Timing and patterns of recurrences and deaths from prostate cancer following adjuvant pelvic radiotherapy for pathologic stage T3/4 adenocarcinoma of the prostate

Abstract

To determine the timing and patterns of late recurrence after radical prostatectomy (RP) alone or RP plus adjuvant radiotherapy (RT). Between 1970 and 1983, 159 patients underwent RP for newly diagnosed adenocarcinoma of the prostate and were found to have positive surgical margins, extracapsular extension and/or seminal vesicle invasion. Of these, 46 received adjuvant RT and 113 did not. The RT group generally received 45–50 Gy to the whole pelvis, then a boost to the prostate bed (total dose of 55–65 Gy). In the RP group, 62% received neoadjuvant/adjuvant androgen deprivation vs 17% in the RT group. Patients were analyzed with respect to timing and patterns of failure. Only one patient was lost to follow-up. The median follow-up for surviving patients was nearly 20 years. The median time to failure in the surgery group was 7.5 vs 14.7 years in the RT group (P=0.1). Late recurrences were less common in the surgery group than the RT group (9 and 1% at 10 and 15 years, respectively vs 17 and 9%). In contrast to recurrences, nearly half of deaths from prostate cancer occurred more than 10 years after treatment. Deaths from prostate cancer represented 55% of all deaths in these patients. Recurrences beyond 10 years after RP in this group of patients were relatively uncommon. Despite its long natural history, death from prostate cancer was the most common cause of mortality in this population with locally advanced tumors, reflecting the need for more effective therapy.

Introduction

One of the most controversial topics in urologic oncology is the role of adjuvant therapy after radical prostatectomy (RP) for those patients at high risk for recurrence. For patients at high risk of local failure, that is, those with positive surgical margins, adjuvant radiotherapy (RT) results in permanent local control in the majority of patients.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 Whether adjuvant RT offers an advantage in survival or reduces deaths from prostate cancer compared to radiation delivered at the time of prostate-specific antigen (PSA) recurrence remains unknown. The majority of studies, which address this issue, are small, retrospective and suffer from short follow-up. The only published randomized trials report an advantage for early RT in terms of local control and recurrence-free survival, but follow-up is too short to address the issues of cause-specific and overall survival.2, 18, 19

Late recurrences of prostate cancer are a well-documented phenomenon. Few series describing the results of adjuvant RT report results beyond 5 years. Long-term data, even of a retrospective nature, might help to better guide physicians in the management of patients at high risk for local failure after RP, as well as provide information on patterns of recurrence, which would be useful in the design of future clinical trials. Herein, we describe long-term results of our series of patients with pathologic stage T3/4 prostate cancer, originally reported in 1987 and 1990,1, 20 who now have up to 30 years of follow-up after treatment for their disease with either surgery alone or surgery plus adjuvant RT.

Materials and methods

Patient selection

From 1970 to 1983, 319 patients with newly diagnosed adenocarcinoma of the prostate underwent RP at Duke University Medical Center. Of these patients, 159 (50%) had histologically positive surgical margins, complete capsular penetration and/or seminal vesicle involvement. These patients form the basis for this analysis.

Of the 159 patients, 46 (30%) were referred for adjuvant RT and the remaining 113 (70%) were not. Referral for postoperative therapy was at the discretion of the attending urologist.

Preoperative evaluation generally consisted of a history and physical examination, blood work and radiographic studies, including acid and alkaline phosphatases, chest X-ray, intravenous pyelography, computed tomography of the pelvis, skeletal survey, radioisotope bone scan and lymphangiography. PSA was not available in this era. Patients were retrospectively assigned a clinical stage according to the American Joint Committee on Cancer System (4th edition).21

Postoperatively, pathology reports were reviewed to determine the extent and grade of cancer present. Only patients with positive surgical margins, capsule penetration and/or seminal vesicle invasion (pathologic stage T3/4) were included in the study. Gleason sums of 2–4, 5–7 and 8–10 correlated with well, moderate and poor differentiation, respectively.

Radiotherapy technique

The RT technique used has been described previously.1, 22 In brief, a four-field box technique (AP–PA, right and left lateral fields) was used most commonly. Usually, 45–50 Gy in daily doses of 1.8–2 Gy were delivered to the whole pelvis, followed by an additional 10–15 Gy to the prostate bed. In general, customized blocking was used to protect the small bowel, bladder and rectum.

Androgen deprivation therapy

Androgen deprivation therapy was used in the neoadjuvant and/or adjuvant setting. Patients received it at the discretion of their attending urologist. Preoperative androgen deprivation was given on a temporary basis, whereas postoperative treatment was either temporary or permanent.1, 22

Statistical analysis

Patients lost to follow-up were censored at the date of last contact. Local failure was defined as serial changes on rectal examination confirmed by biopsy. Distant metastases were detected by physical examination and/or radiographic evaluation. Initially, three categories of failure were scored: local, distant and local plus distant. Beginning in 1987, biochemical failure was added as a fourth category. This was defined as a rise in the PSA of 10% or more on two consecutive values at least 4 weeks apart. In addition to the patterns of failure, end points included overall survival, cancer-related and non-cancer-related deaths. Survival curves were calculated by the Kaplan–Meier method.23 Differences between curves were compared using the Cox–Mantel test.24

Results

The characteristics of the two patient populations are summarized in Table 1. In many respects, the two groups are similar. The median duration of follow-up was longer for the irradiated group, as the patients treated with surgery only had a shorter median survival than the patients receiving adjuvant RT (Figure 1). However, the median follow-up of the surviving patients in both groups is nearly identical (Table 1). Only one patient, in the surgery group, was lost to follow-up (at 3 years). A higher percentage of irradiated patients underwent lymph node dissection and were found to have nodal metastases. A much larger percentage of patients treated without radiation received androgen deprivation, which was given at the discretion of the attending urologist. Androgen deprivation was used in the neoadjuvant and/or adjuvant setting. Irradiated patients were more likely to have positive surgical margins, but there was no difference in the groups with respect to the presence of capsule penetration or seminal vesicle involvement. Irradiated patients were more likely to have an elevated preoperative acid phosphatase.

Table 1 Patient characteristics
Figure 1
figure1

Actuarial survival comparison of patients treated with surgery alone (solid line) vs those treated with surgery plus adjuvant postoperative RT (broken line).

Survival

Of the 113 patients treated with surgery alone, 104 (92%) have died. Fifty-nine (57%) of the deaths in this group were from prostate cancer. In the group treated with surgery and adjuvant RT, 35 of 46 (76%) patients have died, 18 (51%) from prostate cancer. The median time to death in the surgery-alone group was 10 vs 15 years in the adjuvant RT group (P=0.1). At 15 years, the actuarial survival in the surgery-alone group was 35 vs 52% for the patient receiving adjuvant RT (P=0.1) (Figure 1).

Considering only deaths owing to prostate cancer, the actuarial cause-specific survival at 15 years was 48% in the surgery-only group vs 63% in the irradiated patients (P=0.08) (Figure 2). The median time to death from prostate cancer in the surgery-alone group was 15 vs 20 years in the adjuvant RT group. Although these differences are not statistically significant, adjuvant RT appears to be associated with a 15% reduction in deaths from prostate cancer at 15 years. Late deaths from prostate cancer were common in both groups of patients. Of the 59 deaths from prostate cancer in the surgery-alone group, 28 (47%) occurred beyond 10 years and 13 (22%) occurred more than 15 years after treatment. Similarly, of the 18 deaths from prostate cancer in the adjuvant RT group, eight (44%) occurred beyond 10 years and four (22%) occurred more than 15 years after therapy.

Figure 2
figure2

Actuarial cause-specific survival of patients treated with surgery alone (solid line) vs those treated with surgery plus adjuvant postoperative RT (broken line).

In contrast to deaths from prostate cancer, late relapses were relatively less common in both groups of patients. The median time to relapse in the surgery-alone group was 7.5 vs 14.7 years in the adjuvant RT group. Of the 67 relapses in the surgery group, only six (9%) occurred beyond 10 years and only one (1%) recurred more than 15 years after treatment. Late relapses were more common in the group receiving adjuvant RT vs the surgery-only patients. In the group receiving adjuvant RT, 4/23 (17%) relapses occurred beyond 10 years and two (9%) occurred more than 15 years after treatment. The addition of adjuvant RT was associated with prolongation in the time to relapse, although this difference was not statistically significant (Figure 3).

Figure 3
figure3

Actuarial disease-free survival of patients treated with surgery alone (solid line) vs those treated with surgery plus adjuvant postoperative RT (broken line).

Timing and patterns of failure

In the group treated with RP alone, there were an equal number of local and distant failures (40 local, 42 distant). In contrast, the group receiving adjuvant RT had three times as many distant failures as local recurrences (five local, 16 distant). At 15 years, the actuarial local control rate for the patients treated with surgery alone was 53 vs 89% for the patients receiving adjuvant RT (P=0.001) (Figure 4). The median time to local failure has not been reached for either group. In the surgery-alone group, the actuarial freedom from distant failure rate at 15 years was 55% compared to 62% for the adjuvant RT group (P=0.7) (Figure 5). The median time to development of distant metastases has not been reached in either the surgery or adjuvant RT group. Reflecting the era in which these patients were treated, biochemical failure was the initial sign of recurrence in only 13 patients, seven in the surgery group and six in the surgery plus RT group.

Figure 4
figure4

Actuarial local control of patients treated with surgery alone (solid line) vs those treated with surgery plus adjuvant postoperative RT (broken line).

Figure 5
figure5

Actuarial freedom from distant metastases of patients treated with surgery alone (solid line) vs those treated with surgery plus adjuvant postoperative RT (broken line).

Late distant failures were relatively uncommon in both groups. In the surgery-only patients, 8/42 (19%) of distant failures occurred beyond 10 years and two (5%) occurred more than 15 years after treatment. In the group receiving adjuvant RT, late distant metastases were even less common. Only 1/16 (6%) distant metastasis in this group developed more than 10 years after treatment.

Late local recurrences were very uncommon in the surgery-only group, with none occurring more than 11 years after treatment. In contrast, a significant proportion of local failures in the adjuvant RT group occurred late. In this group, 2/5 (40%) of the local failures occurred more than 10 years after treatment, including one, which occurred at 20 years.

Table 2 demonstrates the patterns of failure following adjuvant RT on local and distant failure as a function of site of involvement with prostate cancer. Adjuvant RT was associated with a reduction in the risk of local recurrence in patients with seminal vesicle involvement by 32%, in patients with capsular penetration by 27% and by 23% in patients with positive margins. In contrast, adjuvant RT was associated with a reduction in distant metastases of only 2–4% in these same patient populations.

Table 2 Patterns of relapse after adjuvant RT as a function of site of involvement

Discussion

The present study, to our knowledge, reports the longest follow-up data on a group of patients treated with adjuvant RT after RP for pathologic stage T3 disease. In addition, a unique feature of the study is the completeness of the data set. Only one patient was lost to follow-up, and 138 of the remaining 158 (87%) have been followed until death. Thus, these data, although retrospective and therefore not definitive with respect to the role of adjuvant RT, may prove useful in guiding future clinical trial design.

Nevertheless, the study does have several weaknesses. Given the fact that the RT was not given according to the predetermined guidelines, no definite conclusions can be drawn regarding its values as an adjuvant to prostatectomy for patients with locally advanced prostate cancer. Similarly, because androgen deprivation therapy was used in a significant number of patients and in an uncontrolled manner, no definite conclusions may be drawn regarding its role in the treatment of this population of patients. Despite these drawbacks, the data do provide some insights into the timing and pattern of relapse in patients with locally advanced prostate cancer, and support the value of long-term data collection.

In this series, late recurrences were relatively uncommon. More than 80% of all recurrences, both local and distant, occurred within 10 years of treatment. Late recurrences were more commonly distant in the surgery-alone group, whereas late local failures were more frequent in the adjuvant RT group. This finding suggests that the burden of residual local disease tends to be greater than that of occult distant metastases in patients with pathologic T3 prostate cancer; thus, local recurrences tend to appear sooner. In addition, adjuvant RT, if unsuccessful in eradicating local residual tumor, merely delays local regrowth of cancer. The finding of such late local recurrences after adjuvant RT reinforces the need for long-term follow-up of these patients, and suggests the need for higher doses of radiation to achieve permanent local control (60 Gy). Alternatively, as these patients were treated using outdated RT techniques, it is possible that better results may be achieved using modern three-dimensional conformal or intensity-modulated RT approaches.

Adjuvant RT resulted in a significant improvement in local control and a trend toward reduction in deaths from prostate cancer. However, adjuvant RT was not associated with a reduction in distant metastases. Consequently, no improvement in overall survival could be demonstrated with the addition of RT. These findings are consistent with those of other retrospective studies reported in the literature.1, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 20, 22 Recently, a large randomized trial of more than 1000 patients was published with findings similar to ours, although follow-up to date is only 5 years.2 It is possible that with longer follow-up, a survival advantage attributed to the use of adjuvant RT will emerge. Two other large randomized trials have been published only in abstract form, and no survival data are available.18, 19 Thus, the present study is one of the few to shed light on the long-term outcome, which might be expected for patients receiving adjuvant RT after RP.

After RP, patients with seminal vesicle invasion, capsule penetration and/or positive surgical margins are at high risk for recurrence.2, 19, 25, 26, 27 In the present study, the patients who did not receive adjuvant RT had an actuarial risk of failure at 15 years of 70%. These failures were equally distributed between local and distant sites. Furthermore, the study suggests that patients treated surgically, and are found to have disease outside the prostate, are likely to live long enough to fail, as the median time to failure was 7.5 years, whereas the median survival was 10 years (Figure 3). In addition, the patients seem to remain at risk for failure indefinitely. Although infrequent, local recurrences occurred more than 10 years after surgery and distant metastases occurred more than 18 years postoperatively (Figures 4 and 5).

The high rate of distant metastases in this patient population is concerning. Adjuvant RT did not seem to reduce the incidence of distant metastases, suggesting that approximately half of these patients already had micrometastatic disease at the time of diagnosis. The role of systemic therapy, either in the form of androgen deprivation or chemotherapy, in this patient population remains to be defined.14, 28, 29, 30, 31, 32, 33 Long-term androgen deprivation therapy has been demonstrated to improve survival in other groups of prostate cancer patients at high risk for metastatic disease treated either with RT or RP.34, 35, 36 As androgen deprivation therapy, in the present study, was not given according to the predetermined written guidelines, its role cannot be definitively determined. It is possible, however, that the frequent use of adjuvant and/or neoadjuvant androgen deprivation therapy in the patients treated without RT altered the timing and pattern of recurrence in this group of patients. The fact that this group was relatively less likely to develop distant metastases than the adjuvant RT group may be a reflection of the efficacy of androgen deprivation therapy. Thus, the role of androgen deprivation therapy in pathologic stage T3/4 disease deserves further study.

The group of patients described in the present report were all diagnosed and treated initially in the era predating PSA. Thus, they likely had more extensive disease at the time of surgery than the typical patient presenting today, that is, most commonly with an elevated PSA and negative digital rectal exam. Patients diagnosed earlier in the course of their disease, yet who are found to have histologic evidence of local extension outside of the prostate, might be less likely to have occult metastases and more likely to benefit from adjuvant RT. The findings of the recently published randomized trial of adjuvant RT vs observation for patients with positive margins, capsule penetration and/or seminal vesicle involvement would support this hypothesis.2 In this randomized study, patients in the observation arm were four times more likely to have a locoregional than a distant failure. In contrast, the patients receiving immediate adjuvant RT were equally likely to have locoregional or distant failure. Compare this finding to the present study, in which the surgery-only arm had an equal incidence of local and distant failures, whereas the RT group had three times more distant than local failures. With longer follow-up of the randomized trial, it should become apparent whether early local intervention for pathologic stage T3 prostate cancer diagnosed in the PSA era would translate into improvement in survival.

Conclusion

Recurrences beyond 10 years after RP in this group of patients were relatively uncommon. Late local failures after adjuvant RT were a surprising finding, suggesting the need for higher doses of radiation in this setting. Reflecting the long natural history of prostate cancer after recurrence,37 deaths beyond 10 years from treatment were common. Despite its long natural history, death from prostate cancer was the most common cause of mortality in this population with pathologic stage T3/4 tumors, reflecting the need for more effective systemic therapy.

References

  1. 1

    Anscher MS, Prosnitz LR . Postoperative radiotherapy for patients with carcinoma of the prostate undergoing radical prostatectomy with positive surgical margins, seminal vesicle involvement and/or penetration through the capsule. J Urol 1987; 138: 1407–1412.

  2. 2

    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: 572–578.

  3. 3

    Catton C, Gospodarowicz M, Warde P, Panzarella T, Catton P, McLean M et al. Adjuvant and salvage radiation therapy after radical prostatectomy for adenocarcinoma of the prostate. Radiother Oncol 2001; 59: 51–60.

  4. 4

    Cheng WS, Frydenberg M, Bergstralh EJ, Larson-Keller JJ, Zincke H . Radical prostatectomy for pathologic stage C prostate cancer: influence of pathologic variables and adjuvant treatment on disease outcome. Urology 1993; 42: 283–291.

  5. 5

    Choo R, Hruby G, Hong J, Hong E, DeBoer G, Danjoux C et al. Positive resection margin and/or pathologic T3 adenocarcinoma of prostate with undetectable postoperative prostate-specific antigen after radical prostatectomy: to irradiate or not? Int J Radiat Oncol Biol Phys 2002; 52: 674–680.

  6. 6

    Hagan M, Zlotecki R, Medina C, Tercilla O, Rivera I, Wajsman Z . Comparison of adjuvant versus salvage radiotherapy policies for postprostatectomy radiotherapy. Int J Radiat Oncol Biol Phys 2004; 59: 329–340.

  7. 7

    Kalapurakal JA, Huang CF, Neriamparampil MM, Small Jr WJ, Pins MR, Mittal BB et al. Biochemical disease-free survival following adjuvant and salvage irradiation after radical prostatectomy. Int J Radiat Oncol Biol Phys 2002; 54: 1047–1054.

  8. 8

    Kamat AM, Babaian K, Cheung MR, Naya Y, Huang SH, Kuban D et al. Identification of factors predicting response to adjuvant radiation therapy in patients with positive margins after radical prostatectomy. J Urol 2003; 170: 1860–1863.

  9. 9

    Mayer R, Pummer K, Quehenberger F, Mayer E, Fink L, Hackl A . Postprostatectomy radiotherapy for high-risk prostate cancer. Urology 2002; 59: 732–739.

  10. 10

    Morris M, Dallow K, Zeitman A, Park J, Althausen A, Heney N et al. Adjuvant and salvage irradiation following radical prostatectomy for prostate cancer. Int J Radiat Oncol Biol Phys 1997; 38: 731–736.

  11. 11

    Nudell D, Grossfeld G, Weinberg V, Roach III M, Carroll P . Radiotherapy after radical prostatectomy: treatment outcomes and failure patterns. Urology 1999; 54: 1049–1057.

  12. 12

    Pacholke HD, Wajsman Z, Algood CB, Morris CG, Zlotecki RA . Postoperative adjuvant and salvage radiotherapy for prostate cancer: impact on freedom from biochemical relapse and survival. Urology 2004; 64: 982–986.

  13. 13

    Peschel R, Robnett T, Hesse D, King C, Ennis R, Schiff P et al. PSA based review of adjuvant and salvage radiation therapy vs observation in postoperative prostate cancer patients. Int J Cancer (Radiat Oncol Invest) 2000; 90: 29–36.

  14. 14

    Taylor N, Kelly JF, Kuban DA, Babaian RJ, Pisters LL, Pollack A . Adjuvant and salvage radiotherapy after radical prostatectomy for prostate cancer. Int J Radiat Oncol Biol Phys 2003; 56: 755–763.

  15. 15

    Tsien C, Griffith KA, Sandler HM, McLaughlin P, Sanda MG, Montie J et al. Long-term results of three-dimensional conformal adjuvant and salvage radiotherapy after radical prostatectomy. Urology 2003; 62: 93–98.

  16. 16

    Valicenti R, Gomella L, Ismail M, Mulholland S, Strup S, Petersen R et al. Durable efficacy of early postoperative radiation therapy for high-risk pT3N0 prostate cancer: the importance of radiation dose. Urology 1998; 52: 1034–1040.

  17. 17

    Vicini F, Ziaja E, Kestin L, Brabbins D, Stromberg J, Gonzalez J et al. Treatment outcome with adjuvant and salvage irradiation after radical prostatectomy for prostate cancer. Urology 1999; 54: 111–117.

  18. 18

    Wiegel T, Bottke D, Willich N, Piechota H-J, Souchon R, Sloeckle M et al. Phase III results of adjuvant radiotherapy (RT) versus ‘wait and see’ (WS) in patients with pT3 prostate cancer following radical prostatectomy (RP) (ARO96-02/AUO AP 09/95). J Clin Oncol 2005; 23: 381s.

  19. 19

    Swanson GP, Thompson IM, Tangen C, Miller G, Lucia MS, Troyer DA et al. Phase III randomized trial of adjuvant radiation therapy versus observation in patients with pathologic T3 prostate cancer (SWOG 8794). Int J Radiat Oncol Biol Phys 2005; 63: S1.

  20. 20

    Paulson DF, Moul JW, Robertson JE, Walther PJ . Postoperative radiotherapy of the prostate for patients undergoing radical prostatectomy with positive margins, seminal vesicle involvement and/or penetration through the capsule. J Urol 1990; 143: 1178–1182.

  21. 21

    American Joint Committee on Cancer Manual for Staging of Cancer. JB Lippincott Co: Philadelphia, 1992.

  22. 22

    Anscher M, Robertson C, Prosnitz L . Adjuvant radiotherapy for pathologic stage T3/4 adenocarcinoma of the prostate: 10 year update. Int J Radiat Oncol Biol Phys 1995; 33: 37–43.

  23. 23

    Kaplan EL, Meier P . Nonparametric estimations from incomplete observations. J Am Statist Assoc 1958; 53: 457–481.

  24. 24

    Cox D . Regression models and life tables. JR Stat Soc B 1972; 34: 187–202.

  25. 25

    Anscher MS, Prosnitz LR . Multivariate analysis of factors predicting local relapse after radical prostatectomy – possible indications for postoperative radiotherapy. Int J Radiat Oncol Biol Phys 1991; 21: 941–947.

  26. 26

    D’Amico AV, Whittington R, Malkowicz SB, Schultz D, Tomaszewski JE, Wein A . Prostate specific antigen outcome based on the extent of extracapsular extension and margin status in patients with seminal vesicle negative prostate carcinoma of Gleason score < or =7. Cancer 2000; 88: 2110–2115.

  27. 27

    Han M, Partin AW, Zahurak M, Piantadosi S, Epstein JI, Walsh PC . Biochemical (prostate specific antigen) recurrence probability following radical prostatectomy for clinically localized prostate cancer. J Urol 2003; 169: 517–523.

  28. 28

    Corn BW, Winter K, Pilepich MV . Does androgen suppression enhance the efficacy of postoperative irradiation? A secondary analysis of RTOG 85-31. Radiation Therapy Oncology Group. Urology 1999; 54: 495–502.

  29. 29

    Eulau SM, Tate DJ, Stamey TA, Bagshaw MA, Hancock SL . Effect of combined transient androgen deprivation and irradiation following radical prostatectomy for prostatic cancer. Int J Radiat Oncol Biol Phys 1998; 41: 735–740.

  30. 30

    Katz MS, Zelefsky MJ, Venkatraman ES, Fuks Z, Hummer A, Leibel SA . Predictors of biochemical outcome with salvage conformal radiotherapy after radical prostatectomy for prostate cancer. J Clin Oncol 2003; 21: 483–489.

  31. 31

    King CR, Presti Jr JC, Gill H, Brooks J, Hancock SL . Radiotherapy after radical prostatectomy: does transient androgen suppression improve outcomes? Int J Radiat Oncol Biol Phys 2004; 59: 341–347.

  32. 32

    Song DY, Thompson TL, Ramakrishnan V, Harrison R, Bhavsar N, Onaodowan O et al. Salvage radiotherapy for rising or persistent PSA after radical prostatectomy. Urology 2002; 60: 281–287.

  33. 33

    Wiegel T, Bressel M, Carl UM . Adjuvant radiotherapy following radical prostatectomy – results of 56 patients. Eur J Cancer 1995; 31A: 5–11.

  34. 34

    Bolla M, Collette L, Blank L, Warde P, Dubois JB, Mirimanoff RO et al. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet 2002; 360: 103–106.

  35. 35

    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: 1781–1788.

  36. 36

    Pilepich MV, Winter K, Lawton CA, Krisch RE, Wolkov HB, Movsas B et al. Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma – long-term results of phase III RTOG 85-31. Int J Radiat Oncol Biol Phys 2005; 61: 1285–1290.

  37. 37

    Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC et al. Natural history of progression after PSA elevation following radical prostatectomy. JAMA 1999; 281: 1591–1597.

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Anscher, M., Clough, R., Robertson, C. et al. Timing and patterns of recurrences and deaths from prostate cancer following adjuvant pelvic radiotherapy for pathologic stage T3/4 adenocarcinoma of the prostate. Prostate Cancer Prostatic Dis 9, 254–260 (2006). https://doi.org/10.1038/sj.pcan.4500903

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Keywords

  • adjuvant radiotherapy
  • recurrence
  • survival
  • patterns of failure

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