Local failure is a dominant mode of recurrence in locally advanced and clinical node positive prostate cancer patients treated with combined pelvic IMRT and androgen deprivation therapy

https://doi.org/10.1016/j.urolonc.2018.09.016Get rights and content

Highlights

  • The pattern of failure after EBRT/ADT was mainly seen locally in the primary tumor or distant spread alone or combined with local recurrence.

  • Patients with limited cN1 disease and treated with pelvic radiation had no isolated recurrence at this anatomic site.

  • Diagnostic MRI distinguished patients with high risk of relapse challenging the need for surgical lymph node staging in our study.

Abstract

Background

The recurrence patterns of high-risk, N1 prostate cancer after radiation therapy (RT) including the pelvic lymph nodes have not been fully investigated.

Material and methods

We have a prospective clinical study since 2004 that has followed 138 men with locally advanced prostate cancer (T1-T4N0-N1M0) treated with definitive RT encompassing the prostate and pelvic lymph nodes and long-term androgen deprivation therapy (ADT). Forty nine of the 52 patients that developed recurrence were imaged at biochemical failure to detect the site of recurrence.

Results

Imaging identified the site of recurrence in 46 patients. Twenty five patients had prostatic recurrence only, none had local lymph node recurrence only, 11 had distant metastases only, 7 had prostatic recurrence and distant metastases, 2 had prostatic recurrence, local nodal recurrence and distant metastases, and 1 had local nodal recurrence with distant metastases. The mean time to recurrence was 62 months for prostate only, 40 months for distant only and 50 months for prostate and distant recurrence. There was a 69% recurrence rate for patients with magnetic resonance imaging -detected N1 disease. There was significantly longer survival for patients with prostate recurrence only compared to patients with distant recurrence (P < 0.018). Five-year prostate cancer-specific survival were 85% for prostate only, 44% for distant only and 48% for prostate and distant recurrence (prostate only vs. distant only; P = 0.008, prostate only vs. prostate and distant; P = 0.018, distant vs. prostate and distant; P = 0.836).

Conclusions

The predominant recurrence pattern for high-risk, N1 prostate cancer was prostatic recurrence and distant spread after pelvic RT and androgen deprivation therapy. Our data argue for further local dose escalation and pelvic nodal radiation to prevent recurrence in these sites. Lymph node metastasis at initial staging with an magnetic resonance imaging was a strong predictor of recurrence and poor survival and may identify patients in need of more aggressive treatment.

Introduction

Optimal treatment of locally advanced, N1 prostate cancer has not been determined. The experience from extended lymphadenectomy suggests that for a subgroup of patients with limited positive pelvic lymph nodes (<3), irradiation of the pelvic lymphatic structures could translate into long-lasting disease control [1], [2]. Similarly, there are data that definitive radiation therapy (RT) and androgen deprivation therapy (ADT) in cN1 may be more beneficial than ADT alone [3], [4], [5], [6], [7], [8]. Previously, we reported favorable outcomes, particularly in N1 disease, in patients with locally advanced and/or N1 prostate cancer undergoing intensity-modulated RT (IMRT) combined with long-term ADT [9]. In this study, we present the pattern of recurrence as visualized by magnetic resonance imaging (MRI) at biochemical failure (BF) and survival of this cohort.

Section snippets

Study overview

Our IMRT-study [9] was a prospective, single-arm study initiated to determine patient-scored toxicity and survival for men with locoregional disease (cN1) that received pelvic nodal radiation and long-term ADT (≥6 months). In addition to International Union Against Cancer, (TNM/UICC) staging [10], the inclusion criteria were age <75 years, no previous invasive cancer, diagnosis no older than 6 months, pN1M0 or a calculated N+ risk ≥15% using the Memorial Sloan Kettering Cancer Center nomogram

Site of recurrence

Fig. 1 stratifies number and site of recurrence to N-staging from pathology and MRI. There is no difference in recurrence rate between patients with pN0 and pN1 (P = 0.34). However, there is a significantly higher recurrence rate for patients with mrN1 compared to mrN0 (P < 0.001). N1 does not predict site of recurrence. Three of the 52 patients had no imaging at BF and for 3 other patients the site of recurrence was undetected. Thus, the site of recurrence was detected in 46 patients (Fig. 2).

Discussion

This study reports the recurrence pattern for high-risk, locally advanced prostate cancer patients treated with definitive RT encompassing the prostate and pelvic lymph nodes and long-term ADT. To our knowledge, this is the first data on patterns of recurrence after definitive RT with a standardized treatment of pelvic lymph nodes and long-term ADT. From this study, we believe a few clinically relevant conclusions can be drawn.

Two recurrence sites predominated; prostatic recurrence and distant

Conclusion

In conclusion, this cohort of high-risk locally advanced prostate cancer patients had minimal lymph node recurrences, presumably due to nodal radiation, with prostatic recurrence and distant spread predominating. Our data argue for further dose escalation given the predominance of local recurrences. Unfortunately, metastatic disease still has high mortality, and alternative therapies should be explored for these patients.

Conflict of interest

None.

References (28)

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Funding: The generous support of the study through personal grants from the Olav Raagholt and Gerd Meidel Foundation and the Prostate Cancer Foundation-Norway is highly appreciated. Grant number 36719 PCFN and Raagholt Foundation personal grant (without number).

1

Author Contributions: These 2 authors (J.H. and K.H.) contributed equally to the writing of the manuscript. All authors read manuscript.

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