Prostate Cancer Treatment-Related Toxicity: Comparison between 3D-Conformal Radiation Therapy (3D-CRT) and Volumetric Modulated Arc Therapy (VMAT) Techniques.

Objective: This paper illustrates the results of a mono-institutional registry trial, aimed to test whether gastrointestinal (GI) and genitourinary (GU) toxicity rates were lower in localized prostate cancer patients treated with image-guided volumetric modulated arc therapy (IG-VMAT) compared to those treated with IG-3D conformal radiation therapy (IG-3DCRT). Materials and Methods: Histologically proven prostate cancer patients with organ-confined disease, treated between October 2008 and September 2014 with moderately hypofractionated radiotherapy, were reviewed. Fiducial markers were placed in the prostate gland by transrectal ultrasound guide. The prescribed total dose was 70 Gy in 28 fractions. The mean and median dose volume constraints for bladder and rectum as well as total volume of treatment were analyzed as potentially prognostic factors influencing toxicity. The Kaplan−Meier method was applied to calculate survival. Results: Overall, 83 consecutive patients were included. Forty-two (50.6%) patients were treated with 3D-CRT and 41 (49.4%) with the VMAT technique. The median follow-up for toxicity was 77.26 months for the whole cohort. The VMAT allowed for a dose reduction to the rectum and bladder for the large majority of the considered parameters; nonetheless, the only parameter correlated with a clinical outcome was a rectal dose limit V66 > 8.5% for late GI toxicity G ≥ 2 (p = 0.045). Rates of G ≥ 2 toxicities were low among the whole cohort of these patients treated with IGRT. The analysis for rectum dose volume histograms (DVHs) showed that a severe (grade ≥ 2) late GI toxicity was related with the rectal dose limit V66 > 8.5% (p = 0.045). Conclusions: This study shows that moderate hypofractionation is feasible and safe in patients with intermediate and high-risk prostate cancer. Daily IGRT may decrease acute and late toxicity to organs at risk and improve clinical benefit and disease control rate, cutting down the risk of PTV geographical missing. The adoption of VMAT allows for promising results in terms of OAR sparing and a reduction in toxicity that, also given the small sample, did not reach statistical significance.

Accurate prediction of long-term risk of biochemical failure after salvage radiotherapy including the impact of pelvic node irradiation.

BACKGROUND AND PURPOSE: Explainable models of long-term risk of biochemical failure (BF) after post-prostatectomy salvage radiotherapy (SRT) are lacking. A previously introduced radiobiology-based formula was adapted to incorporate the impact of pelvic nodes irradiation (PNI). MATERIALS AND METHODS: The risk of post-SRT BF may be expressed by a Poisson-based equation including pre-SRT PSA, the radiosensitivity α, the clonogen density C, the prescribed dose (in terms of EQD2, α/ß = 1.5 Gy) and a factor (1-BxλxPSA) accounting for clonogens outside the irradiated volume, being λ the recovery due to PNI. Data of 795 pT2-pT3, pN0/pN1/pNx (n = 627/94/74) patients with follow-up ≥ 5 years and pre-RT PSA ≤ 2 ng/mL were randomly split into training (n = 528) and validation (n = 267) cohorts; the training cohort data were fitted by the least square method. Separate fits were performed for different risk groups. Model performances were assessed by calibration plots and tested in the validation group. RESULTS: The median follow-up was 8.5y, median pre-SRT PSA and EQD2 were 0.43 ng/mL and 71.3 Gy respectively; 331/795 pts received PNI. The most clinically significant prognostic grouping was pT3b and/or ISUP4-5 versus pT2/3a and ISUP1-3. Best-fit parameters were αeff = 0.26/0.23 Gy-1, C = 107/107, B = 0.40/0.97, λ = 0.87/0.41 for low/high-risk group. Performances were confirmed in the validation group (slope = 0.89,R2 = 0.85). Results suggested optimal SRT dose at 70-74 Gy. The estimated reduction of post-SRT BF due to PNI at these dose values was > 5 % for PSA > 1/>0.15 ng/mL for low/high-risk patients, being > 10 % for high-risk patients with pre-SRT PSA > 0.25 ng/mL. CONCLUSION: An explainable one-size-fits-all equation satisfactorily predicts long-term risk of post-SRT BF. The model was independently validated. A calculator tool was made available.

Multiparametric magnetic resonance imaging versus Partin tables and the Memorial Sloan-Kettering cancer center nomogram in risk stratification of patients with prostate cancer referred to external beam radiation therapy.

PURPOSE: To evaluate the agreement between multiparametric Magnetic Resonance Imaging (mpMRI), Partin tables (PT) and the Memorial Sloan Kettering Cancer Center nomogram (MSKCCn) in assessing risk category in prostate cancer (PCa) patients referred to External Beam Radiotherapy (EBRT). MATERIALS AND METHODS: In this bicentric study, we prospectively enrolled 80 PCa patients who underwent pre-EBRT mpMRI on a 3.0T magnet with a multiparametric protocol including high-resolution, multiplanar T2-weighted sequences, diffusion-weighted imaging and dynamic contrast-enhanced imaging. National comprehensive cancer network risk categories were assessed using prostate-specific-antigen level, Gleason score and the T-stage as defined by mpMRI or nomograms. Cohen's kappa statistic was used to calculate the agreement between mpMRI and nomograms in assessing the T-stage (organ-confined (OC) vs. non-organ-confined (nOC) disease) and risk category (≤ low risk vs. intermediate risk vs. ≥ high risk). RESULTS: mpMRI showed poor agreement with PT and MSKCCn in assessing nOC versus OC (k = 0.16 for both), translating into an mpMRI-induced reclassification of PT- and MSKCCn-related risk category in 36.3% (k = 0.43) and 41.3% (k = 0.31) of cases, respectively, with most changes occurring towards intermediate risk category. CONCLUSIONS: mpMRI showed low agreement with nomograms as a tool to stratify PCa risk, leading to significant risk reclassification. Assuming that mpMRI is a more reliable surrogate standard of reference for pathology, this technique should refine or replace nomograms in risk classification before EBRT.

Can multiparametric MRI replace Roach equations in staging prostate cancer before external beam radiation therapy?

PURPOSE: To investigate the agreement between Roach equations (RE) and multiparametric magnetic resonance imaging (mpMRI) in assessing the T-stage of prostate cancer (PCa). MATERIALS AND METHODS: Seventy-three patients with biopsy-proven PCa and previous RE assessment prospectively underwent mpMRI on a 3.0T magnet before external beam radiation therapy (EBRT). Using Cohen's kappa statistic, we assessed the agreement between RE and mpMRI in defining the T-stage (≥T3 vs.T≤2) and risk category according to the National comprehensive cancer network criteria (≤intermediate vs. ≥high). We also calculated sensitivity and specificity for ≥T3 stage in an additional group of thirty-seven patients with post-prostatectomy histological examination (mpMRI validation group). RESULTS: The agreement between RE and mpMRI in assessing the T stage and risk category was moderate (k=0.53 and 0.56, respectively). mpMRI changed the T stage and risk category in 21.9% (95%C.I. 13.4-33-4) and 20.5% (95%C.I. 12.3-31.9), respectively, prevalently downstaging PCa compared to RE. Sensitivity and specificity for ≥T3 stage in the mpMRI validation group were 81.8% (95%C.I. 65.1-91.9) and 88.5% (72.8-96.1). CONCLUSION: RE and mpMRI show moderate agreement only in assessing the T-stage of PCa, translating into an mpMRI-induced change in risk assessment in about one fifth of patients. As supported by high sensitivity/specificity for ≥T3 stage in the validation group, the discrepancy we found is in favour of mpMRI as a tool to stage PCa before ERBT.

Impact of multiparametric magnetic resonance imaging on risk group assessment of patients with prostate cancer addressed to external beam radiation therapy.

PURPOSE: To investigate the impact of multiparametric magnetic resonance imaging (mpMRI) on risk group assessment of patients with prostate cancer (PCa) initially addressed to external beam radiation therapy (EBRT). MATERIALS AND METHODS: We prospectively performed mpMRI (3.0Tsystem) in 44 patients addressed to EBRT, using a multiparametric protocol (high-resolution multiplanar T2-weighted, diffusion-weighted and dynamic contrast-enhanced imaging). Risk group was assessed in accordance with the National comprehensive cancer network (NCCN) categories, by combining prostate-specific-antigen level, Gleason score and the T-stage as established by digital rectal examination (clinical risk assessment; c-RA) versus mpMRI (mpMRI-risk assessment; mpMRI-RA). The agreement between c-RA and mpMRI-RA was investigated using Cohen's kappa. RESULTS: Patients were included in very low/low risk, intermediate risk, high risk, very high risk and metastatic NCCN categories in 10 (22.7%), 18 (40.9%), 15 (34.1%), 1 (2.3%) and 0 cases using c-RA vs. 8 (18.2%), 14 (31.8%), 14 (31.8%), 4 (9.1%) and 4 (9.1%) cases using mpMRI-RA, respectively, with only moderate agreement (k=0.43). mpMRI-RA determined risk downgrading in 2/44 patients (4.5%), and risk upgrading in 16/44 patients (36.3%). After mpMRI, EBRT remained indicated in all patients. CONCLUSION: mpMRI changed clinical risk stratification in about 41% of patients with PCa, with potential impact on EBRT planning.