Research Article: The Role of Adjuvant Hormonal Treatment after Surgery for Localized High-Risk Prostate Cancer: Results of a Matched Multiinstitutional Analysis

Date Published: January 31, 2012

Publisher: Hindawi Publishing Corporation

Author(s): Maria Schubert, Steven Joniau, Paolo Gontero, Susanne Kneitz, Claus-Jürgen Scholz, Burkhard Kneitz, Alberto Briganti, R. Jeffrey Karnes, Bertrand Tombal, Jochen Walz, Chao-Yu Hsu, Giansilvio Marchioro, Pia Bader, Chris Bangma, Detlef Frohneberg, Markus Graefen, Fritz Schröder, Paul van Cangh, Hein van Poppel, Martin Spahn.


Introduction. To assess the role of adjuvant androgen deprivation therapy (ADT) in high-risk prostate cancer patients (PCa) after surgery.
Materials and Methods. The analysis case matched 172 high-risk PCa patients with positive section margins or non-organ confined disease and negative lymph nodes to receive adjuvant ADT (group 1, n = 86) or no adjuvant ADT (group 2, n = 86). Results. Only 11.6% of the patients died, 2.3% PCa related. Estimated 5–10-year clinical progression-free survival was 96.9% (94.3%) for group 1 and 73.7% (67.0%) for group 2, respectively. Subgroup analysis identified men with T2/T3a tumors at low-risk and T3b margins positive disease at higher risk for progression. Conclusion. Patients with T2/T3a tumors are at low-risk for metastatic disease and cancer-related death and do not need adjuvant ADT. We identified men with T3b margin positive disease at highest risk for clinical progression. These patients benefit from immediate adjuvant ADT.

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Patients with high-risk localized prostate cancer (PCa) based on either PSA >20 ng/mL, Gleason score (GS) ≥8, or an advanced clinical stage have a risk of biochemical failure of up to 70% with surgery alone [1–5]. This has raised the question on the need of adjuvant treatments including androgen deprivation, radiation, and chemotherapy. Adjuvant androgen deprivation therapy (ADT) has shown significant improvement in disease-free survival for men with high-risk PCa treated with definitive radiation therapy and a survival benefit for men with GS 8–10 [6, 7]. For patients treated with radical prostatectomy (RP) the role of adjuvant ADT is still controversial. In a small prospective, randomized trial a survival benefit with adjuvant ADT in patients with lymph node positive disease was shown [8]. Two retrospective studies have reported a survival advantage for immediate ADT in patients with locally advanced disease [9, 10]. For patients with pT3N0M0 PCa Thompson et al. recently reported improved metastasis-free and overall survival (OS) with adjuvant radiation therapy when compared to observation [11]. Current guidelines therefore recommend adjuvant radiation for these patients [12, 13]. However, the results of the ADT-alone control arm of the SWOG study S9921 reported on excellent 5-year progression-free (92.5%) and OS rates (95.9%) for men with high-risk PCa treated with RP and adjuvant ADT over a two-year period [14]. These excellent results were seen despite a minority of patients receiving adjuvant radiation and therefore suggest there might be a role for adjuvant ADT in men with pT3 disease and/or positive surgical margin.

Out of 1413 patients 800 met the inclusion criteria. From these 86 were matched into each group. The homogeneity of both groups is shown in Table 1.

There is increasing evidence that surgery provides a reasonable treatment option for selected men with high-risk prostate cancer [1, 5, 15, 16]. The recently reported results of the control arm of the SWOG-study S9921 showed that the combination of surgery and combined adjuvant ADT is associated with favorable disease-free and overall survival of greater than 92% at 5 years of follow-up [14]. Our study results corroborate these better than expected survival rates even for a high-risk cohort with positive section margins or non-organ confined disease and negative lymph nodes (8-year PCSS 97.5% and OS 92.7%). The results reported here and in the S9921-trial together with the improved outcomes for the combination of radiation and ADT in men with high-risk prostate cancer support the use of a multimodal treatment including adjuvant ADT [7, 8, 17]. However, the survival rates reported in these trials reach up to 90% for PCSS and 76% for OS, indicating that what we currently define as “high-risk” disease group indeed is a heterogeneous cohort with better than expected outcomes. These limitations in risk assessment are also visible in the adjuvant radiation therapy (RT) trials. Although some differences exist among the inclusion criteria, these studies showed a benefit for immediate adjuvant radiation in terms of biochemical progression (hazard ratio 0.47, 95% CI: 0.4–0.56, P < 0.0001) [17]. But only the SWOG-study could show a significant improvement in metastasis-free and OS of 1.8 and 1.9 years, respectively [11]. Overtreatment is obvious from these RT trials: the number needed to treat was 12.2 to prevent metastasis in one patient at 12.6 years of follow-up and the number needed to treat was 9.1 to prevent one death at the same time. Therefore, Colette et al. tried to substratify the patients from EORTC-trial 22911 and identified men with positive section margins to be at higher risk for biochemical progression (relative risk reduction of 62% for irradiated men, HR 0.38) [18]. Our results indicate excellent outcomes for high-risk prostate cancer with positive section margins or non-organ confined disease but negative lymph nodes after surgery. Patients with T2/T3a tumors are at low risk for metastatic disease and cancer-related death even in case of positive section margins—adjuvant ADT therefore can be avoided in these patients. Pathological stage and section margin status allows us to identify men with T3b surgical margin positive disease at highest risk for clinical progression. These patients benefit from immediate adjuvant ADT. However, such risk stratification is limited and far away from personalized therapy. Research energy should be focused on the identification and validation of new molecular markers to identify lethal disease. We recently described a new biomarker to predict clinical recurrence in high-risk PCa patients [23].   Source: