Radical prostatectomy for pathologic stage C prostate cancer: Influence of pathologic variables and adjuvant treatment on disease outcome

The management of high-risk prostate cancer following radical prostatectomy remains a treatment dilemma. Multimodality approaches incorporating surgery, radiation therapy and systemic agents offer the hope of improved cure rates; however, most randomized studies to date are either immature or negative. The systemic treatment options best studied is androgen deprivation, which has been shown to demonstrate a survival advantage in patients with lymph node-positive disease. Systemic chemotherapy has demonstrated a modest survival advantage in androgen-independent disease. Current studies are exploring its role in the adjuvant and neo-adjuvant setting. Lastly, recent randomized trials have demonstrated a biochemical advantage to adjuvant radiation therapy, but it remains to be seen if this will translate to an improvement is survival end points or if salvage radiation therapy would be just as effective. In this update article, we review the use of external beam radiation therapy and systemic agents in combination with surgery for high-risk prostate cancer patients.

Section: Adjuvant Radiation Therapymentioning

confidence: 52%

Section: Adjuvant Radiation Therapymentioning

confidence: 98%

Adjuvant and salvage treatment options for patients with high-risk prostate cancer treated with radical prostatectomy

Kibel

Nelson

2007

“…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 followup 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.…”

Section: Discussionmentioning

confidence: 71%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Anscher

Clough

Robertson

et al. 2006

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 ¼ 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.

“…6 Another large cohort of patients with pathological stage T3 prostate cancer revealed 46% biochemical progression-free survival at 10 y. 8 The dilemma of effective treatment for locally advanced prostate cancer is complicated by the finding that 78% of the above-mentioned pT3 prostate cancers were clinical stage T2, suggesting that patients are not infrequently understaged.…”

Section: Introductionmentioning

confidence: 99%

Multimodality radiotherapy and androgen ablation in the treatment of clinically localized prostate cancer: early results in high risk patients

Coblentz

Bissonette

Williams

et al. 2002

In patients presenting with clinically localized prostate cancer, the risk of biochemical failure increases significantly with higher Gleason scores, prostate specific antigen (PSA) levels, and clinical stages. Current surgical and radiotherapeutic approaches appear to offer limited success in patients with highly adverse prognostic factors. In an attempt to improve on these outcomes, we have combined external beam radiotherapy (EBRT) with a brachytherapy (BT) boost and neo adjuvant and adjuvant androgen ablation in a population at significant risk of biochemical failure. Here we present early biochemical progression data for this approach. From October 1997 to July 1999, 72 men with a serum PSA 10 ng/ml or Gleason score 7 or clinical stage T2c (AJC/UICC 1992) underwent EBRT followed by palladium-103 BT. All patients underwent 8 months of combined androgen ablation with leuprolide and an oral antiandrogen beginning 3 months prior to initiation of EBRT. Patients were followed by PSA and digital rectal examination (DRE) at 3-month intervals and a chart review on all patients was carried out during July 2001. To allow comparisons to contemporary literature, Kaplan-Meier survival curves were generated utilizing three alternate definitions of biochemical recurrence: PSA > 0.2 ng/ml, PSA > 1.0 ng/ml, and the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus definition of three consecutive rising PSAs. Our results indicate that when PSA > 0.2 ng/ml was used to define biochemical progression, 88% (95% CI 80 -97) of patients remained free of disease at 24 months. When PSA > 1.0 ng/ml was used, 97% (CI 92 -100) of patients remained disease free at 24 months. ASTRO criteria yielded 90% (CI 82 -98) recurrence-free survival at 24 months. In conclusion, this very early report indicates that in patients who are at increased risk of biochemical failure, EBRT with a BT boost in conjunction with short-term androgen ablation offers potentially superior biochemical disease-free survival to contemporary alternative approaches in the literature. Clearly, longer followup is required to confirm the durability of this approach.