Use of Postprostatectomy Radiation Therapy at an NCI-Designated Comprehensive Cancer Center

Purpose: Characterize use of postprostatectomy radiation (PPRT) for patients with prostate cancer at an NCI-designated comprehensive cancer center. Methods: We queried our prospective prostate cancer database for patients treated with 60 to 68 Gy of radiation therapy (RT) to the prostate bed after prostatectomy from 2003 to 2011. Prostatectomy cases were obtained from billing records. Patients with an intact prostate treated with definitive RT served as a control for the change in volume of patients with prostate cancer treated in the department. Chi-square analysis assessed differences between adjuvant and salvage RT cohorts. Spearman correlation assessed yearly trends in prostate-specific antigen (PSA) level at the time of referral for RT. Linear regression models tested trends for number of PPRT cases, prostatectomies, and patients with intact prostate receiving radiation across years. Results: PPRT was used to treat 475 men at Fox Chase Cancer Center from 2003 to 2011 (83 adjuvant and 392 salvage). Over time, an increased proportion of patients receiving RT to the prostate were treated with PPRT. No increase was seen in the proportion of patients treated with adjuvant RT compared with salvage RT (P=.5). Patients receiving adjuvant RT were younger, had higher pathologic Gleason score, pathologic T stage, and rates of positive margins than those receiving salvage RT. Pre-RT PSA values were inversely correlated with year (P=.005). The number of patients referred for salvage RT with a PSA of 0.5 ng/mL or less increased significantly from 7.9% in 2003 to 26.6% in 2011 (P=.002). Conclusions: A larger proportion of patients treated with RT for localized prostate cancer are now receiving PPRT. No increase was seen in the proportion of patients treated with adjuvant RT. Over time, patients with lower PSAs were referred for salvage RT.

Abstract

Purpose: Characterize use of postprostatectomy radiation (PPRT) for patients with prostate cancer at an NCI-designated comprehensive cancer center. Methods: We queried our prospective prostate cancer database for patients treated with 60 to 68 Gy of radiation therapy (RT) to the prostate bed after prostatectomy from 2003 to 2011. Prostatectomy cases were obtained from billing records. Patients with an intact prostate treated with definitive RT served as a control for the change in volume of patients with prostate cancer treated in the department. Chi-square analysis assessed differences between adjuvant and salvage RT cohorts. Spearman correlation assessed yearly trends in prostate-specific antigen (PSA) level at the time of referral for RT. Linear regression models tested trends for number of PPRT cases, prostatectomies, and patients with intact prostate receiving radiation across years. Results: PPRT was used to treat 475 men at Fox Chase Cancer Center from 2003 to 2011 (83 adjuvant and 392 salvage). Over time, an increased proportion of patients receiving RT to the prostate were treated with PPRT. No increase was seen in the proportion of patients treated with adjuvant RT compared with salvage RT (P=.5). Patients receiving adjuvant RT were younger, had higher pathologic Gleason score, pathologic T stage, and rates of positive margins than those receiving salvage RT. Pre-RT PSA values were inversely correlated with year (P=.005). The number of patients referred for salvage RT with a PSA of 0.5 ng/mL or less increased significantly from 7.9% in 2003 to 26.6% in 2011 (P=.002). Conclusions: A larger proportion of patients treated with RT for localized prostate cancer are now receiving PPRT. No increase was seen in the proportion of patients treated with adjuvant RT. Over time, patients with lower PSAs were referred for salvage RT.

Radical prostatectomy is the most commonly used treatment for localized prostate cancer in the United States,1 and its popularity has been growing since the introduction of robotic-assisted prostatectomy.2 Approximately one-third of men undergoing prostatectomy will have high-risk pathologic features, such as extracapsular extension, seminal vesicle invasion, or positive surgical margins.3,4 Three randomized trials have shown a benefit for treating these men with adjuvant radiation to the prostate bed, with one trial showing an overall survival advantage.57 Despite these data, considerable disagreement remains about the appropriate timing of postprostatectomy radiation therapy (PPRT).8 Because not all men with high-risk pathologic features will experience disease recurrence, some practitioners believe that the risk of recurrence with high-risk features is not sufficiently high to offset the potential toxicity of adjuvant treatment. An alternative strategy has been to treat at the time of biochemical recurrence, and at that point use salvage radiation therapy (RT) to the prostate bed.9

We examined our institutional database to assess how the use of PPRT has changed recently at our NCI-designated comprehensive cancer center in light of phase III data showing the efficacy of adjuvant RT. Our hypothesis is that there has been a trend toward increased use of PPRT since 2006, following the publication of initial results from EORTC 22911 and SWOG 8794 showing a benefit for adjuvant PPRT compared with observation.6,7

Methods

We queried our prospective prostate cancer database for patients who received RT to the prostate bed after prostatectomy from 2003 to 2011. Patients receiving a prescription dose ranging from 60 to 68 Gy were selected for study inclusion, and those with metastatic disease were excluded.

RT was defined as adjuvant if patients started RT within 1 year of surgery,10 and if they were referred based on a high-risk factor identified on pathologic assessment of the surgical specimen (T3 disease [extracapsular extension or seminal vesicle invasion], a positive margin, or Gleason score 8–10). A detectable prostate-specific antigen (PSA) level was allowed in the adjuvant definition as long as only one postoperative PSA result was obtained in the setting of the preceding high-risk factors and was less than 0.2 ng/mL; patients with a detectable PSA level less than 0.2 ng/mL are not accounted for in the American Urological Association (AUA) guidelines.11 RT was defined as salvage if given in the setting of an increasing PSA level, a single postoperative PSA level of 0.2 ng/mL or greater, or a documented clinical recurrence via imaging or digital rectal examination. To assess for a potential change in referral patterns of patients receiving salvage RT, a PSA threshold of 0.5 ng/mL or less was used to determine which patients were being referred for early salvage.9

The number of patients with an intact prostate treated with definitive RT was recorded by year as a control for changing volume among patients with total prostate in the department. Additionally, the billing records of Fox Chase Cancer Center (FCCC) were queried for the number of prostatectomies performed at the institution in a given year. Because the prostatectomy billing records were available only between 2003 and 2011, we limited our RT cohort to the same period. Clinical and pathologic data were not available for patients undergoing prostatectomy alone and did not receive PPRT.

Chi-square analysis was used to assess differences between patient cohorts receiving adjuvant and salvage RT. Spearman correlation was used to assess yearly trends in PSA level at time of referral for RT. Linear regression models were used to test the trend of number of PPRT cases, number of prostatectomies, and number of patients with an intact prostate receiving radiation across years respectively. Because of the limited number of years for which complete data were available, only univariate analyses were performed.

Results

From 2003 to 2011, 475 patients received PPRT at FCCC (83 adjuvant and 392 salvage). The patient characteristics and descriptives are listed in Table 1. Patients were more likely to receive adjuvant RT if they were younger (P=.0013), had a positive surgical margin (P<.0001), had a higher pathologic Gleason score (P=.0071), and had a higher pathologic T stage (P<.0001). The postprostatectomy PSA level was also significantly lower (P<.0001), as was expected given the definition of adjuvant RT applied.

During the period of this study, an increasing proportion of patients treated with RT for localized prostate cancer at FCCC were treated in the postprostatectomy setting. The proportion of patients with localized prostate cancer treated with PPRT steadily increased from 9.4% in 2003 to a high of 26.6% in 2011 (Figure 1). During that time, a significant increase was seen in the number of prostatectomies performed at FCCC (P=.02), with a corresponding increase in PPRT use. The increase in the number of patients treated with RT to an intact prostate remained relatively stable over the same period (Figure 2). Regression model analysis found a significant correlation between year of treatment and number of PPRT cases (P=.002), and between number of surgical cases and number of PPRT cases (P=.02). No significant correlation was seen between the number of patients with an intact prostate treated with radiation and the number of patients treated with PPRT (P=.709).

The proportion of patients receiving adjuvant RT did not increase compared with those receiving salvage RT (P=.5; Figure 3). Pre-RT PSA values were inversely correlated with year of treatment (P=.005). A trend was seen toward an increasing proportion of patients referred with a pathologic Gleason score of 8 or more (P=.1; Figure 4). When considering only patients receiving salvage RT with a PSA level of 0.5 ng/mL or less, a significant increase was seen in the number of patients referred for early salvage RT versus those referred with higher PSA levels (P=.0018; Figure 4). Examination of the proportion of patients with high-risk pathologic features (positive margin and/or ≥pT3 disease) revealed no difference in annual proportion receiving adjuvant or salvage treatment over time (P=.58).

Table 1

Patient Characteristics Stratified by Adjuvant and Salvage Status

Table 1

Discussion

This review of the institutional practice pattern of PPRT has demonstrated an increased use of RT in the postprostatectomy setting for men with localized prostate cancer. PPRT now accounts for approximately 25% of the patients with localized prostate cancer being treated with definitive RT at FCCC. This increase has occurred despite the number of patients remaining stable who have an intact prostate cancer treated with definitive external-beam RT at FCCC. Potential explanations for the change in patient distribution include the increased number of prostatectomies performed at our institution and in the region,12 or the possible increased awareness among urologists of the benefit of referring patients for PPRT given the findings of recent randomized studies.5,6,13

The increase in prostatectomies at FCCC is likely related to the introduction of the robotic prostatectomy in 2006, with more than 97% of the prostatectomies performed robotically since, and the addition of 2 urologic oncologists between 2007 and 2011. An increased number of prostatectomies is also consistent with what has been shown nationally,14 which has been attributed to the popular use of robot-assisted prostatectomies.2 The increase in patients who have undergone PPRT logically corresponds with the escalation in surgical volume. Although we did not have clinical surgical data available for this analysis, we did observe a trend toward

Figure 1
Figure 1

Patients with localized prostate cancer treated with RT at Fox Chase Cancer Center.

Abbreviations: PPRT, postprostectomy radiation therapy; RT, radiation therapy.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 13, 5; 10.6004/jnccn.2015.0072

a greater number of patients being referred for PPRT with a Gleason score 8 or more. Because referrals for adjuvant PPRT did not increase, this trend likely reflects an increased number of high-risk patients undergoing prostatectomies.

Adjuvant PPRT has been shown to reduce the risk of biochemical recurrence, local recurrence, and clinical progression of prostate cancer compared with radical prostatectomy alone for men with high-risk

Figure 2
Figure 2

Number of patients with localized prostate cancer treated with prostatectomy, definitive radiation therapy, and PPRT by year. Abbreviations: PPRT, postprostectomy radiation therapy.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 13, 5; 10.6004/jnccn.2015.0072

pathologic features after prostatectomy (positive resection margin, extracapsular extension, or seminal vesicle invasion) in 3 randomized trials.15 The first of these trials (EORTC 2291113) was published in 2005 and demonstrated an improvement in biochemical progression-free survival that has remained significant with 10-year follow-up.7 Similarly, ARO 96-02 also demonstrated a biochemical progression-free survival.5 Although SWOG 8794 was not controlled for PSA level at the time of study entry, long-term results published in 2009 were the first to exhibit an improvement in the rate of distant metastases and an overall survival benefit associated with adjuvant PPRT.16 At FCCC, no significant increase was seen in adjuvant PPRT over the course of the study period. This could be attributed to the controversy that exists regarding the appropriate timing of PPRT and the reservations regarding the interpretation of these 3 randomized trials.8,17

Because of concerns that adjuvant radiation requires delivering radiation to patients who may not require additional treatment after prostatectomy, salvage RT is a strategy that uses radiation only after the patient’s PSA level increases. A retrospective analysis by Trock et al18 demonstrated that RT within 2 years of biochemical recurrence improved prostate cancer–specific survival if the PSA doubling time was less than 6 months. An analysis of more than 1500 patients by Stephenson et al19 found that approximately 50% of patients who received salvage RT alone with a PSA level of 0.5 ng/mL or less were free from progression at 6 years compared with only 26% for those with higher PSAs. Given the current lack of randomized evidence comparing adjuvant and salvage PPRT, Briganti et al9 performed a multi-institutional match-controlled analysis comparing adjuvant RT with observation followed by early salvage RT (postoperative PSA level ≤0.5 ng/mL at least 6 months after surgery) as needed. Early salvage RT had an equivalent 5-year biochemical control compared with adjuvant RT for patients with pT3pN0 disease, and resulted in only 45% of patients in the observation/early salvage RT group requiring treatment, thus minimizing potential overtreatment. The role of ultrasensitive PSA in the postprostatectomy setting, which has been shown to be capable of predicting which patients are more or less likely to experience recurrence,20,21 remains in question given the variability at such low levels. This question of adjuvant RT versus early salvage RT will hopefully be answered by the 2 ongoing randomized clinical trials: the Medical Research Council/National Cancer Institute of Canada Intergroup RADICALS (Radiotherapy and Androgen Deprivation in Combination after Local Surgery) trial22 and the Trans Tasman Radiation Oncology Group RAVES (Radiotherapy - Adjuvant Versus Early Salvage) trial (ClinicalTrials. gov identifier: NCT00860652).

Taking into account the data currently available, current NCCN Guidelines for Prostate Cancer recommend that, “evidence supports offering adjuvant/salvage RT in most men with adverse pathologic features or detectable PSA and no evidence of disseminated disease”10 (to view the most recent version of these guidelines, visit NCCN.org). Given our data showing a stable percentage of patients undergoing adjuvant RT and a significant increase in the number of patients being treated with a PSA level of 0.5 ng/mL or less, the institutional bias seems to be favoring a strategy of observation/early salvage RT over adjuvant RT for most men with high-risk pathologic features.

In a recent survey of urologists and radiation oncologists, practitioners from both specialties reported that large randomized clinical trials were the level of evidence most likely to change treatment recommendations for localized prostate cancer.23 A SEER analysis by Hoffman et al24 in 2011 found that younger age, Gleason score of 8 or greater, positive margin, and pT3a and pT3b were associated with a higher likelihood of receiving PPRT, consistent with the results of our study. From 2000 to 2007, they did not observe an increase in the use of PPRT in relation to the presentation of the EORTC 22911 and SWOG 8794 results in 2004 and 2005, respectively. Similarly, in a SEER-Medicare analysis of patients treated from 2000 to 2006, Sheets et al25 found little increase in the rate of PPRT since the publication of the randomized trials. In our institutional analysis, we were able to follow patients to a more recent time point (2011), which includes the 2009 publication of a third randomized trial (ARO 96-02) and the overall survival benefit seen in the SWOG trial.5,16 Although we did not show a significant increase in the rate of adjuvant RT, we did find that PPRT now comprises a larger proportion of patients with localized prostate cancer treated with radiation.

Limitations of this study include those related to the fact that it was a single-institution analysis.

Figure 3
Figure 3

Trend of patients treated with postprostectomy radiation therapy (PPRT) receiving adjuvant or salvage radiation (P=.5).

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 13, 5; 10.6004/jnccn.2015.0072

FCCC is located in a region of dense health care supply, with many options for patients to choose from regarding where to receive care, including 2 NCI-designated comprehensive cancer centers within 15 miles of each other. We know that not all patients receiving PPRT also had surgery at FCCC. It is also likely that not all surgical patients remained at our institution if they required PPRT. This precludes us from being able to precisely analyze the trend of whether men are more or less likely to receive PPRT after prostatectomy. Another limitation of this study
Figure 4
Figure 4

Trend of patients undergoing salvage PPRT stratified by pre-RT PSA <0.5 ng/mL or ≥0.5 ng/mL (P=.0018).

Abbreviations: PPRT, postprostectomy radiation therapy; PSA, prostate-specific antigen; RT, radiation therapy.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 13, 5; 10.6004/jnccn.2015.0072

is the lack of clinical data for the patients undergoing prostatectomy (specifically pathologic data) that would help to better define changes in the pattern of referrals for PPRT. That information would also help determine the percentage of patients undergoing prostatectomy that met the criteria from the randomized trials for adjuvant RT versus the number of patients actually referred for adjuvant RT.

Conclusions

For radiation oncologists treating prostate cancer at FCCC, a significant trend in the composition of patients being treated with radiation is seen, from greater than 90% of patients being treated with an intact prostate in the early 2000s to more recently approximately 25% of patients being treated after a prostatectomy. This change seems to be largely driven by increased surgical volume, rather than by a data-driven increase in referrals for adjuvant RT based on the results of the phase III trials supporting adjuvant radiation.5,7,16 At FCCC, referral of patients for salvage RT has trended toward an increase in early salvage in patients with PSA levels less than 0.5 ng/mL, rather than immediate referral for adjuvant RT. Further studies should validate these findings in a larger data set, such as a national oncology database, and conduct comparative effectiveness research to evaluate the utilization trends among available treatment modalities for localized prostate cancer.

The authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.

This publication was supported by grant number P30 CA006927 from the National Cancer Institute, NIH. In addition, this publication was supported in part by a grant from Varian Medical Systems, Inc.

References

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    SwindlePEasthamJAOhoriM. Do margins matter? The prognostic significance of positive surgical margins in radical prostatectomy specimens. J Urol2005;174:903907.

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    BluteMLBergstralhEJIoccaA. Use of Gleason score, prostate specific antigen, seminal vesicle and margin status to predict biochemical failure after radical prostatectomy. J Urol2001;165:119125.

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    • Export Citation
  • 5.

    WiegelTBottkeDSteinerU. Phase III postoperative adjuvant radiotherapy after radical prostatectomy compared with radical prostatectomy alone in pT3 prostate cancer with postoperative undetectable prostate-specific antigen: ARO 96-02/AUO AP 09/95. J Clin Oncol2009;27:29242930.

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    ThompsonIMJrTangenCMParadeloJ. Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial. JAMA2006;296:23292335.

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    BollaMvan PoppelHTombalB. Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: long-term results of a randomised controlled trial (EORTC trial 22911). Lancet2012;380:20182027.

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    KingCR. Adjuvant versus salvage radiotherapy for high-risk prostate cancer patients. Semin Radiat Oncol2013;23:215221.

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    BrigantiAWiegelTJoniauS. Early salvage radiation therapy does not compromise cancer control in patients with pT3N0 prostate cancer after radical prostatectomy: results of a match-controlled multi-institutional analysis. Eur Urol2012;62:472487.

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    StitzenbergKBWongYNNielsenME. Trends in radical prostatectomy: centralization, robotics, and access to urologic cancer care. Cancer2012;118:5462.

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    BollaMvan PoppelHColletteL. Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911). Lancet2005;366:572578.

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    MartinJMHandorfEAKutikovA. The rise and fall of prostate brachytherapy: use of brachytherapy for the treatment of localized prostate cancer in the National Cancer Data Base. Cancer2014;120:21142121.

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    • Export Citation
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    ValicentiRKThompsonIJrAlbertsenP. Adjuvant and salvage radiation therapy after prostatectomy: American Society for Radiation Oncology/American Urological Association guidelines. Int J Radiat Oncol Biol Phys2013;86:822828.

    • Search Google Scholar
    • Export Citation
  • 16.

    ThompsonIMTangenCMParadeloJ. Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: long-term followup of a randomized clinical trial. J Urol2009;181:956962.

    • Search Google Scholar
    • Export Citation
  • 17.

    TrockBJ. Adjuvant radiation following radical prostatectomy: what are the known unknowns?Eur Urol2014;66:251252.

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    TrockBJHanMFreedlandSJ. Prostate cancer-specific survival following salvage radiotherapy vs observation in men with biochemical recurrence after radical prostatectomy. JAMA2008;299:27602769.

    • Search Google Scholar
    • Export Citation
  • 19.

    StephensonAJScardinoPTKattanMW. Predicting the outcome of salvage radiation therapy for recurrent prostate cancer after radical prostatectomy. J Clin Oncol2007;25:20352041.

    • Search Google Scholar
    • Export Citation
  • 20.

    ShenSLeporHYaffeeRTanejaSS. Ultrasensitive serum prostate specific antigen nadir accurately predicts the risk of early relapse after radical prostatectomy. J Urol2005;173:777780.

    • Search Google Scholar
    • Export Citation
  • 21.

    Taylor JAIIIKoffSGDauserDAMcLeodDG. The relationship of ultrasensitive measurements of prostate-specific antigen levels to prostate cancer recurrence after radical prostatectomy. BJU Int2006;98:540543.

    • Search Google Scholar
    • Export Citation
  • 22.

    ParkerCClarkeNLogueJ. RADICALS (Radiotherapy and Androgen Deprivation in Combination after Local Surgery). Clin Oncol (R Coll Radiol)2007;19:167171.

    • Search Google Scholar
    • Export Citation
  • 23.

    HanLCDelpeSShahND. Perceptions of radiation oncologists and urologists on sources and type of evidence to inform prostate cancer treatment decisions. Int J Radiat Oncol Biol Phys2014;89:277283.

    • Search Google Scholar
    • Export Citation
  • 24.

    HoffmanKENguyenPLChenMH. Recommendations for post-prostatectomy radiation therapy in the United States before and after the presentation of randomized trials. J Urol2011;185:116120.

    • Search Google Scholar
    • Export Citation
  • 25.

    SheetsNCHendrixLHAllenIMChenRC. Trends in the use of postprostatectomy therapies for patients with prostate cancer: a Surveillance, Epidemiology, and End Results Medicare analysis. Cancer2013;119:3295330.

    • Search Google Scholar
    • Export Citation

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Correspondence: Eric M. Horwitz, MD, Department of Radiation Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111. E-mail: Eric.Horwitz@fccc.edu

Article Sections

Figures

  • View in gallery

    Patients with localized prostate cancer treated with RT at Fox Chase Cancer Center.

    Abbreviations: PPRT, postprostectomy radiation therapy; RT, radiation therapy.

  • View in gallery

    Number of patients with localized prostate cancer treated with prostatectomy, definitive radiation therapy, and PPRT by year. Abbreviations: PPRT, postprostectomy radiation therapy.

  • View in gallery

    Trend of patients treated with postprostectomy radiation therapy (PPRT) receiving adjuvant or salvage radiation (P=.5).

  • View in gallery

    Trend of patients undergoing salvage PPRT stratified by pre-RT PSA <0.5 ng/mL or ≥0.5 ng/mL (P=.0018).

    Abbreviations: PPRT, postprostectomy radiation therapy; PSA, prostate-specific antigen; RT, radiation therapy.

References

  • 1.

    CooperbergMRBroeringJMLitwinMS. The contemporary management of prostate cancer in the United States: lessons from the cancer of the prostate strategic urologic research endeavor (CapSURE), a national disease registry. J Urol2004;171:13931401.

    • Search Google Scholar
    • Export Citation
  • 2.

    BarbashGIGliedSA. New technology and health care costs—the case of robot-assisted surgery. N Engl J Med2010;363:701704.

  • 3.

    SwindlePEasthamJAOhoriM. Do margins matter? The prognostic significance of positive surgical margins in radical prostatectomy specimens. J Urol2005;174:903907.

    • Search Google Scholar
    • Export Citation
  • 4.

    BluteMLBergstralhEJIoccaA. Use of Gleason score, prostate specific antigen, seminal vesicle and margin status to predict biochemical failure after radical prostatectomy. J Urol2001;165:119125.

    • Search Google Scholar
    • Export Citation
  • 5.

    WiegelTBottkeDSteinerU. Phase III postoperative adjuvant radiotherapy after radical prostatectomy compared with radical prostatectomy alone in pT3 prostate cancer with postoperative undetectable prostate-specific antigen: ARO 96-02/AUO AP 09/95. J Clin Oncol2009;27:29242930.

    • Search Google Scholar
    • Export Citation
  • 6.

    ThompsonIMJrTangenCMParadeloJ. Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial. JAMA2006;296:23292335.

    • Search Google Scholar
    • Export Citation
  • 7.

    BollaMvan PoppelHTombalB. Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: long-term results of a randomised controlled trial (EORTC trial 22911). Lancet2012;380:20182027.

    • Search Google Scholar
    • Export Citation
  • 8.

    KingCR. Adjuvant versus salvage radiotherapy for high-risk prostate cancer patients. Semin Radiat Oncol2013;23:215221.

  • 9.

    BrigantiAWiegelTJoniauS. Early salvage radiation therapy does not compromise cancer control in patients with pT3N0 prostate cancer after radical prostatectomy: results of a match-controlled multi-institutional analysis. Eur Urol2012;62:472487.

    • Search Google Scholar
    • Export Citation
  • 10.

    MohlerJLArmstrongAJBahnsonRR. NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer. Version 2 2014. Available at: NCCN.org. Accessed May 28 2014.

    • Search Google Scholar
    • Export Citation
  • 11.

    ThompsonIMValicentiRKAlbertsenP. Adjuvant and salvage radiotherapy after prostatectomy: AUA/ASTRO Guideline. J Urol2013;190:441449.

  • 12.

    StitzenbergKBWongYNNielsenME. Trends in radical prostatectomy: centralization, robotics, and access to urologic cancer care. Cancer2012;118:5462.

    • Search Google Scholar
    • Export Citation
  • 13.

    BollaMvan PoppelHColletteL. Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911). Lancet2005;366:572578.

    • Search Google Scholar
    • Export Citation
  • 14.

    MartinJMHandorfEAKutikovA. The rise and fall of prostate brachytherapy: use of brachytherapy for the treatment of localized prostate cancer in the National Cancer Data Base. Cancer2014;120:21142121.

    • Search Google Scholar
    • Export Citation
  • 15.

    ValicentiRKThompsonIJrAlbertsenP. Adjuvant and salvage radiation therapy after prostatectomy: American Society for Radiation Oncology/American Urological Association guidelines. Int J Radiat Oncol Biol Phys2013;86:822828.

    • Search Google Scholar
    • Export Citation
  • 16.

    ThompsonIMTangenCMParadeloJ. Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: long-term followup of a randomized clinical trial. J Urol2009;181:956962.

    • Search Google Scholar
    • Export Citation
  • 17.

    TrockBJ. Adjuvant radiation following radical prostatectomy: what are the known unknowns?Eur Urol2014;66:251252.

  • 18.

    TrockBJHanMFreedlandSJ. Prostate cancer-specific survival following salvage radiotherapy vs observation in men with biochemical recurrence after radical prostatectomy. JAMA2008;299:27602769.

    • Search Google Scholar
    • Export Citation
  • 19.

    StephensonAJScardinoPTKattanMW. Predicting the outcome of salvage radiation therapy for recurrent prostate cancer after radical prostatectomy. J Clin Oncol2007;25:20352041.

    • Search Google Scholar
    • Export Citation
  • 20.

    ShenSLeporHYaffeeRTanejaSS. Ultrasensitive serum prostate specific antigen nadir accurately predicts the risk of early relapse after radical prostatectomy. J Urol2005;173:777780.

    • Search Google Scholar
    • Export Citation
  • 21.

    Taylor JAIIIKoffSGDauserDAMcLeodDG. The relationship of ultrasensitive measurements of prostate-specific antigen levels to prostate cancer recurrence after radical prostatectomy. BJU Int2006;98:540543.

    • Search Google Scholar
    • Export Citation
  • 22.

    ParkerCClarkeNLogueJ. RADICALS (Radiotherapy and Androgen Deprivation in Combination after Local Surgery). Clin Oncol (R Coll Radiol)2007;19:167171.

    • Search Google Scholar
    • Export Citation
  • 23.

    HanLCDelpeSShahND. Perceptions of radiation oncologists and urologists on sources and type of evidence to inform prostate cancer treatment decisions. Int J Radiat Oncol Biol Phys2014;89:277283.

    • Search Google Scholar
    • Export Citation
  • 24.

    HoffmanKENguyenPLChenMH. Recommendations for post-prostatectomy radiation therapy in the United States before and after the presentation of randomized trials. J Urol2011;185:116120.

    • Search Google Scholar
    • Export Citation
  • 25.

    SheetsNCHendrixLHAllenIMChenRC. Trends in the use of postprostatectomy therapies for patients with prostate cancer: a Surveillance, Epidemiology, and End Results Medicare analysis. Cancer2013;119:3295330.

    • Search Google Scholar
    • Export Citation

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