Prostate-specific membrane antigen positron emission tomography detected local failure after post-prostatectomy radiation therapy: Low rates of out-of-field recurrence validates current Australian prostate bed contouring guidelines.

INTRODUCTION: The Australian Faculty of Radiation Oncology Genitourinary Group (FROGG) developed prostate bed clinical target volume (CTV) contouring guidelines which were subsequently used to develop the National EviQ guidelines for adjuvant and salvage post-prostatectomy radiotherapy (PPRT). These guidelines were based mainly upon consensus agreement. With the advent of prostate-specific membrane antigen (PSMA) positron emission tomography (PET), sites of recurrence can now be detected with low prostate-specific antigen (PSA) levels following radical prostatectomy. We evaluated sites of recurrence in patients treated with FROGG/EviQ CTVs to inform upcoming modifications of these guidelines. METHODS: At our institution, we use the FROGG/EviQ guidelines for PPRT. From 2015, patients with PSA failure following PPRT have been re-staged using PSMA PET imaging. We identified patients with PET-avid local, nodal, and distant recurrences, fusing them with original treatment plans to determine whether recurrences were within or outside the prostate bed CTV. Regional nodal failures were reviewed to determine if they were within current elective node contouring guidelines. RESULTS: Ninety-four patients had positive PSMA PET following PPRT. Nine (9.6%) recurrences were local, seven being local-only. One local recurrence (1.1%) was just superior to the contoured prostate bed CTV, located within the vas deferens. Seventy-three (77.7%) patients had a component of node failure, with 56 (59.6%) having node-only failure. Sites of nodal relapses were covered by standard contouring guidelines 60.3% of the time. CONCLUSION: The low recurrence rate outside of current prostate bed CTV contouring guidelines is consistent with other studies using contemporary contouring, and validates the efficacy of the current FROGG/EviQ prostate bed CTV definition.

Patterns of practice regarding use of radiation therapy following radical prostatectomy: A survey of Radiation Oncologists and Urologists in Australia and New Zealand.

INTRODUCTION: This study aimed to investigate the patterns of practices of radiation oncologists (ROs) and urologists in Australia and New Zealand with respect to the utilisation of post-prostatectomy radiation therapy (RT) and help guide the development of an update to the existing Faculty of Radiation Oncology Genito-Urinary Group post-prostatectomy guidelines. METHODS: ROs and urologists with subspecialty practice in prostate cancer from Australia and New Zealand were invited to participate in an online survey comprised of clinical scenarios regarding post-prostatectomy RT. RESULTS: Sixty-five ROs and 28 urologists responded to the survey. In the setting of low-risk biochemical relapse, the threshold for initiating RT was lower for ROs than urologists. ROs were more likely than urologists to recommend adjuvant RT for node-positive disease. When salvage RT was advised for a pT3N0R1 recurrence, there was no consensus amongst ROs on whether to add either ADT or nodal treatment over prostate bed RT alone. For a solitary PSMA-avid pelvic lymph node recurrence, whole pelvis RT with androgen deprivation therapy was the preferred treatment option (72% ROs, 43% urologists). Most ROs (92%) recommended conventionally fractionated RT to 66-70 Gy, with a boost to any PSMA PET avid recurrent disease. CONCLUSION: This survey highlights the marked discordance in practice for the management of prostate cancer relapse post-prostatectomy. This is seen not only between specialties but also within the radiation oncology community. This emphasises the need for an updated evidence-based guideline to be produced.

Outcomes of dose-escalated IMRT and ADT in Octogenarians with prostate cancer.

INTRODUCTION: We evaluated long-term outcomes for octogenarians with localised prostate cancer treated using dose-escalated image-guided intensity-modulated radiation therapy (IMRT) at our institution. METHODS: The charts of octogenarians treated for localised prostate cancer were retrospectively reviewed. Overall survival (OS), prostate cancer-specific survival (PCaSS), toxicity rates and changes from baseline were collected. RESULTS: The median follow-up was 97 months. Of 107 eligible patients, 27.1% had intermediate-risk and 72.9% had high-risk localised prostate cancer. Median dose was 78Gy, and 97.2% received ADT. OS was 91.4% and 67.2% at 5 and 10 years. PCaSS was 98.0% and 88.7% at 5 and 10 years. In all, 39 (36.4%) of patients died, with the cause of death known in 30: in 26.7% of these patients, prostate cancer was the cause of death. Grade ≥ 2 late GI and GU toxicity was 0.9% and 24.3% respectively. In all, 11.2% and 22.4% of patients reported worsening of GI or GU function from baseline, and 13.1% and 21.5% reported improvement in GI and GU function compared to baseline. CONCLUSION: Selected octogenarian patients with localised prostate cancer appear to benefit from radiation therapy and ADT. Despite excellent long-term PCaSS, 26.7% of patients died of prostate cancer. Rates of GI and GU toxicity were acceptable, and deterioration of urinary and bowel function compared to baseline was just as common as improvement in function from baseline.

PSMA-PET-guided dose-escalated volumetric arc therapy for newly diagnosed lymph node-positive prostate cancer: 5 Year outcomes following the FROGG and EviQ node-positive guidelines.

INTRODUCTION: The Royal Australian and New Zealand College of Radiologists (RANZCR) Faculty of Radiation Oncology Genitourinary Group (FROGG) guidelines and online EviQ protocols incorporate prostate-specific membrane antigen (PSMA) positron emission tomography (PET)-guided dose-escalated intensity-modulated radiation therapy (DE-IMRT) for newly diagnosed lymph node (LN) positive prostate cancer. We evaluated late toxicity and efficacy outcomes following the FROGG and EviQ approach. METHODS: Patients with LN-positive-only metastases on PSMA-PET imaging were offered curative therapy with 3 months neoadjuvant androgen deprivation therapy (ADT) followed by DE-IMRT and 3 years adjuvant ADT. IMRT was delivered via volumetric arc therapy (VMAT). We aimed to deliver 81 Gy in 45 fractions (Fx) to the prostate and PET-positive LNs, and 60 Gy in 45 Fx to elective pelvic nodes, contoured using the PIVOTAL guidelines. RESULTS: Forty-five patients were included. The median number of PET-positive nodes boosted was 2 (range 1-6) and median boost volume 1.16 cc (range 0.15-4.14). Seventeen (38%) patients had PET-positive nodes outside of PIVOTAL contouring guidelines. With 60 months median follow-up, disease-free, metastasis-free, prostate cancer-specific and overall survival were 88.1%, 95.3%, 100% and 91.5%. There were no in-field nodal failures. Late grade 1, 2 and 3 gastrointestinal toxicities occurred in 4%, 2% and 0% of patients, and genitourinary toxicity in 18%, 18% and 4%. Lower limb grade 2 lymphoedema occurred in three patients (7%). CONCLUSION: Outcomes following FROGG guidelines and EviQ are promising, with high long-term disease control and low toxicity. Contouring guidelines require modification due to the high rate of PET-positive nodes demonstrated beyond recommended coverage.

Single dose high-dose-rate brachytherapy with focal dose escalation for prostate cancer: Mature results of a phase 2 clinical trial.

AIM: The dominant intraprostatic lesion (DIL) is the commonest site of relapse after single dose high-dose-rate brachytherapy (HDR-BT) for localised prostate cancer. This study investigated toxicity and clinical outcomes of focal dose escalation to the DIL with dose de-escalation to the remaining prostate. MATERIALS/METHODS: Between November 2012 and July 2016, 50 patients with localised prostate adenocarcinoma received single fraction HDR-BT. 21 Gy was prescribed to the DIL, with two de-escalation prescription schedules for the remaining prostate. Primary outcomes included biochemical no evidence of disease (bNED), local recurrence free survival (LRFS), and metastasis free survival (MFS). Secondary outcomes included late genitourinary, gastrointestinal and sexual toxicity. Kaplan-Meier analyses with log rank tests were used to estimate bNED, LRFS and MFS. RESULTS: With a median follow up of 70.6 months, 15 patients developed biochemical failure, including 8 in the group that received minor dose de-escalation to the non-DIL prostate (group 1) and 7 in the group that received moderate de-escalation (group 2). Five-year bNED was 88% in group 1 and 76% in group 2 (p = 0.05). Overall 4-year and 5-year FFLF in group 1 was 100% and 96% and in group 2 92% and 84%. These differences were statistically significant (p = 0.03). No acute ≥G3 genitourinary or ≥G2 gastrointestinal toxicity was reported. The median IIEF decreased in the first 6 months improving to a peak median score of 20 at 54 months. CONCLUSION: Focal boost to the DIL did not improve biochemical or local control after single-fraction HDR monotherapy compared to what would be expected from 19 Gy single fraction treatment to the whole gland.

Ultra-hypofractionated radiotherapy for low- and intermediate risk prostate cancer: High-dose-rate brachytherapy vs stereotactic ablative radiotherapy.

PURPOSE: To compare the biochemical control rates (BCRs), late gastrointestinal (GI) and genitourinary (GU) toxicities in patients with low- and intermediate risk prostate cancer (PCa) treated with high-dose-rate brachytherapy (HDR BT) of 19 Gy/1 fraction, 26 Gy/2 fractions, or stereotactic ablative radiotherapy (SABR) of 36.25 Gy/5 fractions. METHODS AND MATERIALS: Between August 2008 and December 2017, patients with low- and intermediate risk PCa who received single dose or 2-fraction HDR BT, or 5-fraction SABR at a single institution were included. BCR for the whole population and the individual treatment groups were calculated using the Phoenix definition. Post treatment GI and GU toxicities were evaluated according to the CTCAE v4.0 guidelines. RESULTS: 185 patients with low- and intermediate risk PCa were included in this study with a median follow up of 60.5 months. BCRs at 3 and 5 years were 95% and 85% for all patients. The 5-year BCRs were 69%, 95% and 92% for the 19 Gy/1 fraction, 26 Gy/2 fractions and 36.25 Gy/5 fractions groups respectively. The cumulative 5-year incidence rates of ≥grade 2 GI events in the 19 Gy/1fr, 26 Gy/2fr and 36.25 Gy/5fr groups were 0%, 2% and 4%, respectively. Incidence rates in those treated in the 5-fraction SABR arm were significantly higher (p < 0.05) than those treated in both HDR BT arms where no statistically significant difference between the two HDR BT groups was seen (p = 0.15). The cumulative 5-year incidence rates of ≥grade 2 GU events in the 19 Gy/1fr, 26 Gy/2fr and 36.25 Gy/5fr groups were 30%, 5% and 6%, respectively. No statistically significant difference was found between the 26 Gy/2fr and 36.25 Gy/5fr (p = 0.37) treatment arms but the incidence rate in the 26 Gy/2fr were significantly lower than those seen after 19 Gy/1fr (p < 0.05). CONCLUSIONS: 26 Gy/2 fractions HDR BT provided equivalent BCR with lower toxicity compared to 36.25 Gy/5 fractions SABR. Both 2-fraction HBR BT and 5-fraction SABR achieved better BCRs than single dose 19 Gy HDR BT. The two-fraction HDR BT schedule should be considered as an important comparator in future clinical trials.

Dosimetry of local failure with single dose 19 Gy high-dose-rate brachytherapy for prostate cancer.

PURPOSE/OBJECTIVE: Long-term follow up of single dose high-dose rate brachytherapy (HDR BT) for localised prostate cancer has revealed higher than expected rates of biochemical and local failure. This study aimed (i) to investigate the pattern of relapse within the prostate with reference to the initial site of disease in those patients; and (ii) to examine if there were any relationships between the HDR BT dosimetric parameters to these areas of recurrence. MATERIALS/METHODS: A retrospective review of treatment records of patients who received 19 Gy single fraction of HDR BT was carried out. A matched pair analysis used one control for each biochemical recurrence case matched with pre-treatment Clinical target volume (CTV) size, Gleason score, T stage, risk category and presence of an identifiable dominant intraprostatic nodule (DIL) for each biochemical recurrence case identified. For all datasets, the pre HDR BT DILs were delineated on the diagnostic pre-treatment T2-weighted MRI and planning CT images. For patients with local recurrence post HDR BT, the recurrent nodules were contoured on the diagnostic T2-weighted MRI and choline PET which were registered to the original HDR BT planning CT. Dosimetric parameters of CTV, planning target volume (PTV), DIL and organs at risk (OARs) were evaluated. Wilcoxon signed-rank test was performed to investigate if there were any significant differences in dosimetric parameters between cases and controls. Cox regression analysis was performed to explore if there were any clinical and dosimetric parameters predicting for biochemical progression free survival (bPFS), local recurrence free survival (LR-PFS) and DIL recurrence free survival (DIL-PFS). RESULTS: Between 2013 and 2018, 180 patients received 19 Gy HDR-BT monotherapy. With a median follow up of 36 months, 19 (10.6%) patients developed biochemical recurrence. Of the 19 patients with biochemical failure, 13 had a local recurrence, including 7 who occurred at the site of DIL. Thirty-eight intermediate/high risk patients were included in the matched pair analysis. No statistically significant differences were found in all CTV, PTV, DIL and OAR dosimetric parameters between cases and controls (p > 0.05). For the Cox regression analysis, none of the covariates investigated were found to be statistically significant factors to predict for bPFS, LC-PFS and DIL-PFS. CONCLUSION: No associations between biochemical recurrences and HDR BT dosimetry were identified in our cohort of patients receiving 19 Gy single fraction HDR BT. A large proportion of recurrences occurred at the site of original disease. HDR BT for intermediate/high risk prostate cancer should be undertaken using a minimum of two fractions.