Surgeon Experience is Strongly Associated With Biochemical Recurrence After Radical Prostatectomy for All Preoperative Risk Categories

Article Outline

• Abstract
• Methods
  • Patients and Outcomes
  • Statistical Methods
• Results
• Discussion
• Conclusions
• References
• Copyright

Purpose

We have previously reported that there is a learning curve for open radical prostatectomy. In the current study we determined whether the effects of the learning curve are modified by patient risk, as defined by preoperative tumor characteristics.

Materials and Methods

The study included 7,683 eligible patients with prostate cancer treated with open radical prostatectomy by 1 of 72 surgeons. Surgeon experience was coded as the total prior number of radical prostatectomies done by the surgeon before a patient surgery. Multivariate survival time regression models were used to evaluate the association between surgeon experience and biochemical recurrence separately in each preoperative risk group.

Results

We saw no evidence that patient risk affected the learning curve. There was a statistically significant association between biochemical recurrence and surgeon experience on all analyses. The absolute risk difference in a patient receiving treatment from a surgeon with 10 vs 250 prior radical prostatectomies was 6.6% (95% CI 3.4–10.3), 12.0% (95% CI 6.9–18.2) and 9.7% (95% CI 1.2–18.2) in patients at low, medium and high preoperative risk. Recurrence-free probability in patients with low risk disease approached 100% for the most experienced surgeons.

Conclusions

Cancer control after radical prostatectomy improves with increasing surgeon experience irrespective of patient risk. Excellent rates of cancer control in patients with low risk disease treated by the most experienced surgeons suggest that the primary reason that recurrence develops in such patients is inadequate surgical technique. The results have significant implications for clinical care.

Key Words: prostate, prostatectomy, prostatic neoplasms, practice (psychology), outcome assessment (health care)

Abbreviations and Acronyms: PSA, prostate specific antigen

Radical prostatectomy is a technically challenging operation with outcomes that depend in part on surgical experience. For example, prior reports have shown that the patients of higher volume surgeons have shorter hospital stays, fewer perioperative complications, fewer anastomotic strictures and better urinary continence rates.¹, ², ³ Furthermore, these studies showed that surgeons who had the best results for 1 outcome measure also performed better in other measures, the variation among surgeons in the rate of complications was significantly greater than expected by chance and outcomes were independent of hospital volume.¹, ², ³

Other studies have shown that the effects of surgical experience on outcome are not restricted to postoperative complications. For example, surgeon volume has been found to be associated with overall survival after rectal cancer resection, although 30-day mortality was no different between high and low volume surgeons.⁴ We recently reported a similar finding for radical prostatectomy, observing that the lifetime experience of the surgeon with this procedure is strongly associated with the likelihood of biochemical failure that persists even after adjusting for case mix.⁵ In a typical patient we estimated a 5-year probability of biochemical recurrence of 17.9% when surgery was performed by an inexperienced surgeon (10 prior cases), compared to 10.7% when performed by a more experienced surgeon (250 prior cases).

In this study we determined whether the learning curve for radical prostatectomy differs depending on preoperative patient risk, as defined by pretreatment tumor characteristics. This question is important because the choice of surgeon is perhaps the only patient modifiable factor in determining outcome. The current study differs from our prior work, in that in the previously performed analysis risk groups were defined postoperatively by pathological stage rather than by preoperative factors.

Specifically we asked whether surgeon experience is important in all patients or whether experience has an important impact on outcome only in certain subgroups, such as those at highest risk for failure. In this analysis we considered the hypotheses that surgeon technique affects only favorable risk tumors, perhaps because recurrence of locally advanced disease is related to tumor cells that have spread before surgery, or only unfavorable disease on the ground that tumors with favorable pretreatment features are at low risk for recurrence.

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Methods 

Patients and Outcomes 

The study cohort consisted of 9,376 patients with clinically localized prostate cancer who were treated with open radical retropubic prostatectomy between January 1987 and December 2003 at 1 of 4 participating institutions, including Memorial Sloan-Kettering Cancer Center, New York, New York; Baylor College of Medicine, Houston, Texas; Wayne State University, Detroit, Michigan; and Cleveland Clinic, Cleveland, Ohio. Patients receiving neoadjuvant therapy (1,316) or adjuvant therapy (85), or who had missing data on surgeon (144), PSA (66) or clinical stage (82) were excluded, leaving 7,683 eligible for analysis. All information was obtained with appropriate institutional review board waivers and data were de-identified before analysis.

Patients were treated by 1 of 72 surgeons, of whom all treated patients only at the study institutions while on staff. Surgeons who performed the initial radical prostatectomy at a nonstudy institution were asked to provide their prior caseload. Cancer recurrence was defined as serum PSA more than 0.4 ng/ml, as corroborated by subsequently higher PSA, ie biochemical recurrence.⁶ In rare cases, eg fewer than 1% in the Memorial Sloan-Kettering Cancer Center data set, secondary treatment was initiated in patients who did not meet the criteria for recurrence. Such treatment was counted as an event.

Statistical Methods 

Our research question was whether more experienced surgeons had better results irrespective of patient risk or whether the association between experience and outcome would be found only in certain risk groups. For preoperative risk analysis patients were categorized into 3 risk group categories, as described by D'Amico et al based on preoperative variables, including low—PSA less than 10 ng/ml and biopsy Gleason score 6 or less with clinical stage less than T2c, high—PSA greater than 20 ng/ml, biopsy Gleason score 8 or greater, or clinical stage T2c or greater and intermediate—patient did not meet criteria for high or low risk.⁷

For each patient surgeon experience was coded as the number of radical prostatectomies done by the surgeon before the patient operation. This number reflected total prior experience, including operations performed at former institutions and in patients ineligible for analysis. We first performed exploratory analyses to see whether there were differences in surgical experience by risk group. For these analyses surgeon experience was entered as a continuous variable in a logistic regression model with clustering by surgeon.

Our main analysis was to evaluate the association between surgeon experience and recurrence after radical prostatectomy in each risk group. To do so we fitted a multivariate parametric survival time regression model using a log-logistic survival distribution to model hazard with time because followup was not independent of surgeon experience. Surgeon experience was entered as a continuous variable. Since the relationship between experience and outcome could be nonlinear, we used restricted cubic splines with knots at the quartiles. We adjusted for within-surgeon clustering using a generalized estimating equations approach⁸ by specifying the cluster option in Stata® 9.2. Because few patients died before experiencing recurrence (5-year overall survival probability 95%), we did not adjust for competing risk and censored patients at the date of death.

We originally intended to use year of surgery as a covariate. However, when first fitting our statistical model to predict recurrence by surgical experience, we observed some implausible results in patients at high preoperative risk. The learning curve increased up to approximately 500 prior cases and then it started to decrease, such that highly experienced surgeons appeared to have results comparable to those of surgeons treating their first case. On analysis this appeared to be due to our inclusion of year of surgery as a covariate. The learning curve did not decline if we removed year of surgery as a covariate or we restricted analysis to patients treated after 1995 with and without year of surgery, when the stage shift in this cohort appeared to be complete.⁵ Accordingly we believe that the apparent decline in the learning curve was a statistical artifact caused by the high correlation between year of surgery and surgeon experience coupled with the limited number of patients at high risk treated by the surgeons with the greatest levels of experience. The learning curves for patients at low and moderate risk were unaffected by the inclusion or otherwise of year of surgery as a covariate whether or not the sample was restricted to patients treated after 1995. Therefore, all results presented are without adjustment for the year of surgery.

To produce a learning curve for each subgroup of patients we calculated the 5-year recurrence-free probability predicted by the model for each level of surgical experience using the mean value for covariates in that subgroup. The CIs for the difference in 5-year recurrence rates for 10 vs 250 prior cases were determined using bootstrap methods with 1,000 replications. Prespecified sensitivity analysis was to repeat all analyses in the subgroup of patients treated after 1995, after which stage migration seemed to be largely complete.⁵, ⁹

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Results 

Table 1 lists clinical and pathological patient characteristics. Based on preoperative tumor characteristics 3,422 patients (45%) were categorized as at low risk, 2,527 (33%) were categorized as at intermediate risk and 1,734 (23%) were categorized as at high risk. For preoperative risk there was a moderate but statistically significant negative association between risk group and surgeon experience (p = 0.011). These results appeared to be due to stage migration. There was no statistically significant association between surgeon experience and preoperative risk when analysis was restricted to patients treated after 1995 (p = 0.2).

Table 1. Clinical and pathological patient characteristics by preoperative risk category

	Low Risk	Intermediate Risk	High Risk
No. pts	3,422	2,527	1,734
Mean age at surgery (interquartile range)	60 (55–65)	62 (57–66)	63 (58–67)
Mean ng/ml total PSA (interquartile range)	5.7 (4.4–7.0)	8.4 (5.6–12.0)	10.6 (6.0–22.8)
No. clinical stage (%):
T1	2,279 (67)	1,124 (44)	268 (15)
T2a	1,143 (33)	794 (31)	234 (13)
T2b	0	609 (24)	175 (10)
T2c/T3/T4	0	0	1057 (61)
No. biopsy Gleason score (%):
6 or Less	3,422 (100)	1,012 (40)	831 (48)
7	0	1,515 (60)	489 (28)
8 or Greater	0	0	414 (24)
No. pathology Gleason score (%):
5 or Less	242 (7)	99 (4)	87 (5)
6	1,906 (56)	677 (27)	414 (24)
7	1,235 (36)	1,603 (63)	924 (53)
8	32 (1)	116 (5)	198 (11)
9 or Greater	7 (0)	32 (1)	111 (6)
No. extracapsular extension (%)	524 (15)	875 (35)	840 (48)
No. seminal vesicle invasion (%)	52 (2)	270 (11)	368 (21)
No. lymph node metastasis (%)	22 (1)	82 (3)	184 (11)
No. surgeon experience (%):
0–49 Cases	570 (17)	494 (20)	327 (19)
50–99 Cases	296 (9)	239 (9)	160 (9)
100–249 Cases	594 (17)	518 (20)	439 (25)
250–999 Cases	1,336 (39)	938 (37)	624 (36)
1,000 Cases or greater	626 (18)	338 (13)	184 (11)
No. pos surgical margins or greater (%)	670 (20)	745 (29)	633 (37)

Low—PSA less than 10 ng/ml and biopsy Gleason score 6 or less with clinical stage T2a or less, intermediate—does not meet criteria for high or low risk and high—PSA greater than 20 ng/ml, clinical stage T2c or greater, or biopsy Gleason score 8 or greater.

There were 1,253 recurrences. Median followup in recurrence-free patients was 4.0 years. The figure shows the learning curve for cancer control after radical prostatectomy, stratified by preoperative risk group. Table 2 illustrates the learning curve by showing the adjusted 5-year recurrence-free probability in a patient treated by a surgeon with 10 and 250 prior cases. Surgeon experience was significantly associated with outcome in the low, intermediate and high risk groups (p <0.001, <0.001 and 0.016, respectively). Moreover, the risk difference between more and less experienced surgeons was clinically relevant for all risk categories. Low and intermediate risk group curves continued to increase after 1,000 completed cases, suggesting that surgeons continued to improve even after they were considered to be highly experienced.

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• Learning curve for cancer control after radical prostatectomy stratified by preoperative risk group shows predicted probability of freedom from biochemical recurrence (BCR) at 5 years with increasing surgeon experience in patient with typical cancer severity in risk group (mean PSA, pathological stage and grade) per group. Light gray curves indicate low risk. Medium gray curves indicate intermediate risk. Black curves indicate high risk. Dotted curves indicate 95% CI.

Table 2. Effects of surgeon experience on outcome by preoperative risk group and in 5,038 patients treated after 1995

Risk Analysis	Surgeon Experience Adjusted p Value	Adjusted % 5-Yr Recurrence Probability		10 vs 250 Prior Case Difference (95% CI)
		10 Prior Cases	250 Prior Cases	% Absolute	Relative
Overall:
Low	<0.001	11.0	4.4	6.6 (3.4–10.3)	2.5 (1.7–4.0)
Intermediate	<0.001	25.4	13.4	12.0 (6.9–18.2)	1.9 (1.5–2.6)
High	0.016	42.6	32.9	9.7 (1.2–18.2)	1.3 (1.03–1.6)
After 1995:
Low	0.008	10.3	2.2	8.1 (2.7–12.8)	4.7 (2.2–11.8)
Intermediate	<0.001	27.1	10.4	16.7 (7.6–25.1)	2.6 (1.7–4.3)
High	0.001	46.3	19.5	26.8 (11.6–43.4)	2.4 (1.5–3.8)

Probabilities are in patient with typical cancer severity in each group (mean PSA, stage and grade) treated at series mid point.

Table 2 also shows the results of sensitivity analysis restricted to patients treated after 1995, when stage migration in our cohort appeared largely complete. These results confirmed our main findings that surgeon experience had clinically relevant effects irrespective of risk group. The learning curves for each risk group were also similar (data not shown). In particular the 5-year recurrence-free probability was greater than 98% for a patient with low risk disease treated by a surgeon with the greatest levels of experience.

As an additional sensitivity analysis, we used tertiles of the Kattan preoperative nomogram¹⁰ to define risk groups. Five-year recurrence-free survival probabilities were 93.4% to 98.3%, 87.2% to 93.3% and less than 87.2% in the low, intermediate and high risk groups, respectively. Surgeon experience was associated with biochemical recurrence in the low, intermediate and high risk groups (p = 0.002, <0.001 and 0.002, respectively). Absolute differences in recurrence probabilities between patients treated by surgeons with 10 and 250 cases were similar to main analysis results (7.0%, 9.9% and 9.9%, respectively).

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Discussion 

We found that cancer control after radical prostatectomy improves with increasing surgeon experience irrespective of preoperative risk group. In the overall cohort the absolute decrease in the risk of recurrence at 5 years in a patient seeing an experienced rather than an inexperienced surgeon varied between 6.6% and 12% depending on risk group (table 2). These differences increased in patients treated after 1995 (table 2), further emphasizing the clinical relevance of surgeon experience in the PSA era. We found no evidence that it is only high risk cases that may need to be treated by highly experienced surgeons. Thus, we can state that the best chance for cure rests in the most experienced hands in patients in all risk groups.

These findings corroborate prior studies showing associations between the surgeon yearly caseload and decreased perioperative mortality,¹¹ lower rates of surgical complications¹, ², ³ and improved overall survival.⁴ The findings support calls for the regionalization of prostate cancer care at centers of excellence,¹² as recommended by the National Health Service in the United Kingdom.¹³ Learning curves in patients with low risk disease asymptoted toward 0% recurrence with increasing surgeon experience. Conversely the learning curve for high risk disease flattened at an approximately 70% recurrence-free probability at 5 years, suggesting that about a third of these patients cannot be cured by surgery alone.

These findings have important implications for clinical care. Specifically if a sufficiently experienced surgeon is able to cure all or almost all patients with low risk disease, the obvious corollary is that recurrence in these patients is primarily a matter of surgical technique. Such a conclusion supports the need for research and changes in surgical education. It is currently unclear exactly what surgical steps the most experienced surgeons use to avoid recurrence. Our findings make it clear that systematic research is required to identify the critical aspects of radical prostatectomy that are associated with cancer control. These findings also suggest a need to expand opportunities for training in surgical technique for surgeons in the early years after residency training, encourage less experienced surgeons to look at their results and obtain additional training and determine whether surgical simulators and minimally invasive tools such as robots can shorten the learning curve. It is also clear from these results that surgical experience should be added to nomograms that predict the likelihood of cure based on pretreatment parameters.

The observed flattening of the learning curve in patients in the high risk group suggests that surgery alone in not able to cure approximately a third of those in this group. This most likely reflects that a subset of patients with the most unfavorable tumor characteristics have cancer outside the immediate confines of the prostate and their chance for cure is not determined by therapy directed at the primary tumor. It is clear that these patients require a multimodality approach to treatment with the best combination and sequencing of available modalities, including surgery, radiation and systemic therapies yet to be determined.

A possible limitation of our study is that the model was based on patients treated at major academic centers. It is not clear that our results pertain to surgeons practicing in other settings. For example, surgeons in our cohort may have had steeper learning curves than those in solo practice in the community because they had protected research time, worked in a competitive environment that promotes criticism and self-evaluation, and were constantly exposed to new ideas and techniques.

Moreover, one of our findings, that recurrence rates for low risk cancers tended toward zero with increasing surgical experience, was based on a limited number of surgeons. Only 2 surgeons in our series treated more than 1,000 cases. We do not believe that this materially affected our conclusions on the grounds that, even if only 1 surgeon could achieve near-zero recurrence rates, recurrence must have been due to inadequate surgical technique. However, caution is advised when applying these results to other surgeons. It seems plausible that outcomes may differ between 2 surgeons with similar levels of experience. As such, it may not be the case that all highly experienced surgeons have uniformly excellent results with low risk disease.

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Conclusions 

The surgical learning curve for radical prostatectomy is relevant in all patients irrespective of preoperative risk. Recurrence rates were close to zero in patients with low risk disease treated by the most experienced surgeons in our data set, suggesting that the primary reason that recurrence develops in such patients is inadequate surgical technique.

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References 

1. Hu JC, Gold KF, Pashos CL, Mehta SS, Litwin MS. Role of surgeon volume in radical prostatectomy outcomes. J Clin Oncol. 2003;21:401
   • View In Article
   • MEDLINE
   • CrossRef
2. Bianco FJ, Riedel ER, Begg CB, Kattan MW, Scardino PT. Variations among high volume surgeons in the rate of complications after radical prostatectomy: further evidence that technique matters. J Urol. 2005;173:2099
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (340 KB)
   • CrossRef
3. Begg CB, Riedel ER, Bach PB, Kattan MW, Schrag D, Warren JL, et al. Variations in morbidity after radical prostatectomy. N Engl J Med. 2002;346:1138
   • View In Article
   • CrossRef
4. Schrag D, Panageas KS, Riedel E, Cramer LD, Guillem JG, Bach PB, et al. Hospital and surgeon procedure volume as predictors of outcome following rectal cancer resection. Ann Surg. 2002;236:583
   • View In Article
   • MEDLINE
   • CrossRef
5. Vickers AJ, Bianco FJ, Serio AM, Eastham JA, Schrag D, Klein EA, et al. The surgical learning curve for prostate cancer control after radical prostatectomy. J Natl Cancer Inst. 2007;99:1171
   • View In Article
   • CrossRef
6. Stephenson AJ, Kattan MW, Eastham JA, Dotan ZA, Bianco FJ, Lilja H, et al. Defining biochemical recurrence of prostate cancer after radical prostatectomy: a proposal for a standardized definition. J Clin Oncol. 2006;24:3973
   • View In Article
7. D'Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA, et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. J Am Med Ass. 1998;280:969
   • View In Article
8. Lee EWLJ, Wei D, Amato D. Cox-type regression analysis for large number of small groups of correlated failure time observations. In:  Klein JP,  Goel PK editor. Survival Analysis: State of the Art 1992. Dordecht: Kluwer Academic; 1992;p. 237–247
   • View In Article
9. Dong F, Reuther AM, Magi-Galluzzi C, Zhou M, Kupelian PA, Klein EA. Pathological stage migration has slowed in the late PSA era. Urology. 2007;70:839
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (114 KB)
   • CrossRef
10. Stephenson AJ, Scardino PT, Eastham JA, Bianco FJ, Dotan ZA, Fearn PA, et al. Preoperative nomogram predicting the 10-year probability of prostate cancer recurrence after radical prostatectomy. J Natl Cancer Inst. 2007;98:715
    • View In Article
    • CrossRef
11. Birkmeyer JD, Stukel TA, Siewers AE, Goodney PP, Wennberg DE, Lucas FL. Surgeon volume and operative mortality in the United States. N Engl J Med. 2003;349:2117
    • View In Article
    • CrossRef
12. Lipscomb J. Transcending the volume-outcome relationship in cancer care. J Natl Cancer. 2006;98:151
    • View In Article
13. Making Progress on Prostate Cancer, report of the National Health Service, November 2004. Available at http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_4093866. Accessed September 1, 2007.
    • View In Article