Risk Stratification for Biochemical Recurrence in Men With Positive Surgical Margins or Extracapsular Disease After Radical Prostatectomy: Results From the SEARCH Database

Article Outline

• Abstract
• Methods
  • Study Population
  • Statistical Analysis
• Results
• Discussion
• Conclusions
• References
• Copyright

Purpose

In men with extracapsular disease or positive surgical margins after radical prostatectomy immediate adjuvant therapy decreases the risk of biochemical recurrence at the cost of increased toxicity. We further stratified these men into a low risk group in which watchful waiting after surgery may be preferred and a high risk cohort in which adjuvant therapy may be preferred.

Materials and Methods

We performed a retrospective analysis of the records of 902 men treated with radical prostatectomy in the Shared Equal-Access Regional Cancer Hospital (SEARCH) database between 1988 and 2007 with positive surgical margins and/or extracapsular disease without seminal vesicle invasion or lymph node metastasis. The significant independent predictors of biochemical recurrence were determined using a multivariate Cox proportional hazards model. Based on the recurrence risk generated from the multivariate Cox proportional hazards regression model we generated tables to estimate the risk of recurrence-free survival 1, 3 and 5 years after surgery.

Results

At a median of 3 years of followup 346 patients (39%) had biochemical recurrence. On multivariate analysis the significant predictors of biochemical recurrence were age more than 60 years, prostate specific antigen more than 10 ng/ml, Gleason score 4 + 3 and 8–10, 2 or more sites of positive surgical margins and prostate specimen weight 30 gm or less. As determined by the concordance index, the overall predictive accuracy of the model was 0.67, while it was 0.60 for the postoperative Kattan nomogram in this patient population.

Conclusions

We have developed a simple instrument that, once validated, may aid in the postoperative decision making process for men at intermediate risk for recurrence after prostatectomy.

Key Words: prostate, prostatic neoplasms, prostatectomy, prostate-specific antigen, risk

Abbreviations and Acronyms: ECE, extracapsular extension, PSA, prostate specific antigen, RT, radiation therapy, SEARCH, Shared Equal-Access Regional Cancer Hospital, SVI, seminal vesicle invasion

The number of new cases of prostate cancer projected for 2007 was 218,890, accounting for almost a third of all cancers in men excluding skin cancer. Radical prostatectomy is one of the most accepted and widely practiced management strategies for localized prostate cancer. Although the prostate cancer survival rate continues to be exceptionally good in comparison to that of other cancers, biochemical recurrence develops in up to 30% of all men undergoing surgical treatment.¹, ² It is acknowledged that cases of organ confined cancer are least likely to recur, while those of SVI or lymph node metastases are at highest risk for recurrence.³ It seems intuitive that men with organ confined disease would benefit most from a watchful waiting approach, while prior studies have shown that early aggressive treatment in the latter group improves overall survival, at least in those with lymph node involvement.⁴ However, in men at intermediate risk, that is those with a positive surgical margin or ECE without SVI, optimal treatment remains unclear.

Recently 2 large, prospective clinical trials investigated the role of immediate adjuvant RT in men with extracapsular disease or a positive surgical margin following radical prostatectomy.⁵, ⁶ The 2 studies showed that adjuvant therapy decreased the risk of PSA recurrence but at the cost of increased toxicity. While no metastasis-free or overall survival benefit was seen in either study, it is unknown whether this represents a lack of true long-term benefit from adjuvant treatment or a function of modest patient numbers without sufficient followup. Ultimately balancing the benefit of decreased biochemical recurrence must be weighed against the potential for decrements in quality of life. Therefore, of men with extracapsular disease or a positive surgical margin we identified patients at low risk for recurrence in whom close observation may be the preferred treatment approach, while also identifying those at high risk and in whom adjuvant therapy may be warranted. To accomplish this we used the multicenter, multi-ethnic SEARCH Database of men treated with radical prostatectomy at multiple Veterans Affairs Medical Centers across the United States.

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Methods 

Study Population 

After obtaining institutional review board approval from each institution to abstract and combine data we combined data on patients undergoing radical prostatectomy at the Veterans Affairs Medical Centers in West Los Angeles, Palo Alto, San Francisco, Augusta and Durham into the SEARCH database.⁷ This database includes information on patient age at surgery, race, height, weight, clinical stage, cancer grade on diagnostic biopsies, preoperative PSA, surgical specimen pathology (specimen weight, tumor grade, stage and surgical margin status) and followup PSA. Patients treated with preoperative androgen deprivation or RT were excluded. Of the 2,062 men in the SEARCH Database we excluded 32 and 205 who were at high risk for recurrence due to lymph node metastasis and SVI, respectively. Due to the low risk of recurrence we excluded men with organ confined disease and negative margins. This resulted in a study population of 902 men.

Biochemical recurrence was defined as a single PSA of greater than 0.2 ng/ml, 2 concentrations at 0.2 ng/ml or secondary treatment for increased postoperative PSA. Prostatectomy specimens were sectioned according to the protocol at each institution.⁷ Margins were categorized as positive or negative at each given anatomical location, ie the apex, bladder neck, left periphery or right periphery. Information on the number of positive foci at each location was not available and, thus, cases were defined as positive or negative at each location. The number of positive margins was calculated by adding the number of locations with a positive margin. Each location was considered mutually exclusive. For example, a man with an isolated left apical margin was considered to have a positive apical margin but not a left lateral margin for a total of 1 positive margin.

Statistical Analysis 

Significant risk factors for time to biochemical recurrence were examined using log rank survivorship analysis and Cox proportional hazards regression. The variables considered for entry into the model were patient age, race, body mass index, year of surgery, SEARCH site, preoperative serum PSA, pathological Gleason score, ECE, number of positive surgical margins and prostate specimen weight. Because our goal was to develop tables that would be easy to use, this necessitated identifying cutoff points to categorize the significant prognostic characteristics. Therefore, we performed univariate exploratory analysis of the identified significant variables using multiple clinically relevant cutoff points for each variable, eg age 50 years or younger vs older than 50 and 60 years or younger vs older than 60, etc. We determined that grouping age 60 years or younger vs older than 60, Gleason score 3 + 4 or less, 4 + 3 vs 8–10, preoperative PSA 10 ng/ml or less vs more than 10, prostate specimen weight 30 gm or less vs more than 30 and the number of positive margin locations 2 or fewer vs greater than 2 provided the maximum likelihood chi-square ratio for estimating time to biochemical recurrence. Therefore, these groupings were used in the multivariate model. For multivariate analysis a stepwise Cox proportional hazards model was used with p <0.15 to determine which variables should be entered into the model at each step. The variable with the highest p value was then successively deleted until only variables with p <0.1 remained. The predictive performance of the model was assessed and compared with that of the postoperative Kattan nomogram⁸ using the concordance index.⁹ Tables were generated to predict the 1, 3 and 5-year actuarial risk of biochemical recurrence-free survival using the coefficients of the multivariable Cox model. All statistical analysis was performed using STATA® 9.2 or SAS® 9.1.3 with p <0.05 considered statistically significant.

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Results 

Table 1 lists patient demographic and clinicopathological characteristics. Of the patients 554 (61%) were younger than 60 years, 586 (65%) had preoperative PSA 10 ng/ml or less and 760 (87%) had a pathological Gleason score of 7 or less. Of the men 358 (40%) were black. In men without recurrence mean ± SD followup was 4.0 ± 3.6 years (median 3.0). Overall 346 patients (39%) experienced biochemical recurrence (see figure). The 1, 3 and 5-year overall risk of biochemical recurrence was 19%, 34% and 48%.

Table 1. Preoperative clinical and pathological characteristics in men in SEARCH database with positive surgical margin or ECE

Characteristics
No. pts	902
Mean±SD age at surgery	62.0±6.6
Preop PSA(ng/ml)
Mean±SD	10.5±11.0
Median(range)	7.5(0.56–140)
No. race(%):
White	493(55)
Black	358(40)
Other	45(5)
No. clinical stage(%):
T1	422(52)
T2	379(47)
T3	5(1)
No. biopsy Gleason score(%):
2–6	526(60)
3 + 4	208(24)
4 + 3	69(8)
8–10	68(8)
No. pathological stage(%):
pT2, pos margin	514(57)
pT3, neg margin	144(16)
pT3, pos margin	244(27)
No. pathological Gleason score:
2–6	283(32)
3 + 4	384(44)
4 + 3	93(11)
8–10	114(13)
Prostate specimen wt,(gm):
Mean±SD	40.9±20.0
Median(range)	36.7(8.2–232.5)
No. lymph node status (%):
Neg	643(71)
Unknown	259(29)

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• Actuarial 10-year Kaplan-Meier estimates of biochemical recurrence rates in patients.

On univariate exploratory analysis the number of positive surgical margins, pathological Gleason score and preoperative serum PSA were significantly associated with biochemical relapse (each p <0.001), as was prostate specimen weight (p = 0.002) and age at surgery (p = 0.03). No other variables were significantly associated with time to biochemical recurrence. On multivariate analysis, similar to univariate analysis, only age at surgery, pathological Gleason score, number of positive margins, PSA and prostate weight were significantly predictive of biochemical recurrence (table 2). As defined by the concordance index, the overall accuracy of this multivariate model to predict biochemical recurrence was 0.67. This compared favorably with the postoperative Kattan nomogram,⁸ which had a concordance index of 0.60 in our subset of patients.

Table 2. Multivariate Cox proportional hazards analysis of factors estimating time to biochemical recurrence following radical prostatectomy

Variables	HR(95% CI)	Coefficient β	p Value
Pt age older than 60 vs 60 or younger	1.57(1.17–2.11)	0.45	0.003
Preop PSA greater than 10 vs 10 ng/ml or less	1.59(1.21–2.09)	0.46	0.001
Pathological Gleason score(vs 3 + 4 or less):
4 + 3	1.57(1.06–2.32)	0.45	0.025
8–10	2.17(1.51–3.10)	0.77	<0.001
No. pos margins(greater than 2 vs 2 or less)	1.96(1.49–2.57)	0.67	<0.001
Prostate wt (30 or less vs greater than 30 gm)	1.72(1.29–2.30)	0.55	<0.001

We used the significant risk factors identified in table 2 to generate tables to estimate the risk of biochemical recurrence-free survival 1, 3 and 5 years after surgery (table 3). For example, the 1, 3 and 5-year risk of biochemical recurrence-free survival in a man 60 years or younger with preoperative serum PSA 10 ng/ml or less, pathological Gleason score 3 + 4 or lower, 2 or fewer positive margins and a prostate specimen weight of greater than 30 gm was 93%, 87% and 79%, respectively. This compared to a 1, 3 and 5-year risk of PSA recurrence-free survival of 26%, 7% and 1%, respectively, in a man older than 60 years with preoperative serum PSA more than 10 ng/ml, pathological Gleason score 8 through 10, greater than 2 positive margins and a prostate specimen weight of 30 gm or less.

Table 3. Estimated risk of biochemical recurrence-free survival after prostatectomy

PSA(Gleason score)	2 or Fewer Pos Margins % Risk Estimate(95% CI)		Greater Than 2 Pos Margins % Risk Estimate(95% CI)
	Prostate Wt Greater Than 30 gm	Prostate Wt 30 gm or Less	Prostate Wt Greater Than 30 gm	Prostate Wt 30 gm or Less
Yr 1, age 60 or younger
10 or Less ng/ml:
3 + 4 or Less	93(91–95)	88(84–92)	87(82–91)	78(72–86)
4 + 3	89(84–94)	82(75–91)	80(72–89)	68(56–82)
8–10	85(79–92)	76(67–87)	74(64–85)	59(46–75)
Greater than 10 ng/ml:
3 + 4 or Less	89(85–93)	82(76–89)	80(73–87)	68(58–79)
4 + 3	83(76–91)	73(62–86)	70(59–83)	54(40–74)
8–10	78(69–88)	65(53–80)	61(49–77)	43(29–63)
Yr 1, age older than 60
10 or Less ng/ml:
3 + 4 or Less	89(86–92)	82(77–88)	80(74–86)	68(59–78)
4 + 3	84(78–90)	74(64–85)	71(60–83)	55(41–73)
8–10	78(71–86)	65(54–78)	62(50–76)	43(30–63)
Greater than 10 ng/ml:
3 + 4 or Less	83(79–88)	73(65–82)	70(62–79)	54(43–69)
4 + 3	75(67–85)	61(48–78)	57(45–73)	38(24–61)
8–10	68(58–79)	51(38–69)	46(34–63)	27(15–48)
Yr 3, age 60 or younger
10 or Less ng/ml:
3 + 4 or Less	87(83–91)	78(72–85)	76(68–83)	62(52–73)
4 + 3	80(72–89)	68(56–82)	64(52–80)	46(32–68)
8–10	73(63–85)	59(46–75)	54(41–72)	35(22–56)
Greater than 10 ng/ml:
3 + 4 or Less	80(73–87)	67(58–79)	64(54–75)	47(34–62)
4 + 3	70(59–83)	54(40–74)	50(36–69)	30(17–54)
8–10	61(49–76)	43(28–64)	38(25–58)	19(9–40)
Yr 3, age older than 60
10 ng/ml or Less:
3 + 4 or Less	80(75–85)	68(60–77)	64(56–74)	47(36–61)
4 + 3	70(61–81)	54(41–72)	50(37–68)	30(17–54)
8–10	61(51–74)	43(30–61)	38(26–57)	19(9–39)
Greater than 10 ng/ml:
3 + 4 or Less	70(63–78)	54(43–68)	50(39–62)	30(19–48)
4 + 3	57(45–72)	38(24–60)	33(21–53)	15(6–37)
8–10	46(34–62)	26(15–47)	22(12–39)	7(2–23)
Yr 5, age 60 or younger
10 ng/ml or Less:
3 + 4 or Less	79(74–86)	67(59–77)	64(54–74)	46(35–60)
4 + 3	70(58–83)	54(40–73)	49(35–69)	30(16–54)
8–10	61(48–76)	42(28–63)	38(24–59)	18(9–40)
Greater than 10 ng/ml:
3 + 4 or Less	69(61–79)	53(42–68)	49(38–63)	29(18–47)
4 + 3	56(43–74)	37(22–61)	32(19–55)	14(5–38)
8–10	45(31–65)	25(13–49)	21(10–42)	7(2–23)
Yr 5, age older than 60
10 ng/ml or Less:
3 + 4 or Less	70(63–76)	53(44–65)	49(40–61)	29(19–45)
4 + 3	57(45–71)	38(24–59)	33(20–54)	15(6–37)
8–10	45(33–62)	26(15–46)	21(11–40)	7(2–22)
Greater than 10 ng/ml:
3 + 4 or Less	56(48–66)	37(26–53)	32(22–46)	14(7–30)
4 + 3	40(28–58)	21(10–44)	17(8–36)	5(1–21)
8–10	29(18–46)	12(4–30)	9(3–23)	1(lessthan1–9)

How this should be explained to a patient is that, Mr. X, given your PSA, age, prostate weight, number of positive surgical margins and your Gleason sum, our best guess is that you have an X(actual value from the table) percent chance of not developing PSA recurrence at 1, 3 and 5 years. We are 95% confident that your chances of not recurring are somewhere between x and y (the lower and upper limits of the 95% confidence CI).

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Discussion 

Despite being one of the most effective methods for managing organ confined disease, radical prostatectomy is still plagued with a recurrence rate of 15% to 40%.¹, ² While pathological stage and grade are useful determinants of recurrence risk, many men find themselves in an intermediate risk group based on standard pathological features. In these men adjuvant radiation has been suggested as a potential modality to decrease the biochemical recurrence risk, although at the cost of increased toxicity.⁵, ⁶ To better risk stratify these men we examined patients with extracapsular disease or a positive margin after radical prostatectomy and determined significant risk factors for biochemical recurrence. Along with the standard prognostic variables of PSA and Gleason grade we found that the number of positive margins as well as prostate size and patient age were significant predictors of biochemical recurrence. Using these features we developed tables to estimate the risk of biochemical recurrence-free survival 1, 3 and 5 years after surgery. It is hoped that after these tables are validated their use may help guide men and their physicians toward identifying those with the greatest and lowest need for adjuvant therapy.

In the current study of men at intermediate risk the overall 5-year biochemical recurrence-free survival rate was 55%. Therefore, almost half of the men in this group would have recurrence by 5 years, while half would not. This is in line with prior studies showing that the risk of recurrence in men with positive surgical margins was similarly near 50%.¹⁰ This highlights the uncertain future in these men who are at high risk for recurrence.

Analogous to multiple prior studies, we found that men with higher preoperative PSA and higher grade disease were at increased risk for biochemical recurrence.¹¹, ¹² Apart from these well discussed variables we found that the number of margins was strongly associated with the risk of biochemical failure. Specifically the risk of recurrence increased in those with 2 or more positive margins, while men with 1 or 0 positive margins had similar outcomes. Across many studies positive margins have been strongly associated with recurrence¹², ¹³ but studies showing the number of margins as a risk factor for recurrence are infrequent.¹⁴, ¹⁵ Lowe and Lieberman found that men with more than 1 positive margins were at increased risk for recurrence on univariate analysis.¹⁴ However, no multivariate analysis was performed. In the current study the number of positive margins remained a significant predictor of recurrence on multivariate analysis. Our findings are similar to those of Obek et al, who found that 2 or more positive margins were associated with a 2.5 times increased risk of biochemical recurrence.¹⁵ Therefore, future studies should include not only whether the overall surgical margins are positive, but also the number of positive margins.

Several prior studies have shown that younger men tend to have more favorable clinical outcomes after radical prostatectomy.¹⁶, ¹⁷ In agreement with these prior studies, including one from the SEARCH database,¹⁷ we also found that younger men had better outcomes. Although invariably age is on a continuum, we found that a cutoff of age 60 years provided the best separation between young and old. However, in different patient populations the exact cutoff may vary. Whether age 60 years is truly the optimal cutoff remains to be determined.

We¹⁸ and others¹⁹ have previously found that men with a smaller prostate are at increased risk for recurrence. The current study lends further support to the growing literature suggesting a clinically important and statistically significant association between small prostate size and poor outcome. It has previously been suggested that much of this association may be driven by larger prostates producing more PSA from benign elements, leading to early detection and creating a lead time bias.¹⁹ However, it has also been suggested that there may be a true biological link between small prostate size and aggressive prostate cancer. If true, it is unknown whether this results from a local paracrine effect of the benign elements suppressing aggressive cancer, a small prostate creating a hostile environment in which only the most aggressive cancers can survive¹⁸ or an alternative explanation. However, regardless of the reason the clinical significance is that small prostate size appears to be associated with poorer outcomes in men with prostate cancer.

Ultimately after putting all of the significant risk factors together we derived tables to estimate the risk of recurrence-free survival 1, 3 and 5 years after surgery. The tables have the advantage of being able to estimate the risk of biochemical recurrence-free survival based on easily available clinicopathological characteristics and they do not involve complex calculations. The accuracy of these tables was 67% for predicting time to biochemical recurrence. Overall this compared well with the Kattan postoperative nomogram, which had a predictive accuracy of only 60% in our patients.⁸ However, the modest predictive accuracy of 67% highlights the difficulty in predicting outcome in men at intermediate risk. It is hoped that in the future molecular markers will be available to further aide risk stratification in this group.

Our study has several limitations. First and foremost, although our model to predict recurrence appeared to perform better than the commonly used Kattan nomogram, this was based on the same population from which our model was derived. Therefore, external validation is required to assess whether this also holds true in other populations. Also, in many subsets the CIs are wide (table 3). This likely reflects small patient numbers, but also the fact that currently available clinical and pathological information is inexact for predicting outcome. Future studies are needed to better identify molecular markers that can improve risk stratification. Followup in our patients was relatively short. Longer followup with more individuals in the higher risk categories would enable us to derive more robust conclusions. We must bear in mind that, although it is an acceptable clinical end point, biochemical recurrence is not a perfect surrogate for more concrete end points, such as metastases or cancer specific death, since biochemical recurrence has a highly variable natural history. However, early biochemical recurrence is linked with an increased risk of prostate cancer death.²⁰ The current study used noncentralized pathological evaluation of surgical specimens from multiple institutions by multiple pathologists, which may have made the pooling of pathological findings problematic. However, this may better represent what most practicing urologists can expect in their practice and, as such, it may have broader applicability than single institutional series. Finally, while our model may be able to better risk stratify patients, the amount of risk that should be the threshold to treat is difficult to determine. This decision may be influenced by a multitude of factors, including life expectancy, comorbidities and individual patient preference. Ultimately it is at the discretion of the patient and treating physician to decide on treatment options.

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Conclusions 

We have developed an device that is easy to use, which after validation in other patient populations should enable physicians and patients to assess the risk of recurrence in a subgroup of patients at intermediate risk after radical prostatectomy. This will serve to guide the decision making process, specifically regarding the need for adjuvant therapy.

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References 

1. Han M, Partin AW, Pound CR, Epstein JI, Walsh PC. Long-term biochemical disease-free and cancer-specific survival following anatomic radical retropubic prostatectomy: the 15-year Johns Hopkins experience. Urol Clin North Am. 2001;28:555
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (726 KB)
   • CrossRef
2. Roehl KA, Han M, Ramos CG, Antenor JAV, Catalona WJ. Cancer progression and survival rates following anatomical radical retropubic prostatectomy in 3,478 consecutive patients: long-term results. J Urol. 2004;172:910
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (95 KB)
   • CrossRef
3. D’Amico AV, Whittington R, Malkowicz SB, Schultz D, Schnall M, Tomaszewski JE, et al. A multivariate analysis of clinical and pathological factors that predict for prostate specific antigen failure after radical prostatectomy for prostate cancer. J Urol. 1995;154:131
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (903 KB)
   • CrossRef
4. Messing EM, Manola J, Sarosdy M, Wilding G, Crawford ED, Trump D. Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. N Engl J Med. 1999;341:1781
   • View In Article
   • MEDLINE
   • CrossRef
5. Thompson IM, Tangen CM, Paradelo J, Lucia MS, Miller G, Troyer D, et al. Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial. JAMA. 2006;296:2329
   • View In Article
   • CrossRef
6. Bolla M, van Poppel H, Collette L, van Cangh P, Vekemans K, Da Pozzo L, et al. Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911). Lancet. 2005;366:572
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (111 KB)
   • CrossRef
7. Freedland SJ, Amling CL, Dorey F, Kane CJ, Presti JC, Terris MK, et al. Race as an outcome predictor after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Urology. 2002;60:670
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (106 KB)
   • CrossRef
8. Stephenson AJ, Scardino PT, Eastham JA, Bianco FJ, Dotan ZA, DiBlasio CJ, et al. Postoperative nomogram predicting the 10-year probability of prostate cancer recurrence after radical prostatectomy. J Clin Oncol. 2005;23:7005
   • View In Article
   • MEDLINE
   • CrossRef
9. Harrell FE, Califf RM, Pryor DB, Lee KL, Rosati RA. Evaluating the yield of medical tests. JAMA. 1982;247:2543
   • View In Article
   • MEDLINE
10. Karakiewicz PI, Eastham JA, Graefen M, Cagiannos I, Stricker PD, Klein E, et al. Prognostic impact of positive surgical margins in surgically treated prostate cancer: multi-institutional assessment of 5831 patients. Urology. 2005;66:1245
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (222 KB)
    • CrossRef
11. Partin AW, Piantadosi S, Sanda MG, Epstein JI, Marshall FF, Mohler JL, et al. Selection of men at high risk for disease recurrence for experimental adjuvant therapy following radical prostatectomy. Urology. 1995;45:831
    • View In Article
    • Abstract
    • Full-Text PDF (877 KB)
    • CrossRef
12. Bauer JJ, Connelly RR, Seterhenn IA, Deausen J, Srivastava S, McLeod DG, et al. Biostatistical modeling using traditional preoperative and pathological prognostic variables in the selection of men at high risk for disease recurrence after radical prostatectomy for prostate cancer. J Urol. 1998;159:929
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (608 KB)
    • CrossRef
13. Epstein JI. Incidence and significance of positive margins in radical prostatectomy specimens. Urol Clin North Am. 1996;23:651
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (1079 KB)
    • CrossRef
14. Lowe BA, Lieberman SF. Disease recurrence and progression in untreated pathologic stage t3 prostate cancer: selecting the patient for adjuvant therapy. J Urol. 1997;158:1452
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (648 KB)
    • CrossRef
15. Obek C, Sadek S, Lai S, Civantos F, Rubinowicz D, Soloway MS. Positive surgical margins with radical retropubic prostatectomy: anatomic site-specific pathologic analysis and impact on prognosis. Urology. 1999;54:682
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (154 KB)
    • CrossRef
16. Khan MA, Han M, Partin AW, Epstein JI, Walsh PC. Long-term cancer control of radical prostatectomy in men younger than 50 years of age: update 2003. Urology. 2003;62:86
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (135 KB)
    • CrossRef
17. Freedland SJ, Presti JC, Kane CJ, Aronson WJ, Terris MK, Dorey F, et al. Do younger men have better biochemical outcomes after radical prostatectomy?. Urology. 2004;63:518
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (121 KB)
    • CrossRef
18. Freedland SJ, Isaacs WB, Platz EA, Terris MK, Aronson WJ, Amling CL, et al. Prostate size and risk of high-grade, advanced prostate cancer and biochemical progression after radical prostatectomy: a search database study. J Clin Oncol. 2005;23:7546
    • View In Article
    • MEDLINE
    • CrossRef
19. D’Amico AV, Whittington R, Malkowicz SB, Schultz D, Tomaszewski JE, Wein A. A prostate gland volume of more than 75 cm3 predicts for a favorable outcome after radical prostatectomy for localized prostate cancer. Urology. 1998;52:631
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (136 KB)
    • CrossRef
20. Freedland SJ, Humphreys EB, Mangold LA, Eisenberger M, Partin AW. Time to prostate specific antigen recurrence after radical prostatectomy and risk of prostate cancer specific mortality. J Urol. 2006;176:1404
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (125 KB)
    • CrossRef