimen was cut into serial transverse 4 mm thick slices, perpendicular to the dorsal-rectal surface and all slices were macroscopically photographed. The apex and base were sagittally sectioned to assess the caudal and cranial surgical margins. Seminal vesicles were amputated at their junction with the prostate and sectioned parallel to their junction and embedded in total. The remaining slices were subdivided into halves or quadrants to fit routine cassettes. After histological staining all specimens were evaluated by one expert urological pathologist (C.A.H.K.). Tumours were outlined on the microscopic slides and subsequently mapped on the macroscopic photographs to allow reconstruction of tumour extent and multifocality (fig. 1).
Figure 1. Schematical drawing on the macroscopic photographs of the radical prostatectomy specimen. Multifocal tumor was diagnosed, numbered 1-4. Positive resection margins are indicated. (GS = Gleason score of the entire tumor nodule; EPE =
of surgery, but retrospectively all tumours were re-staged according to the 2002 TNM staging criteria(10). Extraprostatic extension was defined as extension of adenocarcinoma in periprostatic adipose tissue or beyond the confines of the normal glandular prostate (15,20) and seminal vesicle invasion as invasion of the seminal vesicle (muscular) wall beyond the level of their junction with the prostate. Tumour volume was calculated for each tumour by measuring the largest tumour diameter and the diameter perpendicular to the largest diameter in all sections containing tumour. Section tumour surface area was calculated from these diameters by assuming elliptical tumour shape, was integrated over all sections and multiplied by the slice thickness for each slice in which the tumour was present. Surgical margins were only considered positive if cancer cells were in the inked margin. The sites of margin involvement were marked on the slides. All cases initially reported as +SM were re- evaluated for total linear length of involvement, number of sites and location of involvement, and highest Gleason grade pattern at the involved location (C.A.H.K., H.M.B). The linear length of positive margin was measured in mm at each involved site by using the diameter of the microscopic field after calibration with an ocular micrometer (Zeiss axioscope: 40 x objective = 0.6 mm; 20 x =1.2 mm; 10 x = 2.5 mm; 5 x = 5.0 mm; 2.5 x = 9.0 mm; fig. 2 and 3).
Figure 2. Positive resection margin at the apex (HEx100). The tumour is covered with green ink over an area with a diameter of one high power field of 40x objective (0.6 mm; represented by the circle).
For each site involving more than one slice, the measurements were summed. Sites were recorded separately if they were at least 4 mm apart from each other. The locations of the +SM were classified and recorded as apical, posterior, posterolateral, anterior, bladder neck and at the site of seminal vesicle. For each location the total linear length of involvement was summed.
Figure 3. Positive resection margin at dorsal site (HEx50). Tumour reaches in the inked surface over a large area (8 mm; slightly less than one low power field of 2.5x objective).