Currently, there is an interest in optimizing the management of patients diagnosed with advanced PCa. Although advanced PCa generally has an unfavorable prognosis, under this definition there are also neoplasms that have a favorable prognosis or can even be cured by current treatment strategies, including surgery. Today, researchers are making special efforts to identify patients who will benefit from surgical therapy. Numerous recent studies have analyzed the pathological parameters with unfavorable prognosis present on the radical prostatectomy specimen. Among them, the most important unfavorable prognostic factors are considered the presence of positive resection margins, extra-prostatic extension, seminal vesicles invasion and the presence of positive lymphadenopathy. The data from the literature, regarding prognostic significance of the clinical and biological parameters analyzed in our cohort of patients, are contradictory. Thus, while some authors have demonstrated the association of serum PSA level with tumor volume, pathological stage and tumor extension, other authors have not shown significant correlations (8, 9). Moreover, the PSA level was inversely correlated with the Gleason score. And in another study, the serum level of preoperative PSA > 20 ng/ml was statistically significantly correlated with lymph node invasion and vesicle invasion (10). Due to recent studies, radical prostatectomy for patients with preoperative PSA greater than 20 ng/ml is considered a viable option, demonstrating encouraging results in this group of patients. In our cohort of PCa patients, 44.8% of patients had preoperative PSA levels > 20 ng/ml. Pre-operative PSA values correlated positively with the presence of positive lymphadenopathy (r = 0.28, p = 0.04) and the presence of lymph node invasion in more than 2 lymph nodes observed at the anatomopathological examination (r = 0.34, p = 0.01), but it was not statistically significantly correlated with the other elements of unfavorable pathology. Also, the Gleason score compared to prostate biopsy is considered a significant predictor of pathological outcomes after radical prostatectomy, and in addition, may predict unfavorable postoperative evolution. In our study, 37.5% of patients had a preoperative Gleason score higher than 8. The preoperative Gleason score correlated positively with the pathological Gleason score (r = 0.55, p < 0.001) and moderately positively with the presence of lymph node invasion (r = 0.45, p = 0.04) and with the presence of seminal vesicle invasion (r = 0.46, p = 0.03) or with the presence of bilateral invasion at the level of seminal vesicles (r = 0.40, p = 0.04). The results of our study are consistent with other clinical studies on the importance of the Gleason score in predicting seminal vesicle invasion (10) or the presence of positive lymphadenopathy (11, 12).
Digital rectal examination (DRE) is used in the clinical examination of patients to determine the local tumor stage and is associated with the local extension of the disease (clinical T stage). DRE has also been associated with an increased risk of detecting forms of PCa with a Gleason score above 8 (13). Currently, DRE is used in combination with other parameters to improve the predictive power of tumor extension. In our study, the clinical T stage was positively correlated with the presence of extra-prostatic extension (r = 0.40, p = 0.02) and with the presence of a bilateral seminal vesicle invasion (r = 0.40, p = 0.02). Of all the clinical and biological parameters analyzed, only the clinical T stage ≥ cT3a was statistically associated with an unfavorable pathological prognosis (67.7% vs. 35.3%, p = 0.03). Moreover, in the multivariate analysis the presence of a clinical T stage ≥ cT3a was associated with a 4.73-fold increase in the risk of unfavorable pathological prognosis. The sensitivity and specificity of this parameter in our study was 68.74% and 65.71%, respectively. These data are consistent with the studies of Cooperberg MR et al. (2005) which included this parameter in their model of assessing the risk of recurrence of localized disease (14). Numerous clinical studies have analyzed the impact of age on the course of patients with PCa and have concluded that age is a significant predictor of biochemical relapse, tumor progression and specific mortality after RP (14 15). Some authors have shown that old age is significantly associated with the risk of biochemical relapse, tumor progression or distant metastases (15). In our group of patients, the mean age of patients was 65.1 years, and it correlated poorly with the preoperative Gleason score (r = 0.429, p = 0.002), the histopathological type of the tumor (r = 0.27, p = 0.05) and did not have statistical significance for the unfavorable pathological prognosis.
The Charlson Comorbidity Assessment Index (CCI) is the most commonly used oncology index and an important predictor of specific PCa mortality or mortality from other causes after RP. Albertsen et al. (2005) studied the probability of survival of 767 patients diagnosed with localized PCa and treated conservatively (observation or therapy of immediate or delayed androgenic deprivation). They found that for a Charlson score between 0 and 1, the overall survival rates at 15, 20, and 25 years were 26%, 15%, and 8%, respectively; at a Charlson score of > 1, overall survival rates at 15, 20, and 25 years were 11%, 6%, and 3%, respectively (16). Obviously, in this study, a higher Charlson score was correlated with a more unfavorable result (16). Although the Charlson score is probably the most commonly used comorbidity assessment index in the context of RP, in our study, CCI was not associated with unfavorable pathological aspects for patients with advanced PCa. However, we consider that this parameter, alone or in combination with the other parameters, will be useful in assessing the specific survival for the patients in our study.
The relationship between preoperative levels of endogenous sex hormones and RP outcomes is controversial in the literature. Some studies have reported a higher incidence of poorly differentiated tumors in patients with PCa and low serum testosterone levels (17). Three other retrospective studies have shown that low total testosterone is associated with unfavorable pathological features in RP specimens, but found no association with biochemical recurrence (18, 19). In addition, a clinical study from 2006, suggested that age-adjusted free testosterone correlates with poorly differentiated prostate tumors (20). Many circulating androgenic compounds, including testosterone, androstenedione (A), dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) can be converted to the metabolically active dihydrotestosterone (DHT). DHT, which is the most potent intraprostatic androgen, appears to play a significant role in initiating PCa. The inevitable occurrence of androgen-refractory PCa after hormone treatment suggests that androgens play a rather "permissive" role in tumor progression (20). Morote J et al. (2009), in a study of subjects with nonmetastatic PCa and independent androgens, pointed out that the lower the testosterone levels, the longer period of disease progression (21). In our study, the serum levels of testosterone, dihydrotestosterone, DHEA-S and androstenedione were not statistically significantly correlated with unfavorable prognosis at the histopathological examination of the biopsy specimen. In contrast, the serum level of dehydroepiandrostenedione was statistically significantly correlated with the presence of pathological extra-prostatic extension (r = 0.29, p = 0.05). The researchers tried to improve the characterization of high-risk patients and created different predictive models by combining preoperative variables to predict postoperative outcomes, such as prediction of extracapsular extension, seminal vesicle invasion, lymph node invasion (22). For example, Baccala Jr AA et al. (2010) or Gallina A et al. (2007), combined clinical T stage, serum PSA, biopsy Gleason score with age or percentage of tumor invasion on the biopsy fragment to predict seminal vesicle invasion (23, 24). Regarding the prediction of lymph node invasion, the most used models were established by Cagiannos I et al. (2003) and Briganti A et al (2006) (25, 26). Preoperative serum PSA, clinical T stage, biopsy Gleason score, and the institution where surgery was made, were predictors included in the Cagiannos nomogram (25), while PSA value, clinical T stage, biopsy Gleason score, and number of lymph nodes removed had were used in the Briganti nomogram (83% accuracy) to predict ganglion invasion (26). The combination of age > 60 years + preoperative PSA ≥ 20 ng/ml + preoperative Gleason score ≥ 8 was not statistically significantly associated in our study with unfavorable pathology parameters (p = 0.17).
In last years, markers of systemic inflammation and especially the neutrophils / lymphocytes rate have been studied in relation to the occurrence and prognosis of several types of neoplasms. Although the mechanisms of the immune response and its influence on neoplastic development are not fully known at present, many studies confirm a significant link between them (4). In a review published by Tang L. et al. (2016) it was shown that an increased NLR associated an increased risk of recurrence for localized and locally-advanced PCa, respectively a lower survival for patients with locally advanced PCa compared to those who had a low ratio before treatment (27). Moreover, a meta-analysis of 14 studies that included a total of 16,266 patients confirmed the prognostic role of NLR for a shorter survival and a shorter non-recurrence interval even for metastatic CRPC (mCRPC) (28). The results of our study confirm what has been previously published and support the premise that inflammation has a role in promoting metastasis, but does not influence the intrinsic characteristics of the tumor (Gleason score, tumor stage). NLR has a prognostic value for the presence of secondary lymph node determinations (p = 0.006). It is estimated that for these patients, overexpressed lymphadenectomy has the potential to improve oncological results.