Invasion of seminal vesicles by adenocarcinoma of the prostate: PSA outcome determined by preoperative and postoperative factors

doi:10.1016/j.urology.2003.09.042

Urology

Volume 63, Issue 2, February 2004, Pages 333-336

https://doi.org/10.1016/j.urology.2003.09.042 Get rights and content

Abstract

Objectives

To determine which preoperative and postoperative factors were predictive of the time to prostate-specific antigen (PSA) failure after radical retropubic prostatectomy (RRP) for patients with seminal vesicle invasion (SVI). SVI by prostate cancer is associated with high PSA failure rates after RRP and subsequent distant metastases.

Methods

Between 1988 and 2002, 1697 patients with prostate cancer underwent RRP at Brigham and Women's Hospital, of whom 103 (6%) had SVI. Cox regression multivariable analysis was used to determine whether the preoperative PSA level, prostatectomy Gleason score, margin status, or presence of extraprostatic extension was predictive of the time to postoperative PSA failure. Estimates of PSA outcome were made using the actuarial method of Kaplan and Meier for patients who had none, all, or at least one of the factors that predicted for the time to postoperative PSA failure.

Results

The statistically significant categorical predictors of the time to PSA failure after RRP in patients with SVI included prostatectomy Gleason score of 4+3 or greater (P = 0.009), preoperative PSA level greater than 20 ng/dL when evaluated as a categorical or as a continuous variable (P = 0.002 and P = 0.001, respectively), and margin positivity (P = 0.075) which was of borderline significance. The 3-year estimate of PSA control was 52% to 100%, 28%, and 0% for patients with negative margins, preoperative PSA less than 20 ng/dL, and prostatectomy Gleason score of 3+4 or less versus having one to two or all three predictors of the time to postoperative PSA failure.

Conclusions

The PSA outcome after RRP for patients with SVI varies depending on the preoperative PSA level, prostatectomy Gleason score, and margin status.

Section snippets

Patient selection and treatment

Between 1988 and 2002, 1697 patients with American Joint Committee on Cancer (2002) clinical Stage T1 or T2 prostate cancer underwent RRP at the Brigham and Women's Hospital (Table I). Serum PSA levels were drawn within 1 month before surgery. All patients underwent limited bilateral pelvic lymph node dissection. Obturator nodes were sampled from between the external iliac vein and the obturator nerve. The surgical specimens were pathologically examined after removal to evaluate the SVs,

Results

The significant categorical predictors of the time to PSA failure after RRP in patients with SVI included prostatectomy Gleason score of 4+3 or greater (P = 0.009) and preoperative PSA greater than 20 ng/dL (P = 0.002); margin positivity (P = 0.075) was of borderline significance. The presence of extraprostatic extension was not a statistically significant predictor of postoperative PSA failure (P = 0.272). When evaluated as continuous variables, both the preoperative PSA level (P = 0.001) and

Comment

SVI by prostate cancer is becoming less frequently identified in pathologic specimens after RRP given the use of PSA screening and early detection. Historically, involvement of the SVs at the time of RRP had been considered a poor prognostic indicator.5 Blute and colleagues6 found, in a group of 2518 patients treated with RRP, that those who were found to have SVI by tumor cells or micrometastases experienced a lower 5-year progression-free survival (52% in patients with SVI versus 81% in

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Cited by (32)

A novel imaging based Nomogram for predicting post-surgical biochemical recurrence and adverse pathology of prostate cancer from pre-operative bi-parametric MRI
2021, EBioMedicine
Citation Excerpt :
However, approximately 20% to 40% of patients experience biochemical recurrence (BCR) who may further develop metastasis after definitive treatment [2–4]. In addition, it has been shown that 25% of patients with low PCa volume and biopsy Gleason Grade Group (GG) 2 harbor adverse pathology (AP) [5], which is known to be a predictor for developing BCR and subsequent metastasis [6,7], and thus indicates exclusion of active surveillance [8]. Several tools have been proposed to identify patients at risk of presence of AP at final pathology [8], developing BCR [9,10], and subsequent metastasis [9–11].
We developed and validated an integrated radiomic-clinicopathologic nomogram (RadClip) for post-surgical biochemical recurrence free survival (bRFS) and adverse pathology (AP) prediction in men with prostate cancer (PCa). RadClip was further compared against extant prognostics tools like CAPRA and Decipher.
A retrospective study of 198 patients with PCa from four institutions who underwent pre-operative 3 Tesla MRI followed by radical prostatectomy, between 2009 and 2017 with a median 35-month follow-up was performed. Radiomic features were extracted from prostate cancer regions on bi-parametric magnetic resonance imaging (bpMRI). Cox Proportional-Hazards (CPH) model warped with minimum redundancy maximum relevance (MRMR) feature selection was employed to select bpMRI radiomic features for bRFS prediction in the training set (D₁, N = 71). In addition, a bpMRI radiomic risk score (RadS) and associated nomogram, RadClip, were constructed in D₁ and then compared against the Decipher, pre-operative (CAPRA), and post-operative (CAPRA-S) nomograms for bRFS and AP prediction in the testing set (D₂, N = 127).
“RadClip yielded a higher C-index (0.77, 95% CI 0.65-0.88) compared to CAPRA (0.68, 95% CI 0.57-0.8) and Decipher (0.51, 95% CI 0.33-0.69) and was found to be comparable to CAPRA-S (0.75, 95% CI 0.65-0.85). RadClip resulted in a higher AUC (0.71, 95% CI 0.62-0.81) for predicting AP compared to Decipher (0.66, 95% CI 0.56-0.77) and CAPRA (0.69, 95% CI 0.59-0.79).”
RadClip was more prognostic of bRFS and AP compared to Decipher and CAPRA. It could help pre-operatively identify PCa patients at low risk of biochemical recurrence and AP and who therefore might defer additional therapy.
The National Institutes of Health, the U.S. Department of Veterans Affairs, and the Department of Defense.
Lymph node yield during radical prostatectomy does not impact rate of biochemical recurrence in patients with seminal vesicle invasion and node-negative disease
2018, Urologic Oncology: Seminars and Original Investigations
Citation Excerpt :
In distinction, establishing lymph node invasion is much more variable due to lack of consistency for which men undergo PLND, the number of nodes removed, and the area(s) resected. Similarly, other at-risk characteristics such as positive surgical margins or sites of extraprostatic extension can be misrepresented, simply because seminal vesicles are easier to pathologically assess [23–29]. This is the first report to focus on the potential of reducing BCR in men undergoing PLND with SVI who had no adjuvant therapy. In this highly selected group with SVI (with and without PLND), the unadjusted risk of BCR at 3 years was 61.1%.
Seminal vesicle invasion (SVI) is a risk factor for poor oncologic outcome in patients with prostate cancer. Modifications to the pelvic lymph node dissection (PLND) during radical prostatectomy (RP) have been reported to have a therapeutic benefit. The present study is the first to determine if lymph node yield (LNY) is associated with a lower risk of biochemical recurrence (BCR) for men with SVI.
A total of 220 patients from 2 high-volume institutions who underwent RP without adjuvant treatment between 1990 and 2015 and had prostate cancer with SVI (i.e., pT3b) were identified, and 21 patients did not undergo lymph node dissection. BCR was defined as a postoperative PSA>0.2 ng/mL, or use of salvage androgen deprivation therapy (ADT) or radiation. Multivariable Cox proportional hazards models were used to determine whether LNY was predictive of BCR, controlling for PSA, pathologic Gleason Score, pathologic lymph node status, NCCN risk category, etc. The Kaplan-Meier method was used to determine 3-year freedom from BCR.
Median number of lymph nodes sampled were 7 (IQR: 3–12; range: 0–35) and 90.5% underwent PLND. The estimated 3-year BCR rate was 43.9%. Results from multivariable analysis demonstrated that LNY was not significantly associated with risk of BCR overall (HR = 1.00, 95% CI: 0.98–1.03; P = 0.848) for pN0 (HR = 0.99, 95% CI: 0.97–1.03; P = 0.916) or pN1 patients (HR = 0.96, 95% CI: 0.88–1.06; P = 0.468). Overall, PSA (HR = 1.02, P<0.001) and biopsy Gleason sum ≥ 8 (HR = 1.81, P = 0.001) were associated with an increased risk of BCR, and increasing LNY increased the likelihood of detecting>2 positive lymph nodes (OR = 1.27, 95% CI: 1.06–1.65, P = 0.023).
Seminal vesicle invasion is associated with an increased risk of BCR at 3 years, primarily due to pathologic Gleason score and PSA. Although greater lymph node yield is diagnostic and facilitates more accurate pathologic staging, our data do not show a therapeutic benefit in reducing BCR.
A contemporary analysis of outcomes of adenocarcinoma of the prostate with seminal vesicle invasion (pT3b) after radical prostatectomy
2011, Journal of Urology
Citation Excerpt :
The factors most likely to predict biochemical recurrence were advanced clinical stage (greater than T2b), intermediate7 or high risk8–10 pathological Gleason sum, and positive SMs. Multiple series have demonstrated that preoperative PSA, Gleason sum and SM positivity predict BFS.1,6,7,17 PSA was not an important predictor of outcome on multivariate analysis, most likely since our approach focused more directly on the PSA era, so that PSA levels were truncated by improved screening and detection.
Despite earlier detection and stage migration, seminal vesicle invasion is still reported in the prostate specific antigen era and remains a poor prognostic indicator. We investigated outcomes in men with pT3b disease in the contemporary era.
The institutional radical prostatectomy database (1982 to 2010) of 18,505 men was queried and 989 with pT3b tumors were identified. The cohort was split into pre-prostate specific antigen (1982 to 1992), and early (1993 to 2000) and contemporary (2001 to present) prostate specific antigen eras. Of the 732 men identified in the prostate specific antigen era 140 had lymph node involvement and were excluded from study. The Kaplan-Meier method was used to determine biochemical recurrence-free, metastasis-free and prostate cancer specific survival. Proportional hazard models were used to determine predictors of biochemical recurrence-free, metastasis-free and cancer specific survival.
In the pre-prostate specific antigen, and early and contemporary prostate specific antigen eras, 7.7%, 4.3% and 3.3% of patients, respectively, had pT3bN0 disease (p >0.001). In pT3bN0 cases, the 10-year biochemical recurrence-free survival rate was 25.8%, 28.6% and 19.6% (p = 0.8), and the cancer specific survival rate was 79.9%, 79.6% and 83.8% (p = 0.6) among the eras, respectively. In pT3bN0 cases in the prostate specific antigen era, prostate specific antigen, clinical stage T2b or greater, pathological Gleason sum 7 and 8–10, and positive surgical margins were significant predictors of biochemical recurrence-free survival on multivariate analysis while clinical stage T2c or greater and Gleason 8–10 were predictors of metastasis-free and cancer specific survival.
Despite a decreased frequency of pT3b disease, and lower rates of positive surgical margins and lymph nodes, patients with seminal vesicle invasion continue to have low biochemical recurrence-free survival. Advanced clinical stage, intermediate or high risk Gleason sum at pathological evaluation and positive surgical margins predict biochemical recurrence. High risk clinical stage and Gleason sum predict metastasis-free and cancer specific survival.
Predictive histological parameters of seminal vesicle invasion in prostate cancer
2008, Revista Espanola de Patologia
La invasión de las vesículas seminales es un dato histológico de mal pronóstico en el cáncer de próstata. En la mayor parte de los casos es un hallazgo accidental ya que los pacientes con signos clínicos o histológicos de enfermedad extraprostática no se tratan mediante cirugía en la mayor parte de protocolos al uso. Nuestra intención es cuantificar este hallazgo histológico en una serie homogénea de prostatectomías radicales y correlacionarlo con los hallazgos en las biopsias previas.
Durante un periodo de 8 años (1998-2005), 363 pacientes con cáncer de próstata fueron tratados mediante prostatectomía radical en el Hospital de Basurto. Los pacientes fueron seleccionados para la cirugía en función de la combinación de la estadificación clínica, niveles de PSA sérico y datos obtenidos de la biopsia previa. Los datos obtenidos en las prostatectomías se correlacionaron (rho de Spearman) con varios hallazgos histológicos procedentes de las biopsias.
Se detectó invasión seminal en 37 pacientes (10,2%). La invasión microscópica de las vesículas seminales se correlacionó con los milímetros totales de cáncer (media 20 mm, ρ=0,397), con el número de focos de tumor (media 3,8, ρ=0,383), con la invasión de ambos lados prostáticos (ρ=0,256), con el índice de Gleason >7 (ρ=0,306), con la invasión perineural (ρ=0,318), y con el PIN de alto grado (ρ=0,142) en las biopsias, y con el índice de Gleason >7 (ρ=0,357), con el PIN de alto grado (ρ=0,211), con la extensión extraprostática (ρ=0,480), y con la invasión de márgenes quirúrgicos (ρ=0,287), invasión perineural (ρ=0,847), y afectación del ápex (ρ=0,307), en las prostatectomías.
La invasión de las vesículas seminales es un hallazgo frecuente en las piezas de prostatectomía radical, incluso después de una selección correcta de pacientes para cirugía. Este hallazgo histológico se correlaciona con parámetros de volumen tumoral, con la invasión bilateral, y con otros parámetros de mal pronóstico en el cáncer de próstata.
Seminal vesicle invasion is a finding of bad prognosis in prostate cancer. Its discovery in radical prostatectomies is accidental in most cases because patients with clinical or histological evidence of extraprostatic disease are not surgically treated in most clinical protocols. Our aim is to quantify this finding in a homogeneous series of radical prostatectomies and to correlate it with core biopsy findings.
Over an 8-year period (1998-2005), a total of 363 patients with prostate cancer underwent radical prostatectomy at Basurto Hospital. The combination of clinical staging, PSA levels and core biopsy data indicated the candidates for surgery. Data obtained in prostatectomies were correlated (Spearman's rho) with several histological parameters in biopsies.
Radical prostatectomies showed seminal vesicle invasion in 37 cases (10.2%). Microscopic seminal vesicle invasion correlated with total millimetres of cancer (average 20 mm, ρ=0.397), number of tumour foci (average 3.8, ρ=0.383), bilateral invasion (ρ=0.256), Gleason Index (GI) >7 (ρ=0.306), perineurial invasion (ρ=0.318), and high grade PIN (HGPIN) (ρ=0.142) in biopsies, and with GI >7 (ρ=0.357), HGPIN (ρ=0.211), extraprostatic extension (ρ=0.480), and margin (ρ=0.287), perineurial (ρ=0.847), and apex (ρ=0.307) invasions, in prostatectomies.
Seminal invasion is a frequent finding in prostatectomies, even after a correct selection of patients for surgery. This finding correlates to tumour volume parameters, bilateral invasion, and other morphologic parameters of bad prognosis in prostate cancer.
Development and Split-Sample Validation of a Nomogram Predicting the Probability of Seminal Vesicle Invasion at Radical Prostatectomy
2007, European Urology
Citation Excerpt :
Specifically, Korman et al [10] suggested that sparing the distal portion of the SVs at RP may be justified without compromising cancer control. A similar trend appeared in the radiation oncology literature: Bloom et al [11] indicated that, in select patients, the tips of the SVs may be safely excluded from the radiation field. However, exclusion of SVs from the surgical specimen or the radiation field was not universally accepted.
Seminal vesicle preservation may have a beneficial impact on erectile and urinary function after radical prostatectomy (RP). We hypothesized that contemporary patients, at very low risk of seminal vesicle invasion (SVI), can be highly accurately identified with an equally contemporary SVI nomogram.
A nomogram predicting SVI was developed in a cohort study of 666 men diagnosed with 10 or more biopsy cores and treated with RP. Biopsy Gleason sum, prostate-specific antigen, clinical stage, and percentage of positive cores represented predictors in multivariable logistic regression models and formed the basis for the nomogram. The regression coefficient-based nomogram was then externally validated in a split-sample cohort of 230 patients. This cohort also served for a head-to-head comparison of external validity of the novel nomogram with two existing tools, namely Partin’s SVI predictions and Koh’s SVI nomogram.
Split-sample validation of the novel SVI nomogram demonstrated 79.2% accuracy versus 75.6% for Partin versus 77.7% for Koh. Our nomogram cutoff of 3% or less had 96.2% negative predictive value for identifying men at very low risk of SVI. This cutoff could have safely allowed omitting the removal of seminal vesicles in 45.2% of RP candidates, if incorrect classification of 1.7% of patients was judged acceptable.
The potential benefits of SV preservation can be safely accomplished in virtually 50% of contemporary men subjected to RP, if our tool’s predictions are applied.
Should the Gleason grading system for prostate cancer be modified to account for high-grade tertiary components? A systematic review and meta-analysis
2007, Lancet Oncology
Citation Excerpt :
Extraprostatic extension was seen with similar frequency in patients with Gleason score 4+4 with (77%, 20 of 26) or without (71%, 65 of 91) a tertiary grade. Invasion of the seminal vesicles by prostate cancer is detected in fewer than 10% of patients, and is widely considered an indicator of poor outcome after radical prostatectomy.28 This invasion has traditionally been associated with occult micro-metastases, as depicted by the high incidence of biochemical failure and the subsequent development of metastatic disease, although the 5-year PSA-progression rate for patients with seminal-vesicle invasion varies between 5% and 60%.29
The Gleason system for grading prostate cancer assigns a score on the basis of the most prevalent and second most prevalent grade. Several studies have investigated the clinical significance of a tertiary grade in radical prostatectomy samples. A systematic search of the published work identified seven studies that reported the prognostic value of a tertiary Gleason grade. Three studies correlated the presence of a tertiary grade with pathological stage, and six with prostate-specific antigen recurrence or clinical progression. In the small number of studies available, the frequency of a tertiary grade was consistently higher in samples characterised with pathological variables of poor outcome, such as extra-prostatic extension and positive surgical margins, but not lymph-node metastases. In five studies the presence of a tertiary grade increased the risk of prostate-specific antigen recurrence after radical prostatectomy by a factor of 2·5. However, modification of the Gleason score to include a tertiary grade in Gleason 4+3 tumours might overestimate the risk of seminal-vesicle or lymph-node invasion. This systematic review has established the association of a tertiary grade with poorer outcome than that associated with no tertiary grade. A tertiary grade should, therefore, be included in the pathological reporting of prostate cancer and be considered in the interpretation and design of clinical trials. However, all studies assessed for this review were retrospective, potentially affected by selection bias, and based on radical prostatectomy samples or transurethral resections rather than biopsy samples. Therefore, more evidence is needed to warrant the adaptation of the Gleason system to account for the presence of a tertiary grade, especially when scoring prostatic biopsies and applying predictive algorithms.

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Adult urologyInvasion of seminal vesicles by adenocarcinoma of the prostate: PSA outcome determined by preoperative and postoperative factors

Abstract

Objectives

Methods

Results

Conclusions

Section snippets

Patient selection and treatment

Results

Comment

Urology

J Urol

J Urol

Urol Clin North Am

J Urol

J Urol

J Urol

Adult urology
Invasion of seminal vesicles by adenocarcinoma of the prostate: PSA outcome determined by preoperative and postoperative factors