Determinants of Long-term Survival of Patients With Locally Advanced Prostate Cancer

The Role of Extensive Pelvic Lymph Node Dissection

M Moschini; N Fossati; F Abdollah; G Gandaglia; V Cucchiara; P Dell'Oglio; S Luzzago; SF Shariat; F Dehò; A Salonia; F Montorsi; A Briganti


Prostate Cancer Prostatic Dis. 2016;19(1):63-67. 

In This Article

Materials and Methods

After institutional review board approval was obtained, data of 1586 pT3-pT4 PCa patients treated with RP and ePLND between 1987 and 2014 at one tertiary referral center were included in the study. Patients were staged preoperatively with pelvic/abdominal computerized tomography or abdominal ultrasound, bone scan and chest X-ray. Seven surgeons performed RP using a standardized retro pubic technique. Nerve sparing techniques was offered when oncologically safe according to preoperative patient characteristics according to the clinical judgment of the treating physicians. ePLND has been previously described[11] and consisted of excision of fibrofatty tissue along the external iliac vein, the distal limit being the deep circumflex vein and the femoral canal. Proximally, ePLND was performed up to and including the bifurcation of the common iliac artery. Furthermore, all fibrofatty tissue within the obturator fossa was removed to completely skeletonize the obturator nerve. The lateral limit consisted of the pelvic sidewall, and the medial dissection limit was defined by perivesical fat. In all the patients included in our cohort, LNs along the internal iliac vessels were dissected. In some cases, LNs located in the presacral and common iliac areas were also removed. LNs were processed at our center by experienced uro-pathologists, as previously reported.[12] Briefly, fat tissue containing LNs were fixed in 10% buffered formalin. The macroscopic specimen assessment was based on tactile and visual criteria. Large nodes (>2 cm) were sampled in multiple blocks. If no LNs were macroscopically detected, all fat tissue was processed. All blocks were embedded in paraffin, cut at 3 μm and stained with hematoxylin–eosin. Adjuvant therapy indications were based on the clinical judgment of each treating physician, according to patient and cancer characteristics. Additional treatments were considered as adjuvant therapies if administered within 3 months after surgery, regardless of postoperative PSA value. Adjuvant treatments consisted of radiation therapy (aRT) and/or androgen-deprivation therapy (adjuvant hormonal therapy). Specifically, 865 patients (54.5%) received aRT that was applied using the previously described technique.[13] Conversely, androgen-deprivation therapy consisted of maximal androgen blockade or luteinizing hormone-releasing hormone agonist alone or bicalutamide in monotherapy. Specifically, 547 patients (34.5%) received adjuvant hormonal therapy that was intended to be used lifelong. However, given the retrospective nature of the cohort, it is uncertain whether patients discontinued treatment. An informed consent was obtained from all subjects involved in the study.

Variable Definition

All patients included in this study had complete clinical and pathology data that consisted of age at surgery, preoperative PSA value, clinical stage (cT1 vs cT2 vs cT3), biopsy Gleason score (GS; ≤6 vs 7 vs vs pathological GS (≤6 vs 7 vs ≥8), surgical margin status (negative vs positive), LN invasion (no vs yes), number of RLNs and number of positive nodes.

Statistical Analyses

Descriptive statistics of categorical variables focused on frequencies and proportions. Means, medians and interquartile ranges (IQRs) were reported for continuously coded variables. Chi-square and Mann–Whitney tests were used to compare the statistical significance of differences in proportions and medians, respectively. Univariable and multivariable Cox regression analyses were used to test the relationship between the number of nodes removed and CSM rate, after adjusting for all available covariates. Estimated survival curves were plotted based on the multivariable model results. Survival curves were stratified according to the number of RLNs, using the points of maximum separation, as described by Harrell. Finally, predicted 10-year survival according to the number of RLNs was plotted for the entire cohort and after stratification according to GS and aRT status. Statistical analyses were performed using the R statistical package (R Foundation for Statistical Computing, Vienna, Austria) and SPSS v 20.0 (IBM, Armonk, NY, USA), considering a statistical significance at P<0.05.