Date Published: December 19, 2012
Publisher: Hindawi Publishing Corporation
Author(s): D. Milonas, G. Smailyte, M. Jievaltas.
Aim. The aim of this study is to present the oncologic outcomes and to determine the prognostic factors of overall survival (OS), cancer-specific survival (CSS), disease-progression-free survival (DPFS), and biochemical-progression-free survival (BPFS) after surgery for pT3 prostate cancer (PCa). Methods. Between 2002 and 2007, a pT3 stage after radical prostatectomy was detected in 182 patients at our institution. The Kaplan-Meier analysis was used to calculate OS, CSS, DPFS, and BPFS. Cox regression was used to identify predictive factors of survival. Results. pT3a was detected in 126 (69%) and pT3b in 56 (31%) of cases. Five-year OS, CSS, DPFS, and BPFS rates were 90.7%, 94%, 91.8%, and 48.4%, respectively. Survival was significantly different when comparing pT3a to pT3b groups. The 5-year OS, CSS, DPFS, and BPFS were 96% versus 72%, 98% versus 77%, 97.3% versus 79.3%, and 60% versus 24.2%, respectively. Specimen Gleason score was the most significant predictor of OS, CSS, DPFS, and BPFS. The risk of death increased up to 3-fold when a Gleason score 8–10 was present at the final pathology. Conclusions. Radical prostatectomy may offer very good CSS, OS, DPFS, and BPFS rates in pT3a PCa. However, outcomes in patients with pT3b or specimen Gleason ≥8 were significantly worse, suggesting the need for multimodality treatment in those cases.
During the last decade, the definition of the optimal treatment in high-risk prostate cancer (PCa) has been among the topics that are of most interest to the urological community, but consensus in this field is still not reached. Up until a decade ago, most T3 PCa patients underwent radiotherapy (RT) or androgen deprivation therapy (ADT) or a combination of both, while only about 36% were initially treated by surgery . Recent publications have revealed that in selected cases of locally advanced and high-grade tumours, surgery as monotherapy or as part of a multimodality treatment may be used instead of RT . The high-risk PCa population, usually described as having prostate specific antigen (PSA) >20 ng/mL, biopsy Gleason score ≥8, or an advanced clinical stage (T3a-b) , is however not homogeneous. Recent studies have shown that treatment outcomes can vary widely, depending on whether patients present with only one or rather a combination of those high-risk factors, with the latter patients having the worst outcomes [4–7]. It is still unclear which patients, according to the accepted predictors of aggressive disease behaviour, are the best candidates for surgery, mostly due to the lack of data on long-term oncologic outcomes and randomized clinical trials. According to the European Association of Urology guidelines, surgery is optional in patients presenting with cT3a, Gleason score 8–10, or PSA >20 ng/mL and life expectancy of more than 10 years . Even in highly selected patients with cT3b or cN1 PCa, surgery may be offered as part of a multimodality approach . We believe that radical prostatectomy is indeed an appropriate treatment for more aggressive PCa, but data for confirming that are still insufficient.
During the period 2002–2007, 840 radical retropubic prostatectomies (RRP) were performed in our tertiary referral institution. 192 of them had pathological stage T3 (22.9%). Ten patients were lost for additional followup. Final analysis was carried out using the data of 182 patients with complete followup. No patients received neoadjuvant treatment. The last PSA before biopsy was used for analysis.
An overview of the patients’ preoperative and postoperative parameters is shown in Table 1. The median followup was 54 months (range 6–96). 5-year rates for OS, CSS, DPFS, and BPFS in our study cohort were 90.7%, 94%, 91.8%, and, 48.4%, respectively. Cox regression analysis revealed that from all parameters (age, biopsy and surgery Gleason score, surgical margin and lymph node status, pathological stage, and preoperative PSA level) only pathological stage and postoperative Gleason score had an impact on overall mortality and disease progression (Table 2). The Gleason score also has the strongest impact on CSS. According to Cox regression analysis, there were no other parameters influencing cancer specific mortality (Table 2). Pathological stage, lymph node status and postoperative Gleason score were the strongest prognostic factors for biochemical disease progression (Table 2).
During the last decade, the discussion about the role of surgery in locally advanced PCa became increasingly active. Before that time, treatment of locally advanced PCa was mostly in hands of radiation oncologists . Such discussion became possible for several reasons: successful treatment of high-risk PCa with RT monotherapy requires high radiation doses (74–80 Gy), leading to higher rates of adverse events. On the other hand, recent studies [2, 9–12] demonstrate outcomes after surgery which can be compared with radiation therapy +/− ADT. Our single center study shows that surgical treatment may indeed be a reasonable treatment option in locally advanced PCa with 90.7% OS and 94% CSS at the 5-year follow-up mark. Surgery in pT3a PCa, independently of cancer differentiation and PSA level demonstrated significantly higher 5-year OS, CSS, DPFS, and BPFS rates when compared to pT3b disease (96% versus 72%, 98% versus 77%, 97.3% versus 79.3%, and 60% versus 24.2%, resp.). The survival rates of the pT3a patients in our study are similar to those reported by Hsu et al. in a study of 200 patients with unilateral cT3a treated by surgery. They also showed that progression-free survival rates of patients with pT3a PCa did not differ significantly from those with pT2 disease . Some other authors have also reported their outcomes of surgical treatment for T3 PCa. Summarizing those results, 5-year CSS and OS rates varied from 85 to 100% and from 75 to 98%, respectively [9–12]. Direct comparison between the outcomes of surgery and radiation is inadequate because of inherent selection biases, Gleason score upgrading, or stage migration after surgery. Nevertheless, this issue could be partially solved using data from the RTOG trials which compared RT to a combined approach using RT and ADT . In a review of those RTOG trials, different PCa risk groups were identified with group 2 (Gleason ≤6, T3Nx-N1 or Gleason 7, T1-2Nx) and group 3 (Gleason 7, T3Nx-N1 or Gleason ≥8, T1-2Nx) most closely corresponding with our study population. After radiation, the 5-year OS and CSS rates were 82% and 94% for group 2 and 68% and 83% for group 3, respectively . Outcomes from another long-term study comparing RT to RT with concomitant ADT were reported by Bolla et al. . In the EORTC trial, 412 patients with locally advanced PCa were treated with RT alone or in combination with ADT. Five-year OS and CSS rates were, respectively, 62 and 79% in the radiation-alone group. Better survival was reported in combination group: 78% and 94%, respectively. Our study data showed a comparable 94% 5-year CSS, similar to RT and ADT combination therapy.
Radical prostatectomy may offer very good CSS, OS, DPFS, and BPFS rates in pT3a PCa. However, outcomes in patients with pT3b or specimen Gleason ≥8 were significantly worse, suggesting the need for multimodality treatment in those cases.