Toxicity and Patient-Reported Outcomes of a Phase 2 Randomized Trial of Prostate and Pelvic Lymph Node Versus Prostate only Radiotherapy in Advanced Localised Prostate Cancer (PIVOTAL)

Abstract

Purpose To establish the toxicity profile of high-dose pelvic lymph node intensity-modulated radiation therapy (IMRT) and to assess whether it is safely deliverable at multiple centers. Methods and Materials In this phase 2 noncomparative multicenter trial, 124 patients with locally advanced, high-risk prostate cancer were randomized between prostate-only IMRT (PO) (74 Gy/37 fractions) and prostate and pelvic lymph node IMRT (P&P; 74 Gy/37 fractions to prostate, 60 Gy/37 fractions to pelvis). The primary endpoint was acute lower gastrointestinal (GI) Radiation Therapy Oncology Group (RTOG) toxicity at week 18, aiming to exclude a grade 2 or greater (G2+) toxicity-free rate of 80% in the P&P group. Key secondary endpoints included patient-reported outcomes and late toxicity. Results One hundred twenty-four participants were randomized (62 PO, 62 P&P) from May 2011 to March 2013. Median follow-up was 37.6 months (interquartile range [IQR], 35.4-38.9 months). Participants had a median age of 69 years (IQR, 64-74 years) and median diagnostic prostate-specific androgen level of 21.6 ng/mL (IQR, 11.8-35.1 ng/mL). At week 18, G2+ lower GI toxicity-free rates were 59 of 61 (96.7%; 90% confidence interval [CI], 90.0-99.4) for the PO group and 59 of 62 (95.2%; 90% CI, 88.0-98.7) for the P&P group. Patients in both groups reported similarly low Inflammatory Bowel Disease Questionnaire symptoms and Vaizey incontinence scores. The largest difference occurred at week 6 with 4 of 61 (7%) and 16 of 61 (26%) PO and P&P patients, respectively, experiencing G2+ toxicity. At 2 years, the cumulative proportion of RTOG G2+ GI toxicity was 16.9% (95% CI, 8.9%-30.9%) for the PO group and 24.0% (95% CI, 8.4%-57.9%) for the P&P group; in addition, RTOG G2+ bladder toxicity was 5.1% (95% CI, 1.7%-14.9%) for the PO group and 5.6% (95% CI, 1.8%-16.7%) for the P&P group. Conclusions PIVOTAL demonstrated that high-dose pelvic lymph node IMRT can be delivered at multiple centers with a modest side effect profile. Although safety data from the present study are encouraging, the impact of P&P IMRT on disease control remains to be established.

IMPT versus VMAT for Pelvic Nodal Irradiation in Prostate Cancer: A Dosimetric Comparison

“…The increase in toxicity with elective nodal coverage compared with prostate-only coverage was mild to moderate. Patients receiving elective nodal coverage had an approximately 20% greater rate of acute, grade 2 gastrointestinal toxicity [10]. Figure 1.…”

Individualized Dose-Escalation of HDR Prostate Brachytherapy Implant to Decrease Required External Beam Radiation Dose: A Retrospective Feasibility Study

“…For patients with extracapsular extension or those in whom pelvic nodal irradiation is desired (noting that the role for pelvis irradiation is still unclear),24, 25, 26, 27 a lower EBRT dose may affect the effective treatment of extraprostatic disease. Therefore, these patients may need to be excluded from studies looking to minimize EBRT dose by increasing HDR-BT dose.…”

Stereotactic Body Radiotherapy for High-Risk Prostate Cancer: A Systematic Review

“…Further evidence comes from several small single-arm prospective and retrospective cohorts [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ]. One particular question that needs to be addressed, with respect to safety and efficacy of SBRT use in HR patients, is the necessity for and feasibility of elective pelvic nodal irradiation [ 52 , 53 ]. Therefore, we conducted this systematic review to shed more light on the value of SBRT in patients with HR PCA.…”