Prognostic variables associated with biochemical recurrence after radical prostatectomy for pT3b prostate cancer Текст научной статьи по специальности «Клиническая медицина»

JOURNAL OF CLINICAL MEDICINE OF KAZAKHSTAN

Озык, Макала / Оригинальная Статья / Original Article DOI:10.23950/1812-2892-JCMK-00543

Prognostic variables associated with biochemical recurrence after radical prostatectomy for pT3b prostate cancer

Ulanbek Zhanbyrbekuly, Jung Kwon Kim, Minyong Kang, Bumsik Tae, Ja Hyun Ku, Hyeon Hoe Kim, Chang Wook Jeong, Cheol Kwak

Abstract

Objectives: The objectives of the current study were to determine long-term biochemical recurrence rates stratified by adverse pathologic features and to identify predictive factors of biochemical recurrence rates following radical prostatectomy performed by either retropubic prostatectomy or robot-assisted laparoscopic prostatectomy from single tertiary center prostate cancer database.

Material and Methods: The Seoul National University Hospital prostate cancer database was queried for all patients treated with radical prostatectomy from 1999 to 2015. Among the 2680 patients who underwent radical prostatectomy, 331 patients with seminal vesicle invasion (pathologic T3bN0-1M0 stage) were identified. The primary endpoint was biochemical recurrence, defined as two consecutive postoperative prostate specific antigen values >0.2 ng/ml. Comparative analysis based on adverse pathologic characteristics and operation type was performed.

Results: Five and 10-year biochemical recurrence-free survival in the entire cohort was 59.0% and 42.9%. The Kaplan-Meier survival analysis demonstrated 5-year biochemical recurrence free survival rates differences in patients with different lymph node involvement (70.6% vs. 52.4%, log-rank, p=0.01). Variables including age, extracapsular extension, lymph node invasion, surgical margin, perineural invasion, multicentricity and Capra-S score were similar between the groups of patients who underwent either retropubic or robot-assisted laparoscopic radical prostatectomy. The mean prostate specific antigen level, seminal vesicle invasion laterality, tumor volume, and pathologic Gleason score were lower in the cohort of patients who underwent robot-assisted laparoscopic prostatectomy. No statistically significant differences were found in 5-year biochemical recurrence-free survival rates stratified by operation type (58.1% vs. 65%, log-rank, p=0.8), by Capra-S score (72.5% vs. 56.8%, log rank, p=0.1), or by surgical margin status (69.4% vs. 59.3%, log-rank, p=0.8). In univariate and multivariate Cox proportional regression analysis lymph node involvement (p=0.01) was found to be a statistically significant predictor of biochemical recurrence.

Conclusion: Patients with positive lymph node involvement have a poor prognosis. Capra-S score was unable to predict biochemical recurrence in patients with pathologic T3b stage prostate cancer. Robot-assisted laparoscopic prostatectomy is comparable to retropubic radical prostatectomy in terms of the biochemical progression of prostate cancer with seminal vesicle invasion.

Keywords: prostate cancer, seminal vesicle invasion, pathologic T3b stage, outcomes, radical prostatectomy

PT3B ЦУЬЩ АСТЫ ОБЫРЫНЫН, РАДИКАЛЬД1 ПРОСТАТЭКТОМИЯДАН КЕЙ1Н БИОХИМИЯЛЬЩ РЕЦИДИВПЕН БАЙЛАНЫСТЫ БОЛЖАМДЫЩ АЙНЫМАЛЫЛАР

Уланбек Жанбырбекулы, Джанг Квон Ким, Минйонг Канг, Бумсик Тэ, Джа Хьен Ку, Хьен Хо Ким, Чанг Вук Джонг, Чеоль Квак

Урологияльщ бeлiмi, Сеул ¥лттьщ Университетшщ Ауруханасы, Сеул, Корея

Т¥ЖЫРЫМДАМА

Максаттары: Осы зерттеудЫ максаттары, жогаргы децгейл1 орталыктын куык асты безшщ обыры мэлiметreр базасында ец нашар патологиялык керсеташтермен стратификацияланган биохимиялык рецидивтардыц житктИн аныктау менен ашык жэне робот-ассистенцияланган лапароскопиялык простатэктомиядан кейш биохимиялык рецидивтщ прогностикалык факторларын сэйкестендiру болган.

Эдютерк Сеул ¥лттык Университетiтiн ауруханасыныц куык асты обырыныц мэлiметтер базасында 1999-шы 2015-шл жылдар арасында радикалды простатэктомиямен емделген наукастардыц деректерi зерттелген. 2680 радикальд простатэктомия мен емделген наукастардыц Journal of Clinical Medicine of Kazakhstan: Volume 1, Number 47, Issue 2018

Department of Urology, Seoul National University Hospital, Seoul, Korea

© ®

This work is licensed under a Creative Commons Attribution 4.0 International License

Received: 2018-02-13 Accepted: 2018-03-05 UDC: 616.1

J Clin Med Kaz 2018;1(47):29-35

Corresponding Author: Ulanbek Zhanbyrbekuly, Department of Urology, Seoul National University Hospital, Seoul, Korea Email: ulanbek.amu@gmail.com

арасында, 331 обырынын тукымдык везикуларына басып KipyiMeH наукастар (патологиялык T3bN0-1M0 ауруыныц сатысымен) табылды. Бiрiншiлiк соцгы HYKте, отадан кейiн ПСА децгей >0.2 нг/мл eKi рет аныкталганнан кешн биохимиялык рецидив деп есептелетiн. Ец нашар патологиялык кврсeткiштeрмeн операция TYрiнe нeгiздeлгeн салыстырмалы талдау ЖYргiзiлдi.

Нэтижелерк Бес жэне 10 жылдык биохимиялык кайталанбайтын вмiр CYPУ барлык когортта 59,0% жэне 42,9% курады. Каплан-Мейердщ вмiр CYPУ талдауы лимфа TYЙiндeрiнe ауру тарауы жок жэне бар наукастарда 5-жылдык биохимиялык кайталанудан босату жылдамдшыныц айырмашылшын кврсeттi (70,6% 52,4%, log-rank, p=0,01). Жас, экстракапсулярлы тарау, лимфа тушндерЫе шабуылы, хирургиялык маржа, периневаральды шабуыл, мультиэнцентризм жэне Capra-S рeйтингiсi ретропубикалык немесе роботпен камтамасыз eтiлгeн лапароскопиялык радикалды простатэктомиямен ауыратын топтар арасында уксас болды. Роботпен камтамасыз еттген лапароскопиялык простатэктомиямен емделген наукастарда простата спецификалык антиген децгеш, тукымдык везикулага инвазияныц латералдмы, i^ квлeмi жэне патологиялык Глисон баллдары ашык эдiс простатэктомиямен емделген наукастардан твмен рек болган. Capra-S-тщ багалауы бойынша (72.5% vs. 56.8%, log rank, p=0.1) немесе хирургиялык шет бойынша (69.4% vs. 59.3%, log-rank, p=0.8) жэне операцияныц TYрi бойынша (58.1% vs. 65%, log-rank, p=0.8) 5-жылдык биохимиялык рецидивсыз вмiр CYPУ децгейлерЫде статистикалык м а ц ы з д ы айырмашылыктар табылмады. Унивариативтi жэне мультивариативтi Cox пропорционалды регрессиялык талдау кeзiндe лимфа

TYЙiндeрiнe катeрлi iсiк тарауы бар болуы (p = 0.01) биохимиялык кайталанудыц статистикалык мацызды предикторы болып табылды.

Корытынды: Лимфа TYЙiндeрiнe катeрлi гак тарауы бар наукастарда нашар болжам бар. Capra-S бойынша T3b простата катeрлi iсiгi бар наукастарда биохимиялык рецидив туралы болжау жасауга MYMкiндiк бeрмeйдi. Роботпен камтамасыз eтiлгeн лапароскопиялык простатэктомия мен ретропубикалык радикалды простатэктомиямен емделген простатикалык катeрлi iсiктeрдi тукымдык везикулярлык шабуылмен биохимиялык прогрессияга байланысты тец болып табылды.

Heri3ri сездер: куык асты безЫщ обыры, катeрлi iсiктiн тукымдык везикулага шабуылы, патологиялык T3b сатысы, ем нэтижeлeрi, радикальд простатэктомия

ПРОГНОСТИЧЕСКИЕ ФАКТОРЫ АССОЦИИРОВАННЫЕ С БИОХИМИЧЕСКИМ РЕЦИДИВОМ ПОСЛЕ РАДИКАЛЬНОЙ ПРОСТАТЭКТОМИИ У ПАЦИЕНТОВ С КАРЦИНОМОЙ ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ PT3B Уланбек Жанбырбекулы, Джанг Квон Ким, Минйонг Канг, Бумсик Тэ, Джа Хьен Ку, Хьен Хо Ким, Чанг Вук Джонг, Чеоль Квак

Урологическое отделение, Национальный Университетский Госпиталь Сеула, Сеул, Корея

РЕЗЮМЕ

Цели: Задачами данного исследования были определение частот биохимического рецидива стратифицированных по наличию наихудших патологических признаков и идентификация прогностических факторов биохимического рецидива после простатэктомии выполненной открытым или робот-ассистированным лапароскопическим способом по данным базы данных рака предстательной железы одного третичного центра.

Материалы и методы: В базе данных рака предстательной железы госпиталя Сеульского Национального Университета исследованы данные пациентов перенесших радикальную простатэктомию с 1999 по 2015 годы. Среди 2860 пациентов перенесших радикальную простатэктомию, у 331 была идентифицирована инвазия опухолевого процесса в семенные пузырьки (патологическая T3bN0-1M0 стадия заболевания). Первичной конечной точкой был биохимический рецидив, определенный как два последовательных повышения значений простата специфического антигена >0.2 ng/ml. Был выполнен сравнительный анализ основанный на наихудших патологических признаках и типе выполненной операции.

Результаты: Уровни 5 и 10- летней свободы от биохимического рецидива во всей когорте составили 59.0% и 42.9% соответственно. Анализ выживаемости по Каплану-Мейеру продемонстрировал разницу в уровнях 5 летней выживаемости без биохимического рецидива у пациентов без наличия вовлечения лимфатических узлов и с наличием (70.6% vs. 52.4%, log-rank, p=0.01). Такие переменные как возраст, экстракапсулярное распространение, поражение лимфатических узлов, хирургический край, периневральная инвазия, мультицентричность и число Capra-S не различались между группами пациентов перенесших позадилонную или робот-ассистированную лапароскопическую радикальную простатэктомию. Средние уровни ПСА, латеральность инвазии семенных пузырьков, объем опухоли, и число Глиссона при патологическом исследовании было ниже в когорте пациентов перенесших робот-ассистированную лапароскопическую простатэктомию. Не было выявлено статистически значимой разницы в уровнях 5 летней выживаемости у пациентов в зависимости от перенесенного типа операции (58.1% vs. 65%, log-rank, p=0.8), от числа Capra-S (72.5% vs. 56.8%, log rank, p=0.1), или от статуса хирургического края (69.4% vs. 59.3%, log-rank, p=0.8). В унивариативном и мультивариативном пропорциональном регрессионном анализе Кокса вовлечение лимфоузлов (p=0.01) было обнаружено как статистически достоверный предиктор биохимического рецидива.

Заключение: У пациентов с поражением лимфатических узлов отмечен более худший прогноз. Число Capra-S не обладало прогностической значимостью при оценке риска биохимического рецидива у пациентов с патологической T3b стадией рака предстательной железы. Робот-ассистированная лапароскопическая простатэктомия и позадилонная простатэктомия у пациентов с наличием инвазии в семенные пузырьки сопоставимы с друг другом в плане риска биохимического рецидива.

Ключевые слова: рак предстательной железы, инвазия в семенные пузырьки, патологическая T3b стадия, результаты, радикальная простатэктомия

Background

дениям о влиянии тиреоидных гормонов на синтез биогSeminal vesicle invasion (SVI) is found in almost 18% of patients who undergo radical prostatectomy, which is considered an established adverse pathologic feature and is strongly correlated with poor prognosis [1-4]. In contemporary literature, 5-year biochemical recurrence (BCR) rates in patients with SVI vary from 8% to 68% [5-7]. The objectives of our current study were to determine 5- and 10-year BCR rates stratified by adverse pathologic features and to identify predictive factors of BCR. As only a few centers have performed robot assisted laparoscopic prostatectomy (RALP) for more than 10 years at this time, there are only a few studies that have reported comparable oncologic outcomes after RALP and retropubic radical prostatectomy (RRP) in pT3b patients. The majority of these reports were single-center studies with small cohorts and short-term follow-

up periods [8-11]. In our study we compare 5-year biochemical recurrence-free survival (BCRFS) in patients with pT3b after RRP or RALP from the Seoul National University Hospital (SNUH) prostate cancer database. The SNUH commenced in robot assisted laparoscopic radical prostatectomy since May 2008.

Material and Methods

The Institutional Review Boards (IRBs) of the Seoul National University Hospital approved this study (Approval number: H-1608-118-791). As the present study was carried out retrospectively, written informed consent from patients was waived by the IRBs. Personal identifiers were completely removed, and the data were analyzed anonymously. Our study was conducted according to the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

The SNUH database was queried for all patients with prostate cancer who were treated with radical prostatectomy from 1999 to 2015. Among the 2680 patients who underwent radical prostatectomy, 331 patients with seminal vesicle invasion (SVI) (pT3b disease) were identified. The SVI diagnosis was confirmed using standard protocols with SVI defined as a tumor invading the muscular wall of the seminal vesicle (SV). After excluding patients with bone metastasis and those who underwent laparoscopic prostatectomy, 331 patients with pT3bN0-1M0 prostate cancer remained. All patients underwent radical prostatectomy by either RRP or RALP. The number of patients who underwent immediate radiation treatment was 17 (5%), the number of patients who underwent salvage radiation treatment was 26 (7.8%). Retropubic radical prostatectomy (RRP) or robot-assisted laparoscopic prostatectomy (RALP) was conducted by several surgeons during the involving period. A pelvic lymph node dissection (PLND) was performed in 241 of the 331 men based on individual surgeon preference.

Patient data were collected by physicians at diagnostic, preoperative, and postoperative evaluations. The data included preoperative clinical characteristics (PSA level, clinical stage, and biopsy Gleason scores) and pathologic characteristics (disease stage, histology, and surgical margin (SM) status) of the specimens carefully registered by a specialized staff pathologist with genitourinary expertise.

Prostate specimens were staged using the 2002 tumor, node, metastasis (TNM) classification. The percent tumor volume was determined by dividing the sum of all visually estimated tumor foci by the prostate volume on each section. The positive surgical margin was defined as the tumor extending to the inked surface of the specimen and in areas without a definite, identifiable capsule [12]. All histologic slides were reviewed by hospital staff pathologist, and past report was changed, which recorded using grade classification according to 1973 World Health Organization (WHO) classification (G1/G2/G3) to report using grade classification according to 2004 WHO classification (Low grade/High grade). Gleason scores were determined according to the International Society of Urological Pathology modified Gleason grading system [13]. Supersensitive PSA levels were measured every 3 months after surgery during the first year, then every 6 months up to 3-years, and annually thereafter. The median follow-up period was 49 months (mean 55.0±35.9 months). Median follow-up period for RRP was 58 months, while the median follow-up for RALP was 41 months. The primary endpoint was BCR, defined as two consecutive postoperative PSA values >0.2 ng/ml. In case of determining PSA level more than 0.2, PSA levels checked in short term 1 to 3 months considering rising velocity.

Appropriate comparative tests (t-test and chi-square tests) were used to determine differences in patient clinicopathological characteristics. The Kaplan-Meier method was used to determine 5-year BCRFS rates and compare with log-rank tests. Univariate and multivariate Cox proportional hazard models were used to determine predictive factors for BCR. The variables identified as significant in the univariate analysis were then entered into a multivariate Cox regression model to evaluate definitive predictors. All analysis was done using SPSS version 21 (Armonk, NY: IBM Corp.) and statistical significance was defined as p<0.05.

Results

In the entire cohort, 231 (69.7%) patients were treated by RRP and 100 (30.2%) were treated with RALP. The clinical and pathological characteristics are summarized in Table 1.

Clinicopathological parameters of pT3b patients

Total RRP RALP

Number of patient, n (%) 331 (100) 231(69.7) 100(30.3)

Age, [Mean ± SD] 66.3±6.9 66.7±6.7 65.4±7.4

Preoperative PSA, ng/ml, [Mean ± SD] 25.4±37.4 29.3±43.1 16.4±15.4**

PSA group, n (%)

<10 ng/ml 109 (32.9) 66 (28.5) 43 (43)

>10-20 ng/ml 96 (29) 61 (26.4) 35 (35)

>20 ng/ml 126 (38) 104 (45)- 22 (22) **

SVI laterality, n (%)

Unilateral 54 (16.3) 35 (15.1) 19 (19)

Bilateral 45 (13.5) 23 (9.9) 22 (22)

Missing data 232 (70.0) 173 (74.8) 59 (59)*

Tumor volume [Mean ± SD] 19.9±16.9 20.2±15.1 14.1±11.9*

ECE, n [%)

No 57 (17.2) 36 (15.5) 21 (21)

Yes 274(82.7) 195 (84.4) 79 (79)

pGs, n [%)

<7 194(58.6) 124 (53.6) 70 (70)

>8 111 (33.5) 84(36.3) 27 (27)

Missing data 26(7.9) 23(9.9) 3(3)*

LNI, n [%)

Negative 189 (57.1) 114(49.3) 75 (75)

Positive 57 (17.2) 32 (13.8) 25 (25)

SM, n [%)

Negative 98 (29.6) 67 (29) 31 (31)

Positive 233 (70.3) 164 (70.9) 69 (69)

PNI, n [%)

Negative 35 (10.5) 18 (7.7) 17 (17)

Positive 211(63.7) 128 (55.4) 83 (83)

Missing data 85(25.6) 85 (36.7) -

Patients with BCR, n (%) 94 (28.3) 71 (30.7) 23 (23)

Multicentricity, n (%)

Yes 124 (37.4) 73 (31.6) 51(51)

No 121 (36.5) 73 (31.6) 48(48)

Missing 86(25.9) 85(36.7) 1(1)

Capra-S score, [Mean ± SD] 8.2±2.1 8.3±2.1 7.8±2

The mean patient age was 66.3±6.9 years, the mean PSA was 25.4±37.4, and the mean CAPRA-S score was 8.2±2.1. A total of 54 (16.3%) patients had unilateral SVI, 274(82.7%) had extracapsular extension (ECE), 111(33.5%) patients had pathologic Gleason score (pGs) 8 or more, 58 (17.5%) patients had lymph node involvement (LNI), 233(70.3%) patients had a positive surgical margin (PSM). Perineural invasion (PNI) rate was positive in 211 (63.7%) patients. The average yield of LN's removed was 58% and the average yield of positive lymph nodes were 17.5%.

At a median follow-up of 49 months, 94 (28.3%) patients experienced BCR. Kaplan-Meier survival analysis for the overall cohort showed estimated 5- and 10-year BCR free rates of 59% and 42.9%, respectively (Figure 1a). Table 2 summarizes the data of the univariable and multivariable analyses for predictors of BCR. Among the clinicopathologic features, positive lymph node involvement (HR=2.21, p=0.02) was the strongest predictor of BCR.

BCRFS rates stratified by positive lymph node involvement (n=57, 17.2%) versus negative involvement (n=189, 57.1%) are presented in Figure 2a. Log-rank tests revealed that rates of freedom from BCR are significantly lower in patients with positive lymph node involvement (x2(1)=6.62, p=0.01).

Comparison of BCRFS rates stratified by Capra-S score

Follow up period, month Follow UP Period'month

Figure 1 - Kaplan-Meier BCRFS curves for the entire cohort (a) and stratified by operation type (b).

showed that 5-year BCRFS rates were higher in patients with Capra-S scores between 3-5 than in patients with Capra-S scores >6 (72.5% vs. 56.8%), but differences were not statistically significant in log-rank tests (x2(1)=2.570, p=0,10) (Figure 2b). In univariable Cox proportion analysis, the Capra-S score did not predict BCR.

Main clinicopathologic characteristics of patients who underwent either RRP or RALP are presented in Table 1.

Variables including age, ECE, LNI, surgical margin (SM), PNI, multicentricity and Capra-S score were similar between the RRP and RALP groups. The mean PSA level, SVI laterality, tumor volume, and pGs were lower in the RALP cohort. There were no statistically significant differences in 5- year BCRFS rates among RRP and RALP patients (58.1% vs. 65.0%, p=0.3) (Figure 1b).

Discussion

Invasion of prostate cancer into the seminal vesicle is related to poor prognosis and is considered a strong predictor of BCR [13, 14]. In current literature, only a few huge multicenter studies with large descriptive cohorts have been published reporting comparative analysis of outcomes after RRP and RALP treatment in patients with seminal vesicle invasion. Only limited data are available regarding long-term follow-up of oncologic outcomes among RRP and RALP cohorts. In our present study we compared 5-year BCRFS rates after RRP or RALP in patients with pT3b stage (Table 3).

Five-year BCRFS rates were 59% in the pT3b patients in our study: this corresponds with previously reported data from large multi-institutional series [4, 13, 15-17] (Table 3). Patients with isolated SVI on prostate specimen after RP had a 5-year BCRFS rate between 5 and 60%, with a median value of 36% [7]. Because of such wide spectrum of BCRFS rates, additional stratification of risk would be helpful in choosing further treatment [18]. The direction of our research was seeking predictors of BCR in pT3b patients, which helps to make a decision about adjuvant treatment.

Positive lymph node involvement was found in 17.2% of patients and differences in BCRFS rates stratified by lymph node involvement positivity was statistically significant as in previous reports [13, 15]. Lymph node metastasis has been associated with worse cancer-specific survival and a higher rate

Cox regression analysis predicting biochemical recurrence (BCR) rate

Univariable analysis BCR

HR CI

Prostate volume 1.000 (0.98, 1.01)

In PSA

0-10 ref -

10-20 1.079 (0.66, 1.74)

>20 1.035 (0.62, 1.72)

pGs sum 1.001 (0.99, 1.00)

pGs <7 ref

pGs 8 0.834 (0.51, 1.35)

pGs >8 1.445 (0.69, 2.99)

ECE (positive vs negative) 1.016 (0.78, 1,31)

Bilateral ECE 30.65 (0.00, 34,97)

Perineural inv (posit vs negative) 0.432 (0.15, 1.20)

LNI (posit vs negative)* 2.12 (1.17, 3.83)

SVI laterality (bilateral vs unilateral) 0.723 (0.27, 1.87)

Operation type RRP vs RALP 0.959 (0.59,1.54)

PSM 1.043 (0.67, 1.60)

Multicentricity 1.034 (0.58, 1.82)

Capra Score

3-5 ref -

6-7 0.579 (0.27, 1.21)

8-12 1.112 (0.70, 1.75)

Number of positive lymph nodes 1.048 (0.87, 1.26)

Total lymph nodes removed 1.004 (0.97, 1.03)

Tumor volume >36% 0.690 (0.24, 1.95)

Multivariable analysis BCR

LNI (posit vs negative)* 2.21 (1.08, 4.53)

Figure 2 - Kaplan-Meier BCRFS curves for the entire cohort (a) and stratified by operation type (b).

Table 3

Comparison with previous studies

Pierorazio et al.[4] Pagano et al. [15] Kang et al. [16] Secin et al [13] Forgues et al [6] Our study

Patients number 989 180 876 387 104 331

Age, mean 59 (40-73) 63.7 (58-67) 65.8±6,6 62 (56-66) 63.5(58-67) 66.3±6.9

Preoperative PSA ng/ml, mean 7.2 (0.8-67) 9.1(6.3-17.1) 22.3±26.0 10.8(6.9-20.3) 10.3(7-15) 25.4±37.4

Preoperative PSA group, n (%)

<10 ng/ml - 101(56.1) - 168(46) - 109 (32.9)

>10-

20ng/ml 42(23.3) 103(28) 96 (29)

>20 ng/ml 37(20.6) 92(25) 126 (38)

pGs, n (%)

<6 92(9.3) 94(12.4) 15(14.4)

7 542(54.8) 126(70) 398(49.7) 321(42.6) 71(68.3) 194 (58.6)

>8 352(35.5) 54(30) 403(50.3) 336(44.6) 18(17.3) 111 (33.5)

Lymph node involvement, n (%) 242(24.2) 22(12.2) 130(16.2) 91(24) - 57 (17.2)

PSM, n (%) 409(41.3) 74(41.1) 524(65.4) 146(38) 34(32.7) 233(70.3)

5 year BCRFS, % 36-40 39.5 30.1 38 55.8 59

of distant metastasis [19]. Positive lymph node involvement status was also found to be a statistically significant predictor of BCR in multivariate analysis in our cohort. These patients may benefit from early adjunctive therapy after surgery to improve outcomes.

The pGs was not a predictor of BCR as in our study, unlike in previous studies [5, 11]. Among the different prognosis factors, the presence of PSM appears to be the most important [7]. PSM rate in the entire cohort of patients with pT3b was 70.3%: this rate is higher than that in the findings from previous series in which rates of 41.3% [4], 38% [13], and 41.1% [15] were reported. PSM rates among two treatment method groups not revealed differences in PSM status in patients who underwent RRP and RALP (70.9% vs. 69%). Kaplan-Meier plots showed that BCRFS was higher in patients with PSM but differences in the log-rank test were not statistically significant (x2(1)=0.037, p=0.8). The 5-year BCRFS rate was 59.3% in patients with PSM status, whereas in patients with negative surgical margin status the rate was 58.2%. Spahn et al [20] conducted a multivariate analysis of pT3b patients that demonstrated that SM status was an independent predictive factor of prostate cancer BCR. In previously reported studies [21, 22] PSM was independent

predictive factor of BCR in pT2 and pT3a patients, but not in pT3b patients. In our pT3b cohort also, PSM was not found as a prognostic factor in univariate and multivariate analysis. As in the study of Yang et al. [23] where Kaplan-Meier analysis stratified by CAPRA-S scores of 3-5 vs. > 6 resulted in differences among groups, in our cohort BCRFS rates also decreased with increasing Capra-S score. The 5-year BCRFS was higher in pT3b patients with Capra-S scores 3-5 vs. >6, but log-rank test (x2(1)=2.57, p=0.109) did not reveal statistically significant differences among the groups. This is likely due to small sample size because there were not any such problematic values in large CaPSURE [24, 25] and SEARCH data-sets [26]. Cox proportional regression did not demonstrate a prognostic probability of the Capra-S score in univariate analysis.

In Punnen et al.s" study [27] 4-year BCRFS rates after RRP and RALP were determined to be 66% vs. 68% respectively and differences among BCRFS rates were not significant. After that Pierorazio et al [28] and Menon et al [11] established 3-year and 5-year BCRFS rates, respectively, and they did not find statistically significant differences between the RRP and RALP cohorts. In our study BCRFS rates were lower in RRP group (58.1%) than in RALP group (65%), but differences were not

statistically significant. Therefore our study demonstrated comparable BCRFS rates stratified by operation type in pT3b patients similar to previous reports.

Our present study has several limitations resulting from its retrospective design, such as a small sample size and a small number of death events which limited the power to detect differences among variables. Further, the mean follow-up remains short and longer observation time and additional studies are required, especially with regard to overall survival and cancer specific survival.

Conclusion

Patients with positive lymph node involvement, have a poor prognosis. The Capra-S score was unable to predict BCR in pT3b patients. RALP is comparable to RRP for prostate cancer with seminal vesicle invasion with respect to BCR.

Clinical Practice Points

Five-year BCRFS rates in the pT3b patients in our study corresponds with previously reported data from large multi-institutional series.

There were no statistically significant differences in 5-year BCRFS rates among RRP and RALP patients.

Univariate and multivariate analyses have identified positive lymph node invasion as a poor prognostic factor.

Capra-S score was unable to predict BCR in pT3b stage prostate cancer patients

Abbreviations

BCR: biochemical recurrence, RRP: retropubic radical prostatectomy, RALP: robot-assisted laparoscopic prostatectomy, BCRFS: biochemical recurrence-free survival, SVI: seminal vesicle invasion, SNUH: Seoul National University Hospital, IRB: Institutional Review Boards, SD = standard deviation, pGs = pathologic Gleason score, pN = pathologic n stage, SV: seminal vesicle, PSA: Prostate-specific antigen, TNM: Tumor Node Metastasis, ECE: extracapsular extension, LNI: lymph node involvement, PSM: positive surgical margin, PNI: Perineural invasion, CSS: cancer specific survival, OS overall survival.

Declarations Acknowledgments

We would like to appreciate the reviewers for theirs helpful suggestions or commons on this paper.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Availability of data and materials

The dataset analyzed during the current study available from the corresponding author on reasonable request.

Open Access

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Competing interests

The authors declare no conflict of interest.

Consent for publication

Not applicable (the manuscript does not include details, images, or videos to individual participants).

Ethical approval and consent to participate

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was performed under approval of the appropriate ethics committee (Institutional Review Boards (IRBs) of the Seoul National University Hospital approved this study (Approval number: H-1608-118-791).

Authors" contributions

UB had full access to all the data in the study and takes responsibility for the intergrity of the data and accuracy of the data analysis. UBB, JKK, CWJ, JHK, and CK designed the study. UB, JKK, BT, and MK performed data acquisition. UB and JKK analyzed and interpreted the data. UB and CWJ drafted the manuscript. CWJ performed critical revisions. UB, JKK, and BT performed the statistical analysis. CWJ, HHK, JHK, and CK supervised the study.

Disclosures: There is no conflict of interest for all authors.

References

1. Lee HM, Solan MJ, Lupinacci P, Gomella LG, Valicenti RK: Long-term outcome of patients with prostate cancer and pathologic seminal vesicle invasion (pT3b): effect of adjuvant radiotherapy. Urology 2004, 64(1):84-89.

2. D'Amico AV, Whittington R, Malkowicz SB, Schultz D, Schnall M, Tomaszewski JE, Wein A: A multivariate analysis of clinical and pathological factors that predict for prostate specific antigen failure after radical prostatectomy for prostate cancer. The Journal of urology 1995, 154(1):131-138.

3. Bostwick DG, Qian J, Bergstralh E, Dundore P, Dugan J, Myers RP, Oesterling JE: Prediction of capsular perforation and seminal vesicle invasion in prostate cancer. The Journal of urology 1996, 155(4):1361-1367.

4. Pierorazio PM, Ross AE, Schaeffer EM, Epstein JI, Han M, Walsh PC, Partin AW: A contemporary analysis of outcomes of adenocarcinoma of the prostate with seminal vesicle invasion (pT3b) after radical prostatectomy. The Journal of urology 2011, 185(5):1691-1697.

5. Abdollah F, Suardi N, Cozzarini C, Gallina A, Capitanio U, Bianchi M, Sun M, Fossati N, Passoni NM, Fiorino C et al: Selecting the optimal candidate for adjuvant radiotherapy after radical prostatectomy for prostate cancer: a long-term survival analysis. European urology 2013, 63(6):998-1008.

6. Forgues A, Rozet F, Audenet F, Ouzzane A, Sanchez-Salas R, Barret E, Galiano M, Prapotnich D, Cathelineau X: Oncologic outcomes after minimally invasive radical prostatectomy in patients with seminal vesicle invasion (pT3b) without adjuvant therapy. World journal of urology 2014, 32(2):519-524.

7. Siddiqui SA, Boorjian SA, Blute ML, Rangel LJ, Bergstralh EJ, Karnes RJ, Frank I: Impact of adjuvant androgen deprivation therapy after radical prostatectomy on the survival of patients with pathological T3b prostate cancer. BJU international 2011, 107(3):383-388.

8. Sooriakumaran P, Haendler L, Nyberg T, Gronberg H, Nilsson A, Carlsson S, Hosseini A, Adding C, Jonsson M, Ploumidis A et al: Biochemical recurrence after robot-assisted radical prostatectomy in a European single-centre cohort with a minimum follow-up time of 5 years. European urology 2012, 62(5):768-774.

9. Liss MA, Lusch A, Morales B, Beheshti N, Skarecky D, Narula N, Osann K, Ahlering TE: Robot-assisted radical prostatectomy: 5-year oncological and biochemical outcomes. The Journal of urology 2012, 188(6):2205-2210.

10. 10. Suardi N, Ficarra V, Willemsen P, De Wil P, Gallina A, De Naeyer G, Schatteman P, Montorsi F, Carpentier P, Mottrie A: Long-term biochemical recurrence rates after robot-assisted radical prostatectomy: analysis of a single-center series of patients with a minimum follow-up of 5 years. Urology 2012, 79(1):133-138.

11. Menon M, Bhandari M, Gupta N, Lane Z, Peabody JO, Rogers CG, Sammon J, Siddiqui SA, Diaz M: Biochemical recurrence following robot-assisted radical prostatectomy: analysis of 1384 patients with a median 5-year follow-up. European urology 2010, 58(6):838-846.

12. Rosen MA, Goldstone L, Lapin S, Wheeler T, Scardino PT: Frequency and location of extracapsular extension and positive surgical margins in radical prostatectomy specimens. The Journal of urology 1992, 148(2 Pt 1):331-337.

13. Secin FP, Bianco FJ, Jr., Vickers AJ, Reuter V, Wheeler T, Fearn PA, Eastham JA, Scardino PT: Cancer-specific survival and predictors of prostate-specific antigen recurrence and survival in patients with seminal vesicle invasion after radical prostatectomy. Cancer 2006, 106(11):2369-2375.

14. Stephenson AJ, Kattan MW, Eastham JA, Bianco FJ, Jr., Yossepowitch O, Vickers AJ, Klein EA, Wood DP, Scardino PT: Prostate cancer-specific mortality after radical prostatectomy for patients treated in the prostate-specific antigen era. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2009, 27(26):4300-4305.

15. Pagano MJ, Whalen MJ, Paulucci DJ, Reddy BN, Matulay JT, Rothberg M, Scarberry K, Patel T, Shapiro EY, RoyChoudhuiy A et al: Predictors of biochemical recurrence in pT3b prostate cancer after radical prostatectomy without adjuvant radiotherapy. The Prostate 2016, 76(2):226-234.

16. Kang DI, Chung JI, Ha HK, Min K, Yoon J, Kim W, Seo WI, Kang P, Jung SJ, Kim IY: Korean prostate cancer patients have worse disease characteristics than their American counterparts. Asian Pacific journal of cancer prevention : APJCP 2013, 14(11):6913-6917.

17. Bastide C, Rossi D, Lechevallier E, Bladou F, Barriol D, Bretheau D, Grisoni V, Mancini J, Giusiano S, Eghazarian C et al: Seminal vesicle invasion: what is the best adjuvant treatment after radical prostatectomy? BJU international 2012, 109(4):525-530; discussion 531-522.

18. Sofer M, Savoie M, Kim SS, Civantos F, Soloway MS: Biochemical and pathological predictors of the recurrence of prostatic adenocarcinoma with seminal vesicle invasion. The Journal of urology 2003, 169(1):153-156.

19. Bader P, Burkhard FC, Markwalder R, Studer UE: Disease progression and survival of patients with positive lymph nodes after radical prostatectomy. Is there a chance of cure? The Journal of urology 2003, 169(3):849-854.

20. Spahn M, Briganti A, Capitanio U, Kneitz B, Gontero P, Karnes JR, Schubert M, Montorsi F, Scholz CJ, Bader P et al: Outcome predictors of radical prostatectomy followed by adjuvant androgen deprivation in patients with clinical high risk prostate cancer and pT3 surgical margin positive disease. The Journal of urology 2012, 188(1):84-90.

21. Ploussard G, Agamy MA, Alenda O, Allory Y, Mouracade P, Vordos D, Hoznek A, Abbou CC, de la Taille A, Salomon L: Impact of positive surgical margins on prostate-specific antigen failure after radical prostatectomy in adjuvant treatment-naive patients. BJU international 2011, 107(11):1748-1754.

22. Ohori M, Wheeler TM, Kattan MW, Goto Y, Scardino PT: Prognostic significance of positive surgical margins in radical prostatectomy specimens. The Journal of urology 1995, 154(5):1818-1824.

23. Yang Y, Luo Y, Hou GL, Huang QX, Pang J, Gao X: Laparoscopic Radical Prostatectomy Plus Extended Lymph Node Dissection in Combination With Immediate Androgen Deprivation Therapy for Cases of pT3-4N0-1M0 Prostate Cancer: A Multimodal Study of 8 Years' Follow-up. Clinical genitourinary cancer 2015.

24. Seo WI, Kang PM, Kang DI, Yoon JH, Kim W, Chung JI: Cancer of the Prostate Risk Assessment (CAPRA) Preoperative Score Versus Postoperative Score (CAPRA-S): ability to predict cancer progression and decision-making regarding adjuvant therapy after radical prostatectomy. Journal of Korean medical science 2014, 29(9):1212-1216.

25. Cooperberg MR, Hilton JF, Carroll PR: The CAPRA-S score: A straightforward tool for improved prediction of outcomes after radical prostatectomy. Cancer 2011, 117(22):5039-5046.

26. Punnen S, Freedland SJ, Presti JC, Jr., Aronson WJ, Terris MK, Kane CJ, Amling CL, Carroll PR, Cooperberg MR: Multi-institutional validation of the CAPRA-S score to predict disease recurrence and mortality after radical prostatectomy. European urology 2014, 65(6):1171-1177.

27. Punnen S, Meng MV, Cooperberg MR, Greene KL, Cowan JE, Carroll PR: How does robot-assisted radical prostatectomy (RARP) compare with open surgery in men with high-risk prostate cancer? BJU international 2013, 112(4):E314-E320.

28. Pierorazio PM, Mullins JK, Eifler JB, Voth K, Hyams ES, Han M, Pavlovich CP, Bivalacqua TJ, Partin AW, Allaf ME et al: Contemporaneous comparison of open vs minimally-invasive radical prostatectomy for high-risk prostate cancer. BJU international 2013, 112(6):751-757.

How to cite this article: Ulanbek Zhanbyrbekuly, Jung Kwon Kim, Minyong Kang, Bumsik Tae, Ja Hyun Ku, Hyeon Hoe Kim, Chang Wook Jeong, Cheol Kwak. Prognostic variables associated with biochemical recurrence after radical prostatectomy for pT3b prostate cancer. J Clin Med Kaz. 2018; 1(47):29-35