A risk grouping algorithm for predicting factors of persistently elevated prostate‐specific antigen in patients following robot‐assisted radical prostatectomy

Abstract

Objective: After radical prostatectomy, prostate-specific antigen(PSA) value measuring ≥0.1 ng/mL is defined as persistent PSA(pPSA) and in many studies, it was found to be associated with aggressive disease and poor prognosis. Our aim in this study is to point out the pathological and clinical factors affecting pPSA among the patients who underwent robot-assisted radical prostatectomy(RARP) in an experienced academic centre and to make a useful risk grouping algorithm that can predict pPSA value based on operative data. Methods:We examined records of 1273 patients who underwent RARP retrospectively. Preoperative, operative and postoperative data were collected. Based on the PSA values (ng/mL) measured after 4-to-8 weeks of RARP, patients were divided into two groups as pPSA group (Group1)(n = 97) with PSA values ≥0.1 ng/mL and undetectable PSA group (Group2)(n = 778) with PSA values <0.1 ng/mL. Later on, Group1 was further divided into Group1a (PSA:0.1-0.2 ng/mL) and Group 1b (PSA≥0.2 ng/ mL) to evaluate biochemical recurrence(BCR).Results: Multivariate logistic regression analyses of the collected data revealed that preoperative PSA≥20 ng/mL, operation time, a postoperative international society of urological pathology (ISUP) grade of ≥4, pT 3-4 and pN were independently associated with pPSA. Based on these results, a risk grouping algorithm predicting pPSA was developed. By looking at the risk grouping algorithm pPSA was found in 98.9% of the cases with a preoperative PSA value of ≥20 ng/mL, an operation time of 150 min, a postoperative ISUP grade of 4-5, a positive lymphovascular invasion (LVI) status, pT3-T4, and pN+; while pPSA was found in 25.5% of the cases with a preoperative PSA value of <20 ng/mL, an operation time of 100 min, a postoperative ISUP grade of <4-5, a negative LVI status, pT<3-4 and pN-. The estimated BCR-free survival time was 16.3 months in Group 1a and 57.0 months in Group2 (P < .001). Adjuvant treatment ratio was 64.9% in Group1 and 7.1% in Group2 (P < .001). Conclusion:For the patients who underwent RARP, factors associated with aggressive disease can predict the PSA persistence. To plan our treatment modalities accurately, an applicable risk grouping algorithm in daily practice would be useful. How to cite this article: Micoogullari U, Cakici MC, Kisa E, et al. A risk grouping algorithm for predicting factors of persistently elevated prostate-specific antigen in patients following robot-assisted radical prostatectomy. Int J Clin

Clinicopathological and oncological significance of persistent prostate-specific antigen after radical prostatectomy: A systematic review and meta-analysis

“…Finally, a total of 32 studies published from 1990 to 2021 were included in the current study ( Table 1 ). Of these 32 studies, 11 included 26 719 patients from cohorts with consecutive patients [ [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , 35 , 36 ] and the remaining 21 comprised 24 177 patients from cohorts with specific restrictions such as high-risk PCa, LNI, persistent PSA only, or receipt of SRT or ART treatment [ [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , 30 , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] ]. The majority of the studies with consecutive patient cohort was of high quality with seven or more stars according to Newcastle-Ottawa Scale assessment ( Table 1 ).…”

“…Given the heterogeneity of cases with different specific restrictions, we only conducted the meta-analysis based on the studies from cohorts with consecutive patients. All 11 studies with consecutive patient cohort provided the data on comparing clinicopathological characteristics between patients with undetectable and persistent PSA, and were suitable for OR meta-analyses ( Table 2 ) [ [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , 35 , 36 ]. Furthermore, nine out of the 11 studies contained information on oncological outcomes ( Table 3 ) [ 8 , 10 , 11 , [13] , [14] , [15] , [16] , 35 , 36 ].…”

“… Reference Year Group Period Total/persistent ( n ) RP cohort Persist cutoff (ng/mL) Persistent rate (%) BCR (ng/mL) F/U (M) NOS Clinical significance of persistent PSA after RP Micoogullari et al. [ 8 ] 2021 Turkey 2009–2017 875/97 Consecutive ≥0.1 at 6–8 weeks 11.1 Two consecutive PSA≥0.2 18–24 9 -0.1–0.2 ng/mL associated with aggressive disease and BCR in UV a Milonas et al. [ 9 ] 2021 Lithuania 2001–2019 1225/246 Consecutive ≥0.1 at 4–8 weeks 20.1 Two consecutive PSA>0.2 103 7 -Worse outcomes in high risk, worse BCR in intermedium in MV a Preisser et al.…”

“… Reference Log-rank test (K-M analysis), p -value Univariate HR (95% CI), p -value Multivariate HR (95% CI), p -value Covariate Micoogullari et al. [ 8 ] BCR p <0.001 (persistent worse) NA NA NA Preisser et al. [ 10 ] Mets p <0.001 (persistent worse) NA 3.59 (2.83–4.57), p <0.001 Year/age/pT/GG/pN1 Cancer-specific death p <0.001 (persistent worse) NA 3.15 (1.92–5.18), p <0.001 Year/pT/GG/PSM All-cause death p <0.001 (persistent worse) NA 1.86 (1.41–2.45), p <0.001 Age/pT/GG/PSM/CCI Spratt et al.…”

“…PSA of more than or equal to 0.1 ng/mL within 6 weeks after RP has been commonly used as the cutoff value to define persistent PSA in most of the prior studies [ [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] ]. The mechanism of persistent PSA has not been fully explored, and the potential explanations for persistent PSA were proposed to include residual benign prostate tissue, residual cancer burden from PSM, lymph node involvement (LNI), or occult micro-metastatic disease [ 29 ].…”