Post-prostatectomy Radiotherapy Research Articles

Comparison of Outcomes from Adjuvant Radiation Including Pelvic Lymph Nodes Versus Prostate Bed Only Radiation for Prostate Cancer after Prostatectomy and Interaction with Pelvic Lymph Node Dissection

For prostate cancer patients, adjuvant radiation after prostatectomy is considered for pathologic risk factors including positive margins, extension outside the prostatic capsule (extracapsular extension or ECE), and seminal vesicle invasion (SVI). Studies have shown improved biochemical progression free survival with adjuvant radiation therapy. However, the appropriate treatment volume has not been determined prospectively, so whether to add pelvic lymph nodes to the radiation field for high risk patients remains controversial. We studied the impact of adding pelvic lymph nodes to the treatment field in post-prostatectomy patients undergoing adjuvant radiation. We evaluated 25,784 non-metastatic prostate cancer patients who underwent prostatectomy followed by adjuvant radiation therapy from the National Cancer Database from 2004 to 2015. The data was managed and analyzed in SAS 9.4. Analysis was carried out using Kaplan-Meier survival analysis. Median follow-up was 67 months (41.3-96.1). Mean age at diagnosis was 61.2 years old. 10,233 patients received radiation to the prostate only, 9,891 received radiation to the prostate and pelvis, and 5,660 did not have radiation fields available. A total of 8,487 patients (32.9%) had ECE on pathology, 9,601 patients (37.1%) had SVI, and 3,571 (14.1%) had positive surgical margins; 19,210 patients (74.5%) had at least one of these risk factors. A total of 20,374 patients (79.4%) of patients had regional lymph nodes examined with a lymph node dissection.A total of 3,286 patients (16.1%) had positive lymph nodes on pathology.For all patients, there was increased hazard of death for those who received radiation to the prostate and pelvis versus prostate alone (HR = 1.21, p =0.05). When patients were stratified by risk factors, for patients with positive margins, ECE, SVI, or positive lymph nodes, radiation field size was not significantly associated with overall survival. Patients who did not have ECE, SVI, positive margins, or positive lymph nodes had an increased hazard of death with radiation to the prostate and pelvis versus prostate alone (HR 1.18, p = <0.0001). For patients on androgen deprivation therapy and patients who had not undergone pelvic lymph node dissection, there was also no significant change in overall survival with radiation field size. For all patients, there was increased hazard of death for those who received radiation to the prostate and pelvis versus prostate alone. This effect was still seen in patients without ECE, SVI, positive margins, or positive pelvic lymph nodes. In patients with ECE, SVI, positive margins, positive lymph nodes, on ADT, or patients who had not undergone pelvic lymph node dissection, no change in overall survival was correlated with radiation fields. This data does not support a benefit for post-prostatectomy radiation fields including pelvic lymph nodes. It is possible that with a longer follow-up, an overall survival benefit would be seen in specific subpopulations.

Dosimetric and volumetric effects in clinical target volume and organs at risk during postprostatectomy radiotherapy.

To assess the reproducibility of the dose-volume distribution of the initial simulation CT, generated using volumetric modulated arc therapy (VMAT) planning, during the radiotherapy of the prostatic bed based on weekly cone beam CTs (CBCT). Twenty-three patients, after radical prostatectomy were treated with adjuvant or salvage radiotherapy between July and December 2016 and considered for this evaluation. Weekly CBCT scans (n = 138) were imported into the treatment planning system, and the clinical tumor volume (CTV), the rectum and the bladder were contoured. The initially calculated dose distribution and the dose-volume histograms generated from weekly CBCTs were compared. The prostatic fossa dose coverage was assessed by the proportion of the CTV fully encompassed by the 95% and 98% isodose lines. Rectal and bladder volumes receiving 50, 60 and 65 Gy during the treatment were compared to the initial plan, with statistical significance determined using the one-sample t‑test. Marked variations in the total organ volume of the rectum and the bladder were observed. The correlation between rectum volume and V50 was not significant (p = 0.487), while the bladder volume and V50 demonstrated asignificant correlation. There was no correlation between urinary bladder volume and CTV. The change in rectal volume correlated significantly with CTV. The dose coverage (D98% and D95%) to the prostatic bed could be achieved for all patients due to the ventral shift in the volume differences of the rectum. Weekly CBCTs can be considered as adequate verification tools to assess the interfractional variability of the CTV and organs at risk. The proven volume changes in the urinary bladder and the rectum do not compromise the final delivered dose in the CTV.

Androgen deprivation therapy use with post-prostatectomy radiotherapy in the Prostate Cancer Outcomes Registry Victoria.

The aim of this study is to evaluate the use of androgen deprivation therapy (ADT) with post-prostatectomy radiotherapy (PPRT) in a population-based cohort of Australian men. This is a prospective cohort of men with localised prostate cancer captured in the Prostate Cancer Outcomes Registry Victoria (PCOR-Vic), who received PPRT between January 2010 and December 2015. The primary outcome was ADT use with PPRT. Multivariate logistic regressions were used to identify patient, tumour and institutional factors influencing ADT use. 485 men were included in this study - 115 (24%) had pT2 disease, 231 (48%) pT3a, 134 (28%) pT3b and 5 (1%) pT4. Eighteen (4%) men had ISUP grade 1 disease, 139 (29%) ISUP grade 2, 170 (35%) ISUP grade 3 and 158 (33%) ISUP grade 4/5, while 267 (64%) men had positive surgical margins. Median time from prostatectomy to PPRT was 8.1months (IQR=5.3-13.9). Sixty-six (14%) patients had ADT with PPRT. In multivariate analyses, men who had increased age (OR=1.06; 95% CI=1.01-1.11), seminal vesicle involvement (OR=3.81; 95% CI=1.63-8.91) and underwent treatment in regional centres (OR=2.17; 95% CI=1.08-4.33) were more likely to have ADT with PPRT. We reported that 14% of men treated with PPRT received ADT in a population-based cohort of Australian men, which was less than half of the proportion of ADT use with PPRT in the US. It will be of interest to evaluate the uptake of ADT with PPRT in the coming years following recent publications of level 1 evidence confirming overall survival benefits of ADT with PPRT.

Postprostatectomy radiation therapy for biochemically recurrent prostate cancer

Postprostatectomy radiation therapy for biochemically recurrent prostate cancer

P251 - What is the optimal field of post-prostatectomy radiation therapy? Long-term results from a multi-institutional study

P251 - What is the optimal field of post-prostatectomy radiation therapy? Long-term results from a multi-institutional study

Development and Validation of a 28-gene Hypoxia-related Prognostic Signature for Localized Prostate Cancer

BackgroundHypoxia is associated with a poor prognosis in prostate cancer. This work aimed to derive and validate a hypoxia-related mRNA signature for localized prostate cancer. MethodHypoxia genes were identified in vitro via RNA-sequencing and combined with in vivo gene co-expression analysis to generate a signature. The signature was independently validated in eleven prostate cancer cohorts and a bladder cancer phase III randomized trial of radiotherapy alone or with carbogen and nicotinamide (CON). ResultsA 28-gene signature was derived. Patients with high signature scores had poorer biochemical recurrence free survivals in six of eight independent cohorts of prostatectomy-treated patients (Log rank test P < .05), with borderline significances achieved in the other two (P < .1). The signature also predicted biochemical recurrence in patients receiving post-prostatectomy radiotherapy (n = 130, P = .007) or definitive radiotherapy alone (n = 248, P = .035). Lastly, the signature predicted metastasis events in a pooled cohort (n = 631, P = .002). Prognostic significance remained after adjusting for clinic-pathological factors and commercially available prognostic signatures. The signature predicted benefit from hypoxia-modifying therapy in bladder cancer patients (intervention-by-signature interaction test P = .0026), where carbogen and nicotinamide was associated with improved survival only in hypoxic tumours. ConclusionA 28-gene hypoxia signature has strong and independent prognostic value for prostate cancer patients.

Androgen deprivation therapy during and after post-prostatectomy radiotherapy in patients with prostate cancer: a case control study

BackgroundHere we assessed the influence of androgen deprivation therapy (ADT) during and/or after post-prostatectomy radiotherapy (RT) on biochemical recurrence (BCR) and radiographic progression in patients with prostate cancer.MethodsPatients with prostate cancer who underwent post-prostatectomy RT were analyzed. BCR and radiographic progression after RT were compared according to the concurrent or salvage ADT. Cox regression analyses were used to identify risk factors for BCR and radiographic progression.ResultsOf the 227 patients who underwent post-prostatectomy RT, 95 (41.9%) received concurrent ADT for a median of 17.0 months. Despite more aggressive disease characteristics in the concurrent ADT group than in the RT-only group, the former had a better 5-year BCR-free survival rate than the latter (66.1 vs. 53.9%; p = 0.016), whereas the radiographic progression rate was not significantly different between two groups. On the other hand, salvage ADT after post-RT BCR significantly delayed radiographic progression (5-year radiographic progression-free survival; 75.2 vs. 44.5%; p = 0.002).ConclusionsConcurrent ADT improved BCR-free survival, and salvage ADT after post-RT BCR improved radiographic progression-free survival. To maximize the oncological benefit, ADT of sufficient duration should be implemented.

Does rectum and bladder dose vary during the course of image-guided radiotherapy in the postprostatectomy setting?

To assess the variations in actual doses delivered to the rectum and bladder in the course of postprostatectomy radiotherapy using kilovoltage-cone-beam computed tomography datasets acquired during image-guided radiotherapy. Twenty consecutive patients treated with intensity-modulated or intensity-modulated arc therapy to the prostate bed were retrospectively evaluated. Both the planning tomography and kilovoltage-cone-beam computed tomography were acquired with an empty rectum and a half-full bladder. Target localization was performed on the basis of soft tissue matching using cone-beam computed tomography scans before each treatment fraction. A total of 16 cone-beam computed tomography scans per patient (acquired at the first 5 fractions and twice weekly thereafter) were used for the assessments. The bladder and rectum were re-contoured offline on each cone-beam computed tomography scan by a single physician, and the delivered doses were recalculated. The variations in certain dose-volume parameters for the rectum and bladder (BD2cc, RD 2cc, V40%, V50%, V60%, V65%) were analyzed using the paired t test. Most of the dose volume variations for rectum and bladder were significantly higher than predicted (P <0.05) for the 320 kilovoltage-cone-beam computed tomography sets, except for the doses received by 2 cc of the bladder and V50 and V60 of the rectum. The dose-volume parameters of the bladder did not meet our criteria of V65 ≤25% and V40 ≤50% in 10% and 20% of the patients, respectively. None of the dose-volume histograms showed rectal V65 ≥17%; however, the rectal V40 ≤35% dose constraint was not met in 11 patients. For all patients, the ANOVA test revealed no significant difference between the variations. Actual doses delivered during treatment were found to be higher than predicted, but the majority of calculated bladder and rectal doses remained in the limits of our plan acceptance criteria. Interfraction variability of the rectum and bladder is a major concern in the postprostatectomy radiotherapy setting, even when patients are instructed about rectal and bladder preparation before the radiotherapy course. Image guidance with cone-beam computed tomography at each treatment fraction may offer a viable tool to account for interfraction variations of the rectum and bladder throughout the treatment course.

Assessing the need for and the optimal duration of hormonal therapy in association with post-prostatectomy radiation therapy: Results from a multi-institutional study

Assessing the need for and the optimal duration of hormonal therapy in association with post-prostatectomy radiation therapy: Results from a multi-institutional study

What is the optimal field of post-prostatectomy radiation therapy? Long-term results from a multi-institutional study

What is the optimal field of post-prostatectomy radiation therapy? Long-term results from a multi-institutional study

Optimal timing of post-prostatectomy radiotherapy for prostate cancer with high-risk pathologic features: A multi-institutional analysis.

24 Background: The use of radical prostatectomy (RP) as initial treatment of high-risk/locally-advanced prostate cancer is increasing but patients (pts) with adverse pathologic features such as positive surgical margins or T3 disease have up to 70% recurrence risk. These high-risk pts may be managed with adjuvant radiotherapy (ART) or early salvage radiotherapy (ESRT). The optimal timing of post-operative radiotherapy is unclear. Methods: Individual data from 1566 consecutive pts with pT2N0M0/R1 or pT3N0M0/R0-1 disease who underwent post-prostatectomy ART or ESRT (1987-2013) at 10 academic centers were pooled. Post-irradiation freedom from biochemical failure (FFBF), freedom from distant metastases (FFDM), prostate-cancer specific survival (PCSS), and overall survival (OS) were compared using Kaplan-Meier and multivariate competing-risks regression (MVA) analyses. Propensity score (PS) matching was used to account for covariates potentially associated with treatment allocation. All outcomes were measured from the date of surgery to address lead time bias. Results: After PS-matching, median follow-up after surgery was 66 vs. 73 months for the ART and ESRT groups, respectively, and baseline characteristics were well-matched. ART was associated with higher FFBF (12-yr: 69% vs. 43%; log-rank P &lt; 0.0001), FFDM (12-yr: 95% vs. 85%; log-rank P = 0.03), PCSS (12-yr: 99% vs. 94%; log-rank P = 0.048), and OS (12-yr: 91% vs. 79%; log-rank P = 0.01). ART, lower Gleason score, lower T-stage, nodal irradiation, and postoperative androgen deprivation therapy were favorable prognostic features on MVA for BF. Sensitivity analysis demonstrated that the decreased risk of BF associated with ART remained significant unless more than 56% of ART pts were cured by surgery alone. This threshold is greater than the estimated 12-yr FFBF of 46% after RP alone as determined by a contemporary nomogram. Conclusions: To the best of our knowledge, this represents the largest multi-institutional study to date comparing ART to ESRT. ART was associated with reduced biochemical recurrence, distant metastases, and death compared to ESRT for high-risk pts, pending prospective validation.

Fitting NTCP models to bladder doses and acute urinary symptoms during post-prostatectomy radiotherapy

BackgroundTo estimate the radiobiological parameters of three popular normal tissue complication probability (NTCP) models, which describe the dose-response relations of bladder regarding different acute urinary symptoms during post-prostatectomy radiotherapy (RT). To evaluate the goodness-of-fit and the correlation of those models with those symptoms.MethodsNinety-three consecutive patients treated from 2010 to 2015 with post-prostatectomy image-guided intensity modulated radiotherapy (IMRT) were included in this study. Patient-reported urinary symptoms were collected pre-RT and weekly during treatment using the validated Prostate Cancer Symptom Indices (PCSI). The assessed symptoms were flow, dysuria, urgency, incontinence, frequency and nocturia using a Likert scale of 1 to 4 or 5. For this analysis, an increase by ≥2 levels in a symptom at any time during treatment compared to baseline was considered clinically significant. The dose volume histograms of the bladder were calculated. The Lyman-Kutcher-Burman (LKB), Relative Seriality (RS) and Logit NTCP models were used to fit the clinical data. The fitting of the different models was assessed through the area under the receiver operating characteristic curve (AUC), Akaike information criterion (AIC) and Odds Ratio methods.ResultsFor the symptoms of urinary urgency, leakage, frequency and nocturia, the derived LKB model parameters were: 1) D50 = 64.2Gy, m = 0.50, n = 1.0; 2) D50 = 95.0Gy, m = 0.45, n = 0.50; 3) D50 = 83.1Gy, m = 0.56, n = 1.00; and 4) D50 = 85.4Gy, m = 0.60, n = 1.00, respectively. The AUC values for those symptoms were 0.66, 0.58, 0.64 and 0.64, respectively. The differences in AIC between the different models were less than 2 and ranged within 0.1 and 1.3.ConclusionsDifferent dose metrics were correlated with the symptoms of urgency, incontinence, frequency and nocturia. The symptoms of urinary flow and dysuria were poorly associated with dose. The values of the parameters of three NTCP models were determined for bladder regarding four acute urinary symptoms. All the models could fit the clinical data equally well. The NTCP predictions of urgency showed the best correlation with the patient reported outcomes.

Fitting NTCP models to bladder doses and acute urinary symptoms during post-prostatectomy radiotherapy

Fitting NTCP models to bladder doses and acute urinary symptoms during post-prostatectomy radiotherapy

Comparison Between Adjuvant and Early-Salvage Postprostatectomy Radiotherapy for Prostate Cancer With Adverse Pathological Features

Prostate cancer with adverse pathological features (ie, pT3 and/or positive margins) after prostatectomy may be managed with adjuvant radiotherapy (ART) or surveillance followed by early-salvage radiotherapy (ESRT) for biochemical recurrence. The optimal timing of postoperative radiotherapy is unclear. To compare the clinical outcomes of postoperative ART and ESRT administered to patients with prostate cancer with adverse pathological features. This multi-institutional, propensity score-matched cohort study involved 1566 consecutive patients who underwent postprostatectomy ART or ESRT at 10 US academic medical centers between January 1, 1987, and December 31, 2013. Propensity score 1-to-1 matching was used to account for covariates potentially associated with treatment selection. Data were collected from January 1 to September 30, 2016. Data analysis was conducted from October 1, 2016, to October 21, 2017. Freedom from postirradiation biochemical failure, freedom from distant metastases, and overall survival. All outcomes were measured from date of surgery to address lead-time bias. Of 1566 patients, 1195 with prostate-specific antigen levels of 0.1 to 0.5 ng/mL received ESRT and 371 patients with prostate-specific antigen levels lower than 0.1 ng/mL received ART. The median age (interquartile range) was 60 (55-65) years. After propensity score matching, the median (interquartile range) follow-up after surgery was similar between the ESRT and ART groups (73.3 [44.9-106.6] months vs 65.8 [40-107] months; P = .22). Adjuvant RT, compared with ESRT, was associated with higher freedom from biochemical failure (12-year actuarial rates: 69% [95% CI, 60%-76%] vs 43% [95% CI, 35%-51%]; effect size, 26%), freedom from distant metastases (95% [95% CI, 90%-97%] vs 85% [95% CI, 76%-90%]; effect size, 10%), and overall survival (91% [95% CI, 84%-95%] vs 79% [95% CI, 69%-86%]; effect size, 12%). Adjuvant RT, lower Gleason score and T stage, nodal irradiation, and postoperative androgen deprivation therapy were favorable prognostic features on multivariate analysis for biochemical failure. Sensitivity analysis demonstrated that the decreased risk of biochemical failure associated with ART remained significant unless more than 56% of patients in the ART group were cured by surgery alone. This threshold is greater than the estimated 12-year freedom from biochemical failure rate of 33% to 52% after radical prostatectomy alone, as determined by a contemporary dynamic nomogram. Adjuvant RT, compared with ESRT, was associated with reduced biochemical recurrence, distant metastases, and death for high-risk patients, pending prospective validation. These findings suggest that a greater proportion of patients with prostate cancer who have adverse pathological features may benefit from postprostatectomy ART rather than surveillance followed by ESRT.

Intermediate Endpoints After Postprostatectomy Radiotherapy: 5-Year Distant Metastasis to Predict Overall Survival

BackgroundIntermediate clinical endpoints (ICEs) prognostic for overall survival (OS) are needed for men receiving postprostatectomy radiation therapy (PORT) to improve clinical trial design. ObjectiveTo identify a potential ICE for men receiving PORT. Design, setting, and participantsWe performed an institutional review board–approved multi-institutional retrospective study of 566 men consecutively treated with PORT at tertiary care centers from 1986 to 2013. The median follow-up was 8.2 yr. Outcome measurements and statistical analysisBiochemical failure (BF), distant metastases (DM), and castrate-resistant prostate cancer (CRPC) were evaluated for correlation with OS and assessed as time-dependent variables in a multivariable Cox proportional hazards model and in landmark analyses at 1, 3, 5, and 7 yr after PORT. Cross-validated concordance (c) indices were used to assess model discrimination. Results and limitationsOS at 1, 3, 5, and 7 yr after PORT was 98%, 95%, 90%, and 82%, respectively. In a time-varying model controlling for clinical and pathologic variables, BF (hazard ratio [HR] 2.32, 95% confidence interval [CI] 1.45–3.71; p<0.001), DM (HR 6.52, 95% CI 4.20–10.1; p<0.001), and CRPC (HR 2.47, 95% CI 1.56–3.92; p<0.001) were associated with OS. In landmark analyses, 5-yr DM had the highest c index when adjusting for baseline covariates (0.78), with 5-yr DM also providing the greatest increase in discriminatory power over a model only including baseline covariates. These findings require validation in prospective randomized data. ConclusionsWhile limited by the retrospective nature of the data, 5-yr DM is associated with lower OS following PORT, outperforming the prognostic capability of BF and CRPC at 1, 3, 5, or 7 yr after treatment. Confirmation of this ICE as a surrogate for OS is needed from randomized trial data so that it can be incorporated into future clinical trial design. Patient summaryWe assessed potential intermediate clinical endpoints prognostic for overall survival in a cohort of men receiving radiotherapy after prostatectomy. We identified the development of metastatic disease within 5 yr after treatment as the strongest predictor of overall survival.

Post-Prostatectomy Radiotherapy in a Single Tertiary Institution: Outcomes Relating to Pre-Radiotherapy Prostate Specific Antigen

Objective: Timing of post-radical prostatectomy (RP) radiotherapy (RT) in patients with high risk prostate cancer continues to be debated. This is a retrospective review aiming to evaluate the influence of pre-RT prostate specific antigen (PSA) values on postprostatectomy RT outcomes in one Australian center. Method: Eligible patients were treated at the Royal Adelaide Hospital between January 2004 and December 2013, excluding those with nodal or distant metastatic disease pre-RT, or those who received neoadjuvant androgen deprivation therapy pre-RT. The primary endpoint of biochemical failure-free survival (bFFS) was defined as time from RP to date of biochemical failure (bF). Covariates of Gleason score, post-RP PSA, and pre-RT PSA were further analysed in relation to bFFS. Results: 103 of 122 patients underwent final analysis (8 were excluded for the above reasons; 11 had missing data). Median follow-up from RP was 60 months. Kaplan-Meier (KM) estimates of 1, 2, 3, 4 and 5-year survival probabilities were 93.5%, 83.4%, 82.4%, 76.6% and 71% respectively. There was no statistically significant correlation between bFFS and pathological T-stage (p=0.1), surgical margin involvement (p=0.7), or RT total dose (p=0.8). Analysis based on KM survival distributions and log-rank tests suggest that pathological Gleason score may have some influence on bFFS (p=0.04). Doubling the pre-RT PSA whilst holding all other factors and covariates constant, increases the hazard of bF at a particular time-point by approximately 19% on average. Conclusion: This single-institution retrospective study provides reasonable evidence for influence of pre-RT PSA on post-RP RT outcomes, arguing for earlier referral for RT.

Delineating sites of failure following post-prostatectomy radiation treatment using 68Ga-PSMA-PET

PurposeTo identify sites of failure with 68Ga-PSMA-PET (PSMA-PET) imaging in patients who have Biochemical Failure (BF) following post-prostatectomy radiotherapy. Material and methodsBetween June 2006 and January 2016, 409 men received post prostatectomy intensity modulated radiation treatment (IMRT) with protocolised planning. 310 patients received radiation treatment (RT) to the Prostate Fossa (PF) alone and 99 patients received RT to PF and pelvic lymphatics (PF + LN) usually in combination with androgen deprivation (AD) therapy. Any failure not detected on conventional imaging was delineated with PSMA-PET scanning. Sites of failure were characterised as in-field (PF ± LN), or out of field (nodal alone, distant metastatic alone (visceral or bone) or multi-site failure). Nodal failure was further divided into pelvic failure and/or distant failure. Results119 men developed BF, defined as a PSA rise of >0.2 or greater, above post-RT nadir. Freedom from BF was 71% in the PF group and 70% in the PF + LN group, with median follow up of 52 and 44 months respectively. AD was used concomitantly in 13% of the PF group and 92% of the PF + LN group. 81 patients with BF (68%) had PSMA-PET imaging performed as per study intent, 67 (80%) of whom had PSMA avid disease identified.PSMA-PET delineated in-field failure occurred in 2/50 (4%) of the PF group and 1/17 (6%) in the PF + LN group. Nodal failure alone was 33/50 (66%) for the PF group vs 7/17 (41%) for the PF + LN group. For the nodal only failure patients, 18/33 (55%) had pelvic-only nodal failure in the PF group compared to 1/7 (14%) in the PF + LN group (p = 0.03). 16 (32%) of the PSMA avid failures in the PF group would have been encompassed by standard pelvic lymphatic radiotherapy volumes. ConclusionPost-prostatectomy radiation treatment resulted in excellent in-field control rates. Isolated pelvic nodal failure was rare in those receiving radiotherapy to the prostatic fossa and pelvic nodes but accounted for one third of failures in those receiving PF alone treatment.

Variation in Radiotherapy Referral and Treatment for High-risk Pathological Features after Radical Prostatectomy: Results from a Population-based Study

AimsGuidelines recommend the discussion of adjuvant radiotherapy post-prostatectomy for prostate cancer patients with high-risk pathology to consider all of their treatment options. We determine whether patterns of radiotherapy referral and treatment post-prostatectomy reflect guideline-based use in a contemporary prostatectomy cohort. Materials and methodsElectronic treatment records were linked to Ontario's cancer registry. Multivariable regression was used to evaluate clinical and health systems factors associated with referral and the use of adjuvant radiotherapy within 6 months post-prostatectomy. ResultsAmong 2663 patients treated with prostatectomy between 1 January 2012 and 30 November 2012, 1261 (47%) were found to have adverse pathology and 492 were referred to radiation oncology ≤6 months post-prostatectomy, of whom 51% received adjuvant radiotherapy. Multivariable analysis showed that patients were more likely to be referred to radiation oncology from a low-volume surgical facility (≤50 versus >50 radical prostatectomy cases, odds ratio 2.50 [1.80–3.48]), if they lived farther from a radiotherapy centre (>50 km versus <10 km, odds ratio 1.73 [1.22–2.46]), if they were seen by radiation oncology preoperatively (odds ratio 1.95 [1.51–2.52]), or if they had adverse pathology: high T-category (pT3b/T4 versus pT2, odds ratio 17.87 [12.14–26.30]; pT3a versus pT2, odds ratio 5.24 [3.95–6.97]), positive margins (non-apex positive versus negative, odds ratio 4.20 [3.19–5.53]; apex only positive versus negative, odds ratio 2.60 [1.71–3.94]) and high Gleason score (8–10 versus ≤6, odds ratio 11.32 [5.37–23.84]; 7 versus ≤6, odds ratio 4.18 [2.16–8.10]). Wide geographic variation in radiotherapy referral rates persisted (range 6–66%; P < 0.0001). After radiotherapy referral, only high T-category (pT3b/T4 versus pT2, odds ratio 5.37 [3.01–9.60]; pT3a versus pT2, odds ratio 2.72 [1.59–4.65]) and non-apex positive margins (odds ratio 2.81 [1.86–4.23]) remained significantly predictive of treatment. ConclusionsVariations in referral for a discussion of radiotherapy post-prostatectomy are not mainly explained by patient characteristics. After seeing radiation oncology, treatment decisions correlated most strongly with pathological findings. Understanding the reasons for the tremendous non-clinical variations in care is needed to ensure access to potentially curative radiotherapy post-prostatectomy for high-risk prostate cancer patients.

Toxicity After Post Prostatectomy Image-Guided Intensity-Modulated Radiation Therapy Using Australian Guidelines

Australian post prostatectomy radiotherapy (PPRT) contouring and treatment guidelines are in use in clinical practice, but late toxicity outcomes have not been published and concern over toxicity may contribute to underutilization. In addition, there are no reports of late toxicity for patients treated with image-guidance using implanted fiducial markers. This study reports single institution toxicity outcomes after post prostatectomy radiotherapy (PPRT) via image guided intensity modulated radiation therapy (IG-IMRT) using the national eviQ guidelines. Baseline, acute and late toxicity data are reported both using incidence and prevalence which will help to inform radiation oncologists, patients and referring clinicians regarding the expected patterns of genitourinary, gastrointestinal and sexual toxicity before, during and after post prostatectomy radiotherapy. Prospectively collected toxicity data using Common Terminology Criteria for Adverse Events version 4 was reviewed for 293 men who underwent 64-66Gy IG-IMRT to the prostate bed between 2007 and 2015. Image-guidance was achieved via implanted fiducial markers. Median follow up after PPRT was 39 months. Baseline grade ≥ 2 genitourinary (GU), gastrointestinal (GI) and sexual toxicity was 20.5%, 2.7% and 43.7% respectively, reflecting ongoing toxicity after radical prostatectomy. Incidence of new (compared to baseline) acute grade ≥ 2 GU and GI toxicity was 5.8% and 10.6% respectively. New late grade ≥ 2 GU, GI and sexual toxicity occurred in 19.1%, 4.7% and 20.2% respectively, however many patients also experienced improvements in toxicities. For this reason, prevalence of grade ≥ 2 GU, GI and sexual toxicities four years after PPRT was similar to or lower than baseline (21.7%, 2.6% and 17.4% respectively). Baseline and acute grade ≥ 2 GU and sexual toxicity predicted respective late toxicities, while salvage intent predicted late grade ≥ 2 GU toxicity. There were no grade ≥ 4 toxicities. Post prostatectomy IG-IMRT using Australian contouring guidelines appears to have tolerable acute and late toxicity. The four year prevalence of grade ≥ 2 GU and GI toxicity was virtually unchanged compared to baseline, and sexual toxicity improved over baseline. This should reassure radiation oncologists following these guidelines. Late toxicity rates of surgery and PPRT are higher than following definitive IG-IMRT, and this should be taken into account if patients are considering surgery and likely to require PPRT.

Intermediate Endpoints After Postprostatectomy Radiation Therapy: 5-Year Distant Metastases to Predict Overall Survival

Intermediate Endpoints After Postprostatectomy Radiation Therapy: 5-Year Distant Metastases to Predict Overall Survival