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Role of Androgen Deprivation Therapy in Early Salvage Radiation Among Patients With Prostate-Specific Antigen Level of 0.5 or Less

Clinical Genitourinary Cancer, 1, 13, pages e1 - e6

Comment from Henk van der Poel:  PSA progression is delayed at a median follow-up of 5 years after salvage radiotherapy for low-PSA (>0.5) recurrence after prostatectomy. Clinical metastases were shown to occur at a median of at least 7 years after prostatectomy (Pound et al.). A longer follow-up is needed, including toxicity analyses of long term follow-up before adding hormones to salvage radiotherapy routinely.

Micro-Abstract

In this study, we examine the benefit of adding androgen deprivation therapy (ADT) to salvage radiotherapy in modern patients followed with ultrasensitive prostate-specific antigen (PSA). In these 108 patients who received radical prostatectomy and salvage radiation at a PSA of 0.5 or less, we found that ADT was associated with a decreased risk of recurrence. This benefit appeared limited to men with negative margins, which suggests that men with positive margins and PSA ≤ 0.5 may be good candidates for salvage radiation alone.

Abstract

Background

The Radiation Therapy Oncology Group 96-01 randomized trial demonstrated the benefit of adding androgen deprivation therapy (ADT) to salvage radiotherapy for an increasing prostate-specific antigen (PSA) after prostatectomy, but it is unknown whether modern patients followed with ultrasensitive PSA and salvaged at a low PSA (ie, ≤ 0.5) also benefit from ADT.

Patients and Methods

The cohort comprised 108 patients who received radical prostatectomy (RP), were followed by ultrasensitive PSA, and received salvage radiotherapy at a PSA of 0.5 or less. Sixty patients had negative margins, and 48 patients had positive margins at RP. Cox multivariable regression analysis was performed to identify factors associated with time to secondary PSA failure and included PSA at salvage, year of treatment, Gleason score, ADT use, margin status, T stage, and PSA doubling time. Occurrence of distant metastases was documented.

Results

Median follow-up after radiation was 63.09 months. A total of 24 patients had a distant metastasis. In all patients, ADT use was associated with a decreased risk of recurrence (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.25-0.79;P = .006). On subgroup analysis, ADT was associated with a decreased risk of failure among patients with negative margins (HR, 0.27; 95% CI, 0.12-0.61;P = .002), but not among men with positive margins (HR, 0.78; 95% CI, 0.29-2.10;P = .63).

Conclusions

Even patients followed with ultrasensitive PSA and salvaged early with a PSA ≤ 0.5 seem to benefit from the addition of ADT to salvage radiation. However, this benefit seemed to be limited to men with negative margins; thus, men with positive margins and PSA ≤ 0.5 may be good candidates for salvage radiation alone.

Keywords: ADT, Prostate cancer, Salvage therapy, Surgical margins, Ultrasensitive PSA.

Introduction

Among patients who undergo radical prostatectomy (RP) as definitive treatment for localized prostate cancer, approximately 20% to 40% may experience a prostate-specific antigen (PSA) recurrence.1, 2, and 3Salvage radiotherapy in this setting has been associated with reductions in prostate-cancer specific and overall mortality in select patients. 4 The Radiation Therapy Oncology Group (RTOG) 96-01 randomized trial of salvage radiotherapy with or without 2 years of bicalutamide (Casodex; AstraZeneca Pharmaceuticals LP, London, UK) has suggested that androgen deprivation therapy (ADT) can improve biochemical recurrence-free survival and metastasis-free survival in this patient population. 5 However, the RTOG 96-01 trial was not conducted in the era of ultrasensitive PSA and may have included patients with higher pre-salvage PSA (85% had PSA < 1.6, and 15% had PSA 1.6-4.0) than typically seen today in the salvage setting. Therefore, it remains unknown whether patients followed closely with ultrasensitive PSA and salvaged early at a PSA ≤ 0.5 have the same benefit from ADT. In this study, we examine patients salvaged at a low PSA (≤ 0.5) after RP to determine whether they benefit from the addition of ADT or whether these men may be spared the additional side effects of ADT.6 and 7

Materials and Methods

Patient Selection

A total of 108 patients treated between 1993 and 2010 comprised the patient cohort. All patients received RP, were followed by ultrasensitive PSA, and then underwent salvage radiation at a PSA ≤ 0.5 at Dana Farber Cancer Institute/Brigham and Women's Hospital. Some patients also received ADT as a part of salvage radiation at the discretion of the treating physician. This study was approved by the Dana-Farber/Harvard Cancer Center Institutional Review Board.

Endpoints

The primary endpoint of our study was time to secondary biochemical failure. Secondary failure was defined as a serum PSA value of ≥ 0.1 ng/mL above the post-radiotherapy PSA nadir confirmed by a second PSA measurement that was higher than the first by any amount, by a continued increase in PSA level after treatment, or by the initiation of ADT after treatment.8 and 9Occurrence and time to distant metastasis were documented.

Statistical Analysis

The chi-square test was used to evaluate for differences in baseline characteristics between patients who received and did not receive ADT. Both univariable and Cox multivariable regression analyses were performed to identify factors associated with time to secondary PSA failure. Time zero was the time of initiation of salvage radiation. A separate analysis was completed using distant metastasis as an endpoint. For the Cox multivariable analysis, the covariables included PSA at salvage (continuous), year of salvage (continuous) pathologic Gleason score (8-10 vs. 7 vs. 6 as baseline), ADT use at salvage (yes/no), margin status (positive/negative), pathologic T category (T3 vs. T2), and PSA doubling time. Propensity score analysis was included in the Cox multivariable regression model to control for any nonrandom allocation to treatment groups. Propensity analysis involved calculation of a conditional probability for the receipt of ADT and included the following elements: PSA at salvage, Gleason score of 7, Gleason score of 8 to 10, positive margins, pT3 disease, year of treatment, and PSA doubling time. All analyses were performed using Stata 8.0 (StataCorp LP, College Station, TX). All tests were 2-sided, with a significance level of < 0.05.

Results

Baseline Patient Characteristics

The median age of the patients at salvage radiation was 61 years (range, 47-75 years). The median interval from RP to salvage radiation was 24.8 months. The median PSA at salvage was 0.24 ng/mL (range, 0.01-0.5 ng/mL), and the median follow-up after salvage radiation was 63.09 months. As shown in Table 1 , 43 patients (40%) in the cohort received ADT and 48 patients (44.4%) had positive margins. A total of 24 patients developed distant metastasis, and 63 of 108 patients had high-risk prostate cancer.

Table 1 Patient Baseline Characteristics

Characteristic Entire Cohort

n = 108

No. (% or Range)
ADT

n = 43
No ADT

n = 65
Positive Margin

n = 48
Negative Margin

n = 60
Baseline PSA (before RP)          
 0-10 81 (75%) 35 (81.4%) 46 (70.8%) 33 (68.7%) 48 (80%)
 10-20 21 (19.4%) 5 (11.6%) 16 (24.6%) 12 (25%) 9 (15%)
 >20 2 (1.9%) 1 (2.3%) 1 (1.5%) 2 (4.2%) 0 (0)
 Unknown 4 (3.7%) 2 (4.7%) 2 (3.1%) 1 (2.1%) 3 (5%)
Maximum Gleason score (biopsy)          
 <6 5 (4.6%) 3 (7%) 2 (3.1%) 3 (6.3%) 3 (5%)
 6 24 (22.2%) 11 (25.6%) 13 (20%) 15 (31.2%) 9 (15%)
 7 55 (51%) 20 (46.5%) 35 (53.8%) 21 (43.7%) 34 (56.6%)
 8-10 21 (19.4) 9 (20.9%) 12 (18.5%) 8 (16.7%) 13 (21.7%)
 Unknown 3 (2.8%) 0 (0) 3 (4.6%) 1 (2.1%) 1 (1.7%)
Clinical T-category          
 Tx 10 (9.3%) 4 (9.3%) 6 (9.2%) 7 (14.6%) 3 (5%)
 T1b 1 (0.9%) 1 (2.3%) 0 (0) 1 (2.1%) 0 (0)
 T1c 68 (63%) 31 (72.1%) 37 (57%) 26 (54.2%) 42 (70%)
 T2a 28 (25.9%) 6 (14%) 22 (33.8%) 14 (29.1%) 14 (23.3%)
 T3a 1 (0.9%) 1 (2.3%) 0 (0) 0 (0) 1 (1.7%)
Age at salvage RT 61 (47-75) 61 (47-73) 61 (49-75) 62 (47-73) 61 (48-75)
Median time from RP to salvage RT 24.80 mo 29.01 mo 24.31 mo 19.72 mo 29.95 mo
Median PSA (at salvage) 0.24 (0.01-0.5) ng/mL 0.24 (0.04-0.5) ng/mL 0.24 (0.01-0.50) ng/mL 0.28 (0.03-0.05) ng/mL 0.20 (0.01-0.5) ng/mL
PSA at salvage          
 0.01-0.04 3 (2.8%) 1 (2.3%) 2 (3.1%) 1 (2.1%) 2 (3.3%)
 0.05-0.09 2 (1.9%) 0 (0) 2 (3.1%) 1 (2.1%) 1 (1.6%)
 0.10-0.19 23 (21.3%) 14 (32.6%) 9 (13.8%) 10 (20.8%) 13 (21.7%)
 0.20-0.29 36 (33.3%) 12 (27.9%) 24 (37%) 12 (25%) 24 (40%)
 0.30-0.39 23 (21.3%) 9 (20.9%) 14 (21.5%) 16 (33.3%) 7 (11.7%)
 0.40-0.50 21 (19.4%) 7 (16.3%) 14 (21.5%) 8 (16.7%) 13 (21.7%)
Maximum Gleason score (pathologic):          
 <6 2 (1.8%) 0 (0) 2 (3.1%) 0 (0) 2 (3.3%)
 6 5 (4.6%) 2 (4.6%) 3 (4.6%) 4 (8.3%) 1 (1.7%)
 7 72 (66.7%) 29 (67.4%) 43 (66.2%) 31 (64.6%) 41 (68.3%)
 8-10 29 (26.9%) 12 (28%) 17 (26.1%) 13 (27.1%) 16 (26.7%)
ADT          
 Yes 43 (39.8%) 43 (100%) 0 25 (52.1%) 42 (70%)
 No 65 (60.2%) 0 65 (100%) 23 (47.9%) 18 (30%)
Margins          
 Positive 48 (44.4%) 18 (41.9%) 23 (35.4%) 48 (100%) 0
 Negative 60 (55.6%) 25 (58.1%) 42 (64.6%) 0 60 (100%)
Pathologic T-category          
 pT2 54 (50%) 20 (46.5%) 34 (52.3%) 18 (37.5%) 36 (60%)
 pT3a 29 (26.9%) 14 (32.5%) 15 (23.1%) 16 (33.3%) 12 (20%)
 pT3b 25 (23.1%) 9 (21%) 16 (24.6%) 14 (29.2%) 12 (20%)

Abbreviations: ADT = androgen deprivation therapy; PSA = prostate-specific antigen; RP = radical prostatectomy; RT = radiotherapy.

Salvage radiation was delivered to a mean dose of 66.49 Gy (range, 61.20-72 Gy). Likewise, ADT duration was collected when available and ADT was given for a mean of 6.12 months (range, 3-11 months). Among patients receiving ADT (n = 43), 35% received a gonadotropin-releasing hormone agonist alone and 65% received a gonadotropin-releasing hormone agonist plus bicalutamide. As shown in Table 1 , there were no significant differences in baseline characteristics between patients treated with ADT plus salvage radiation and patients treated with salvage radiation alone, including pathologic stage (P = .24), margins (P = .55), pathologic Gleason score (P = .72), initial PSA (P = .26), PSA at salvage (P = .25), and age at salvage (median age 61 years for both groups).

Outcome Analysis

On univariable analysis of the entire cohort, only ADT use was associated with decreased failure (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.33-0.86;P = .01). Other factors, such as pathologic T stage and Gleason score, were not significantly associated with outcome ( Table 2 ). On multivariable analysis of the entire cohort, PSA at salvage radiation (HR, 20.99; 95% CI, 2.00-219.86;P = .01) and ADT use (HR, 0.44; 95% CI, 0.25-0.79;P = .006) were significantly associated with outcome. No other tumor characteristics were associated with failure. On sensitivity analysis, ADT duration was not associated with failure. For the entire cohort, the 4-year failure-free survival for patients who received ADT was 44.6% compared with 22.8% for patients who did not receive ADT Figure 1 .

Table 2 Cox Regression Analysis for Entire Cohort

Covariables Univariable Analysis Multivariable Analysis
HR 95% CI P Value HR 95% CI P Value
PSA at salvage 4.37 0.69-27.6 .12 20.99 2.00-219.86 .01
Year of salvage 1.00 0.94-1.06 .89 1.19 0.89-1.61 .25
Positive margins 0.69 0.44-1.08 .10 0.91 0.26-3.18 .88
ADT 0.54 0.33-0.86 .01 0.44 0.25-0.79 .006
Gleason 7 1.20 0.47-3.00 .70 2.46 0.52-11.61 .26
Gleason 8-10 1.03 0.39-2.70 .96 1.97 0.45-8.71 .37
pT3 disease 0.94 0.61-1.45 .77 1.18 0.66-2.09 .58
DT 0.99 0.94-1.05 .80 0.93 0.85-1.02 .14
Propensity Score 1.00 0.99-1.01 .38 0.98 0.93-1.04 .52

Abbreviations: ADT = androgen deprivation therapy; CI = confidence interval; HR = hazard ratio; PSA = prostate-specific antigen.

gr1

Figure 1 ADT Versus No ADT Abbreviation: ADT = androgen deprivation therapy.

When the cohort was subdivided into patients with negative (n = 60) versus positive margins (n = 48), ADT was associated with a large and significant reduction in the risk of second failure among patients with negative margins (HR, 0.27; 95% CI, 0.12-0.61;P = .002) Table 3 . Among patients with negative margins, the 4-year failure free survival with ADT was 49.4% compared with 18.1% without ADT Figure 2 . However, this effect was not observed among those with positive margins (HR, 0.78; 95% CI, 0.29-2.1;P = .63) Table 4 . Among patients with positive margins, the 4-year failure-free survival with ADT was 35.5% compared with 31.8% without ADT Figure 3 . There were only 24 distant metastases, and there were no significant associations between the covariable and the time to distant metastases.

Table 3 Cox Regression Analysis in Men With Negative Margins

Covariables Univariable Analysis Multivariable Analysis
HR 95% CI P Value HR 95% CI P Value
ADT 0.47 0.25-0.88 .02 0.27 0.12-0.61 .002
PSA at salvage 2.12 0.19-23.0 .54 8.17 0.30-222.30 .21
Year of salvage 1.04 0.95-1.13 .38 1.09 0.75-1.58 .66
Gleason 7 1.35 0.32-5.67 .68 2.72 0.33-22.42 .35
Gleason 8-10 1.78 0.41-7.76 .45 4.10 0.57-29.35 .16
pT3 disease 0.96 0.54-1.70 .88 1.00 0.45-2.25 .99
DT 1.01 0.95-1.08 .73 0.98 0.87-1.10 .74
Propensity score 1.00 0.99-1.02 .61 1.01 0.94-1.10 .74

Abbreviations: ADT = androgen deprivation therapy; CI = confidence interval; DT = doubling time; HR = hazard ratio; PSA = prostate-specific antigen.

gr3

Figure 2 Negative Margins: ADT Versus No ADT Abbreviation: ADT = androgen deprivation therapy.

Table 4 Cox Regression in Men With Positive Margins

Covariables Univariable Analysis Multivariable Analysis
HR 95% CI P Value HR 95% CI P Value
ADT 0.78 0.36-1.71 .54 0.78 0.29-2.10 .63
PSA at salvage 24.0 1.27-452.25 .03 31.66 0.17-6032.46 .20
Year of salvage 0.95 0.87-1.03 .22 0.64 0.23-1.81 .40
Gleason 7 1.27 0.37-4.34 .71 0.29 0.007-12.57 .52
Gleason 8-10 0.47 0.12-1.92 .30 0.13 0.005-3.48 .22
pT3 disease 0.99 0.47-2.12 1.00 0.55 0.15-1.99 .36
DT 0.95 0.86-1.05 .32 1.00 0.73-1.38 .97
Propensity score 1.00 0.98-1.01 .56 1.09 0.91-1.31 .35

Abbreviations: ADT = androgen deprivation therapy; CI = confidence interval; DT = doubling time; HR = hazard ratio; PSA = prostate-specific antigen.

gr2

Figure 3 Positive Margins: ADT Versus No ADT Abbreviation: ADT = androgen deprivation therapy.

Discussion

In this study, we examined the outcomes of salvage radiation plus or minus ADT in patients followed with ultrasensitive PSA and salvaged early at a PSA of ≤ 0.5. We focused on this population because they are most representative of the patients currently seen in practice, in whom early salvage therapy is often favored.

We found that ADT use among men with negative margins was associated with a significant reduction in the risk of second failure ( Table 2 ), and there was a 31% absolute increase in 4-year failure-free survival with the use of hormones in this subgroup. This association was not observed among men with positive margins.

The clinical implication of this study is that among those men who are followed with ultrasensitive PSA and salvaged early (PSA ≤ 0.5), it is possible that those with positive margins receiving salvage radiation may be safely spared from the morbidity of ADT.

The observed association between ADT and failure-free survival is a plausible one in patients with negative margins. ADT is a systemic therapy that has the ability to reach any distant micro-metastases that are not treated with local radiation. It is more likely that those with negative margins who recur do so because of residual micro-metastatic disease outside of the regional pelvic field covered by radiation, and it is thus reasonable that systemic therapy would benefit these patients, supporting the findings of the RTOG 96-01. Likewise, patients with positive margins are more likely to have had a local recurrence, and it is likely that with a PSA ≤ 0.5, radiotherapy to doses > 60 Gy is enough to eliminate microscopic disease in the prostate bed, and the addition of ADT does not seem to be necessary.10 and 11

These results also support the work by Cheung et al, 12 in which both a favorable group and an unfavorable group were identified for response to salvage radiation alone versus radiation plus ADT. Those patients with positive margins and pre-radiotherapy PSA ≤ 0.5 ng/mL comprised the favorable group who fared well with salvage radiotherapy alone and did not appear to require ADT. Patients with pre-salvage PSA > 0.5 or negative margins were thought to need ADT, which is consistent with the findings of the current study.

Our results do not directly address what to do for patients who have persistently detectable PSA after surgery. Extrapolating from these results, one might hypothesize that as long as the persistent PSA is ≤ 0.5, those with negative margins should receive adjuvant radiation plus ADT and those with positive margins may receive adjuvant radiation alone, but this will need to be tested in a cohort exclusively of men with persistently detectable postoperative PSA.

There are certain points that deserve additional consideration. As in most other studies on this topic, we conducted a retrospective study, and the data presented are not from a prospective randomized trial. Second, only 24 patients experienced a distant metastasis, and when this was used as the endpoint for analysis, there were no significant results; thus, our study focuses on the endpoint of biochemical failure. In the RTOG 96.01, a 17% difference in biochemical failure-free survival translated to a 5% difference in distant metastases, and it is reasonable to expect that with further follow-up of our cohort the results observed with biochemical failure could lead to a reduction in metastases. It would be ideal with further follow-up to also know the impact of ADT on freedom from distant metastases, prostate cancer–specific mortality, and overall survival. 2 Another point to consider is that in this study, 41% of the patients had a PSA of 0.3 to 0.5 by the time they received salvage radiation, and with the growing evidence that earlier initiation of salvage radiation at lower PSA levels is better, more patients will likely be receiving salvage radiation at even lower PSA levels (ie, < 0.3). Whether ADT is still useful for patients with negative margins and PSA < 0.3 will need to be specifically tested in a larger series, but given the presumed distant component of recurrence in patients with negative margins, it is likely that ADT will still have a benefit in these patients.

Finally, it should be noted that although we did not observe a significant benefit to the use of ADT in men with positive margins and a PSA ≤ 0.5, those with local-only disease may have a protracted disease course, and so it remains possible that with further follow-up and larger cohorts it would be possible to detect a significant benefit to ADT in men with positive margins. In our study, the nonsignificant HR for the impact of ADT with positive margins was 0.78, which is less profound than the significant HR of 0.27 due to ADT for men with negative margins. However, even if the 0.78 HR for men with positive margins was significant, clinicians would still need to decide whether this relatively small risk reduction would be worth the additional side effects of ADT, and for many patients with slowly growing disease, this trade-off may not be worthwhile. Clearly, though, further follow-up is needed to completely rule out a benefit in this positive margin group.

Conclusions

Even patients followed with ultrasensitive PSA and salvaged early with a PSA ≤ 0.5 seem to benefit from the addition of ADT to salvage radiation. However, this benefit seemed to be limited to men with negative margins. Men with positive margins and PSA ≤ 0.5 may be good candidates for salvage radiation alone.

Clinical Practice Points

 

  • Standard therapy for patients who develop a PSA recurrence after RP includes salvage radiotherapy, because it has been associated with reductions in prostate cancer–specific and overall mortality in certain patients. Recent results from randomized trial RTOG 96-01 suggest that the addition of ADT to salvage radiation therapy can offer improved PSA failure-free survival and decreased distant metastasis, but it is unknown whether ADT is also needed in contemporary patients who are typically followed with ultrasensitive PSA and salvaged at lower values (ie, ≤ 0.5).
  • In our patient cohort, all of whom were followed by ultrasensitive PSA and given salvage RT with a PSA ≤ 0.5, ADT was associated with a significantly decreased risk of recurrence. Moreover, on subgroup analysis, we find that this benefit is observed among patients with negative margins but not those with positive margins.
  • The implications of our findings for clinical practice are that even those patients followed with ultrasensitive PSA after RP and salvaged with PSA ≤ 0.5 may benefit from ADT in addition to salvage radiation. Our results suggest that this benefit may be limited to men with negative margins, and thus patients with positive margins likely could be spared the additional side effects of ADT and be treated with radiation alone.

Disclosure

PLN has consulted for Medivation Inc and Ferring Inc. All other authors have stated that they have no conflicts of interest.

Acknowledgments

This work was supported by the Doris Duke Charitable Foundation Clinical Research Fellowship at Harvard Medical School, Fitz’s Cancer Warriors, Hugh Simons in Honor of Frank and Anne Simons, David and Cynthia Chapin, The Prostate Cancer Foundation, and a grant from an anonymous family foundation.

References

  • 1 D.A. Ahove, K.E. Hoffman, J.C. Hu, T.K. Choueiri, A.V. D'Amico, P.L. Nguyen. Which patients with undetectable PSA levels 5 years after radical prostatectomy are still at risk of recurrence?–implications for a risk-adapted follow-up strategy. Urology. 2010;76:1201-1205 Crossref
  • 2 C.R. Pound, A.W. Partin, M.A. Eisenberger, D.W. Chan, J.D. Pearson, P.C. Walsh. Natural history of progression after PSA elevation following radical prostatectomy. JAMA. 1999;281:1591-1597 Crossref
  • 3 J. Walz, F.K. Chun, E.A. Klein, et al. Nomogram predicting the probability of early recurrence after radical prostatectomy for prostate cancer. J Urol. 2009;181:601-608 Crossref
  • 4 B.J. Trock, M. Han, S.J. Freedland, et al. Prostate cancer-specific survival following salvage radiotherapy vs observation in men with biochemical recurrence after radical prostatectomy. JAMA. 2008;99:2760-2769 Crossref
  • 5 Shipley WU. Initial report of RTOG 9601, a phase III trial in prostate cancer: effect of anti-androgen therapy (AAT) with bicalutamide during and after radiation therapy (RT) on freedom from progression and incidence of metastatic disease in patients following radical prostatectomy (RP) with pT2-3,N0 disease and elevated PSA levels. 2011 Feb 17 Genitoruinary Cancers Symposium, American Society of Clinical Oncology; Orlando, FL.
  • 6 P.J. Saylor, M.R. Smith. Adverse effects of androgen deprivation therapy: defining the problem and promoting health among men with prostate cancer. J Natl Compr Canc Netw. 2010;8:211-223
  • 7 M.R. Smith, H. Lee, D.M. Nathan. Insulin sensitivity during combined androgen blockade for prostate cancer. J Clin Endocrinol Metab. 2006;91:1305-1308 Crossref
  • 8 A.J. Stephenson, S.F. Shariat, M.J. Zelefsky, et al. Salvage radiotherapy for recurrent prostate cancer after radical prostatectomy. JAMA. 2004;291:1325-1332 Crossref
  • 9 A.J. Stephenson, P.T. Scardino, M.W. Kattan, et al. Predicting the outcome of salvage radiation therapy for recurrent prostate cancer after radical prostatectomy. J Clin Oncol. 2007;25:2035-2041 Crossref
  • 10 J.L. Wright, B.L. Dalkin, L.D. True, et al. Positive surgical margins at radical prostatectomy predict prostate cancer specific mortality. J Urol. 2010;183:2213-2218 Crossref
  • 11 T.H. Van der Kwast, M. Bolla, H. Van Poppel, et al. Identification of patients with prostate cancer who benefit from immediate postoperative radiotherapy: EORTC 22911. J Clin Oncol. 2007;25:4178-4186 Crossref
  • 12 R. Cheung, A.M. Kamat, R. de Crevoisier, et al. Outcome of salvage radiotherapy for biochemical failure after radical prostatectomy with or without hormonal therapy. Int J Radiat Oncol Biol Phys. 2005;63:134-140 Crossref

Footnotes

1 Department of Radiation Oncology, Dana Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA

2 Department of Statistics, University of Connecticut, Storrs, CT

3 Department of Radiation Oncology, Boston Medical Center, Boston University School of Medicine, Boston, MA

4 Department of Medical Oncology, Dana Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA

Address for correspondence: Paul L. Nguyen, MD, Dana Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115 Fax: 617-975-0912