Editing Prostate Cancer: Management of Locally Advanced Prostate Cancer (section)

==== Adjuvant radiation ====

===== Adjuvant radiation vs. observation (late salvage) =====
*3 RCTs have demonstrated improved biochemical recurrence–free and cancer-specific survival with the use of adjuvant radiation compared to observation for locally advanced/positive margin disease:

====== Southwest Oncology Group (SWOG) 8794 ======
* Initiated in 1987
* Population: 431 men with pT3 prostate cancer and/or positive surgical margins; ≈two thirds had undetectable PSA at randomization.
* Randomized to adjuvant RT vs. observation
* Results:
** Median follow-up of 12.5 months
** Median metastasis-free survival was significantly longer in the adjuvant radiation therapy arm compared to the salvage group (14.7 vs.12.9 years) in the salvage group.
** Overall survival was significantly longer in the adjuvant therapy group compared to the salvage arm (15.2 vs. 13.3 years). The number of men with pathologic T3 disease who must be treated with adjuvant radiotherapy to prevent 1 death at a median follow-up of 12.6 years was 9.1 patients.
* Interpretation: Adjuvant radiotherapy within 18 weeks after radical prostatectomy in patients with T3N0M0 prostate cancer significantly reduces the risk for PSA recurrence, metastasis, and need for hormonal therapy and increases overall survival.
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3510761/ Thompson, Ian M., et al.] "Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: long-term followup of a randomized clinical trial." ''The Journal of urology'' 181.3 (2009): 956-962.

====== European Organization for Research and Treatment of Cancer (EORTC) 22911 ======
* Initiated in 1992
* Population: 1005 men with pT3 prostate cancer and/or positive surgical margins
* Randomized to adjuvant RT vs. observation
* Results:
** Biochemical progression–free survival rate was improved by 21% at 5-years in the adjuvant radiation arm (74% adjuvant vs. 53% salvage arm)
** Clinical progression–free survival, defined as no evidence of clinical, sonographic, radiographic, or scintigraphic recurrence, was improved in the adjuvant radiation group compared to the salvage group, as was locoregional failure at 5 years, which was significantly lower in the adjuvant radiation group and 5.4% versus 15.4% in the salvage group.
** No difference in overall survival
** Bolla, Michel, et al. "Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: long-term results of a randomised controlled trial (EORTC trial 22911)." The Lancet 380.9858 (2012): 2018-2027. <nowiki>https://www.ncbi.nlm.nih.gov/pubmed/23084481</nowiki> [Original publication 2005]
** Secondary analyses of EORTC 22911 support the role of immediate RT in the specific subset with positive surgical margin (Van der Kwast et al, 2007). The treatment benefit on biochemical-free survival of adjuvant RT was primarily seen in patients with positive surgical margins (HR 0.38, P < .0001), whereas no benefit was observed in those with negative margins independent of other risk factors.

====== ARO 96-02 ======
* German study
* Population: 368 patients with pT3 or pT4 but without nodal metastatic disease
* Randomized to adjuvant RT vs. observation
** A major difference in this trial from the previous two is that all patients had an undetectable PSA level before randomization. Patients in the salvage group underwent salvage therapy with radiation and/or hormone therapy on recurrence.
* Results:
** Biochemical progression–free survival rate was improved by 21% at 10-years in the adjuvant arm (56% adjuvant vs. 35% salvage) [2014 update, original publication 2009]
** No improvement in metastasis-free or overall survival
* Wiegel, Thomas, et al. "Adjuvant radiotherapy versus wait-and-see after radical prostatectomy: 10-year follow-up of the ARO 96–02/AUO AP 09/95 trial." European urology 66.2 (2014): 243-250. <nowiki>https://www.ncbi.nlm.nih.gov/pubmed/24680359</nowiki> [Original publication 2009]

====== Systematic review and MA of 3 trials ======
* '''Immediate RT after RP reduces the risk of recurrence in patients with aggressive PCa'''. However, immediate postoperative RT is associated with an increased risk of acute and late side effects ranging from 15-35% and 2-8%, respectively.