Original article
Influence of pathologist experience on positive surgical margins following radical prostatectomy

https://doi.org/10.1016/j.urolonc.2017.02.007Get rights and content

Highlights

  • Greater pathologist experience was associated with greater odds of PSMs after RP.

  • Increasing surgeon experience was associated with decreased odds of PSM.

  • The relationship between pathologist experience and PSMs was nonlinear.

Abstract

Background

A positive surgical margin (PSM) following radical prostatectomy (RP) for prostate cancer is associated with increased risk of biochemical recurrence. We sought to examine whether the pathologist is an independent predictor of PSMs.

Methods

We performed a retrospective review of 3,557 men who underwent RP for localized prostate cancer at our institution from 2003 to 2015. We evaluated 29 separate pathologists. Univariate and multivariable logistic regression were used to test variables previously shown to influence PSM rates.

Results

Overall rate of PSM was 18.9%. Compared with patients without PSM, patients with PSM had higher body mass index (mean: 28.8 vs. 28.3), Gleason score≥7 (84% vs. 66%), extracapsular extension (51% vs. 20%), and median prostate-specific antigen (5.9 vs. 5.1 ng/ml) (all P<0.05). Univariate logistic regression showed that surgeon experience, pathologist experience, and pathologist genitourinary fellowship training were all predictors of PSMs (all P<0.05). Multivariable regression analysis confirmed that decreased surgeon experience, increased pathologist experience, higher pathologic Gleason score, higher pathologic stage, and higher prostate-specific antigen were significant predictors of PSMs. Increasing surgeon experience was associated with decreased odds of PSM (odds ratio = 0.79 per 1 standard deviation increase, 95% CI [0.70–0.89]). In contrast, increasing pathologist experience was associated with increased odds of PSM (odds ratio = 1.11 per 1 standard deviation increase, 95% CI [1.03–1.19]). The relationship between pathologist experience and PSM appeared to be nonlinear (Fig. 2).

Conclusions

Greater pathologist experience appears to be associated with greater odds of PSMs following radical prostatectomy, even after controlling for case mix, pathologist fellowship training, and surgeon experience. Based on these findings, pathologists with less experience reviewing RP specimens may consider requesting rereview by a dedicated genitourinary pathologist.

Introduction

Prostate cancer (PCa) is the most commonly diagnosed nonskin cancer in the United States and radical prostatectomy (RP) is the most common treatment option for men with localized disease [1]. Analysis of the surgical margin following RP, defined as tumor cells present at the inked margin of a resected specimen [2], is frequently used to assist in risk stratification and guide subsequent therapies. Over several decades, there has been continued downward stage migration due to prostate-specific antigen (PSA) screening [3]. Consequently, the rates of positive surgical margins (PSM) after RP have been decreasing over the last 25 years and contemporary rates range from 10% to 30% [4], [5].

PSMs following RP can be a significant source of anxiety for patients and increases the risk of biochemical recurrence [6], [7] and secondary therapies [8]. Although some data suggest PSMs to independently predict PCa-specific mortality [9], most adjusted analyses do not show similar observations [10], [11]. Some expert guidelines (American Society of Clinical Oncology/American Urological Association/European Association of Urology) suggest that men with PSMs should consider adjuvant radiation therapy [12], [13]; however, this is not commonly done [14], [15]. For these reasons, accurate interpretation of the surgical margin has a critical role for patient counseling, prognosis, and treatment decisions [16].

PSA, clinical stage, pathologic stage, and volume of tumor are consistently associated with a higher PSM rate [5], [17], [18], [19]. The role of the pathologist on PSMs has also been examined. Interpretation of surgical margins is subject to interobserver variability with multiple studies suggesting 8% to 26% rates of discordance among pathologists [20], [21].

We hypothesize that the individual pathologist and pathologist experience are associated with PSMs following RP.

Section snippets

Study design and data collection

We performed a retrospective, single-center, observational cohort study on 3,557 men who were treated with robotic-assisted laparoscopic prostatectomy for localized PCa at the University of Chicago Medical Center and Weiss Hospital between April 2003 and January 2015. Men were excluded if surgery was aborted (n = 38, 1%), most often due to intraoperative positive lymph nodes, or if they received neoadjuvant therapy (n = 57, 1.5%).

All patients provided informed consent. Data were collected and

Cohort description

The mean age was 60 years (SD = 7.1) and median PSA was 5.2 ng/ml (interquartile range: 4.1–7.2; Table 1). Following surgery, Gleason score 6 was identified in 1,088 (31%), Gleason 7 in 2,213 (62%), Gleason 8 in 131 (4%), and Gleason 9 in 124 (3%). Pathologic stage was pT2a in 320 (9%), pT2b in 304 (9%), pT2c in 2,099 (57%), pT3a in 728 (20%), and pT3b in 193 (5%). PSM was identified in 672 (18.9%). PSM rates by pathologist varied from 8.3% to 27.5% (Fig. 1). Among the 29 pathologists examined,

Discussion

We demonstrate that the individual pathologist’s experience is independently associated with the rate of PSMs following RP. There appears to be a learning curve among pathologists for identifying PSMs with increasing odds of finding PSMs as experience is accrued. The relationship was most pronounced for the pathologists with the greatest caseload.

These findings illustrate that surgical margin status can be significantly influenced by individual pathologists. Strategies to standardize the

Conclusion

We demonstrate that pathologist’s experience is an independent factor for PSM, even when controlling for fellowship training, surgeon experience, pathologic stage, Gleason score, PSA, and BMI. Based on these findings, pathologists with less experience reviewing RP specimens may consider requesting rereview by a dedicated GU pathologist.

Ethical approval

All procedures performed in these studies involving human participants were in accordance with the ethical standards of the institutional or national research committee or both, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

Authors contributions

J.E. Tallman: protocol/project development, data collection or management, data analysis, and manuscript writing/editing.

V.T. Packiam: protocol/project development, data collection or management, data analysis, and manuscript writing/editing.

K.E. Wroblewski: data collection or management, data analysis, and manuscript writing/editing.

G.P. Paner: data collection or management, data analysis, and manuscript writing/editing.

S.E. Eggener: protocol/project development, data collection or management,

Acknowledgments

This study was supported in part by the National Institute of Diabetes, Digestive, and Kidney Diseases, United States, Grant no. 5T35DK062719-28 and in part by National Institutes of Health, United States CTSA, Grant no. UL1 TR000430.

References (33)

Cited by (7)

  • “Real-time” Assessment of Surgical Margins During Radical Prostatectomy: State-of-the-Art

    2020, Clinical Genitourinary Cancer
    Citation Excerpt :

    The high inter-observer variability in the assessment of surgical margins (SMs) between pathologists during RP (κ = 0.45) is among the main factors causing this controversy.7,8 Furthermore, the PSM rate is greatly affected by the experience of the surgeons and pathologists, which in turn, can result in highly variable rates of PSMs between different studies.9 Thus, the International Society of Urological Pathology (ISUP) published their recommendation about SM assessment to standardize the pathologic reporting of SM status.10

  • Impact of Multifocality and Multilocation of Positive Surgical Margin After Radical Prostatectomy on Predicting Oncological Outcome

    2019, Clinical Genitourinary Cancer
    Citation Excerpt :

    Recently, a close surgical margin, defined as cancer cells coming within 0.1 mm from surgical margin, was also found to increase the BCR rate significantly when compared with pure negative surgical margin.3 Risk factors for PSM included PSA level, GS, tumor volume, pT stage, surgical approach, and the surgeon's experience, as well as the pathologist's interpretation.4-8 Previously, extensive discussions on PSM have been mainly focused on its location, number, length, and GS.4,5

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Dr. Paner receives textbook publication royalties from Amirsys, Inc. Dr. Eggener’s work is funded by the NIH. The remaining authors declare that they have no conflict of interest.

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