The use of combination RT and androgen deprivation therapy in many prostate cancer curative-intent treatment scenarios is supported by level 1 evidence. However, in our current clinical paradigm, we ...have no ability to determine a priori which patients truly benefit from combination therapy and therefore apply the combination RT and androgen deprivation therapy intensification strategy to all patients, which results in overtreatment or undertreatment of the majority of our patients. Genomics has the ability to more deeply and objectively characterize the disease, in turn refining our prognostication capabilities and enabling the individualization of treatments. We review the commercially available prostate cancer genomic tests, focusing on those able to predict patient outcomes following radiotherapy or guide radiotherapy treatment decisions.
The hypothesis of a curable oligometastatic prostate cancer (PCa) state remains to be clinically-proven. Conventional imaging often fails to localize early recurrences, hampering the potential for ...radical approaches.
We hypothesize that prostate-specific membrane antigen (PSMA)-targeted PET-MR/CT allows for earlier detection and localization of oligorecurrent-PCa, unveiling a molecularly-defined state amenable to curative-intent metastasis-directed treatment (MDT).
Single-institution single-arm phase-two study. Patients with rising PSA (0.4-3.0 ng/mL) after maximal local therapy (radical prostatectomy and post-operative radiotherapy), negative conventional staging, and no prior salvage hormonal therapy (HT) were eligible.
All patients underwent 18FDCFPyL PET-MR/CT. Patients with molecularly-defined oligorecurrent-PCa had MDT (stereotactic ablative body radiotherapy SABR or surgery) without HT.
Primary endpoint was biochemical response (complete, i.e. biochemical ‘no evidence of disease’ bNED, or partial response 100% or ≥50% PSA decline from baseline, respectively) after MDT. Simon’s two-stage design was employed (null and alternate hypotheses <5% and >20% response rate, respectively), with α and β of 0.1.
Seventy-two patients were enrolled (May/2017-July/2019). Thirty-eight (53%) had PSMA-detected oligorecurrent-PCa amenable for MDT. Thirty-seven (51%) agreed to MDT: 10 and 27 underwent surgery and SABR, respectively. Median follow-up was 15.9 months (IQR 9.8-19.1). Of patients receiving MDT, the overall response rate was 60%, including 22% rendered bNED. One (2.7%) grade 3 toxicity (intra-operative ureteric injury) was observed.
PSMA-defined oligorecurrent-PCa can be rendered bNED, a necessary step towards cure, in 1 of 5 patients receiving MDT alone. Randomized trials are justified to determine if MDT +/− systemic agents can expand the curative therapeutic armamentarium for PCa.
We studied men treated for prostate cancer with rising PSA. We found PSMA imaging detected recurrent cancer in three-quarters of patients, and targeted treatment to these areas significantly decreased PSA in half of patients.
The aim of this work is to report on the results of a phase 2 randomized trial of moderately hypofractionated (MH) versus conventionally fractionated (CF) radiation therapy to the prostate with ...elective nodal irradiation.
This was a single-center, prospective, phase 2 randomized study. Patients with high-risk disease (cT3, prostate-specific antigen level >20 ng/mL, or Gleason score 8-10) were eligible. Patients were randomized to either MH using a simultaneous integrated boost (68 Gy in 25 fractions to prostate; 48 Gy to pelvis) or CF (46 Gy in 23 fractions with a sequential boost to the prostate of 32 Gy in 16 fractions), with long-term androgen deprivation therapy. The primary endpoint was grade ≥2 acute gastrointestinal (GI) and genitourinary (GU) toxicity (Common Terminology Criteria for Adverse Events version 3.0). Secondary endpoints included late GI and GU toxicity, quality of life, and oncologic outcomes.
One-hundred eighty patients were enrolled; 90 were randomized to and received MH and 90 to CF. The median follow-up was 67.4 months. Seventy-five patients (41.7%) experienced a grade ≥2 acute GI and/or GU toxicity, including 34 (37.8%) in the MH and 41 (45.6%) in the CF arms, respectively (P = .29). Late grade ≥2 GI (P = .07) and GU (P = .25) toxicity was not significantly different between arms; however, late grade ≥3 GI toxicity was worse in the MH group (P = .01). There were no statistically significant quality-of-life differences between the 2 treatments. There were no statistically significant differences observed in cumulative incidence of biochemical failure (P = .71) or distant metastasis (P = .31) and overall survival (P = .46).
MH to the prostate and pelvis with androgen deprivation therapy for men with high-risk localized prostate cancer was not significantly different than CF with regard to acute toxicity, quality of life, and oncologic efficacy. However, late grade ≥3 GI toxicity was more common in the MH arm.
•Long-term results of elective nodal irradiation and hypofractionated prostate boost.•At 10 years, biochemical failure 33%, distant metastasis 17% and survival 76%•Low cumulative incidence of grade ...≥3 gastrointestinal and genitourinary toxicity.
To report on long-term results of elective pelvic nodal irradiation (EPNI) and a simultaneous hypofractionated prostate boost for high-risk prostate cancer.
This was a prospective single-arm study. Patients with high-risk disease (cT3, PSA >20 ng/mL, or Gleason score 8–10) were eligible. Patients received 45 Gy in 25 fractions to the prostate and pelvic lymph nodes with a simultaneous intensity-modulated radiotherapy boost of 22.5 Gy to the prostate (total dose 67.5 Gy in 25 fractions), with androgen deprivation therapy (ADT) for 2–3 years. The primary endpoint was biochemical failure. Secondary endpoints included distant metastases and overall survival. Multivariable analysis was performed to look for predictive factors. Late toxicity was assessed using CTCAE v3.0.
230 patients enrolled. Median follow-up was 11.2 years (IQR 8.1–12.9). At 10 years, cumulative incidence of biochemical failure was 33.4%, distant metastasis was 16.5%, and overall survival was 76.3%. On multivariable analysis, PSA nadir ≥0.05 ng/mL was associated with biochemical failure (HR 6.8, 95% CI 4–11.8, p < 0.001) and distant metastases (HR 7.5, 95% CI 3.9–14.5, p < 0.0001). PSA nadir ≥0.1 ng/mL (HR 5.2, 95% 2.2–12, p = 0.0001) and ADT use ≤12 months (versus >24 months) (HR 2.3, 95% CI 1.3–3.9, p = 0.004) were associated with worse survival. The 5-year cumulative incidence of any late grade ≥3 gastrointestinal and genitourinary toxicity was 2.3% and 7.5%, respectively.
EPNI and a simultaneous hypofractionated prostate boost combined with long-term ADT for high-risk prostate cancer resulted in acceptable 10-year biochemical control and survival with low grade ≥3 toxicity.
Radiotherapy (RT) is a standard-of-care option for localized prostate cancer (PCa), with oncological outcomes similar to those for surgery. Late toxicities of modern RT for PCa are uncommon thanks to ...technical advances that have translated to continuous improvements in the therapeutic index of prostate RT.
Radiotherapy is a mainstay treatment option for localized prostate cancer (PCa), with oncological outcomes similar to those with surgery. Standard-of-care radiotherapy approaches include brachytherapy, hypofractionated external beam radiotherapy (EBRT), and EBRT with brachytherapy boost. Given the long survival associated with PCa and these curative-intent radiotherapy approaches, late toxicity is a paramount consideration. In this narrative mini-review, we summarize late toxicities associated with standard-of-care radiotherapy approaches including stereotactic body radiotherapy, an advanced radiotherapy technique supported by accumulating evidence. We also discuss stereotactic magnetic resonance imaging–guided adaptive radiotherapy (SMART), an emerging paradigm that may further improve the therapeutic index of radiotherapy and reduce late toxicities.
This mini-review summarizes late side effects associated with standard and advanced radiotherapy techniques for localized prostate cancer. We also discuss a new radiotherapy approach called SMART that may reduce late side effects and increase treatment effectiveness.
•Ultra-hypofractionated elective nodal RT was studied in 4 prospective trials.•The incidence of grade 3+ acute or late GI or GU toxicity was low.•Bowel and sexual quality of life worsened for 1 year ...post treatment.•Oncologic outcomes were very favorable, however longer follow-up is needed.•This is the largest prospective series of ultra-hypofractionated elective nodal RT.
The role of elective nodal irradiation (ENI) in localized prostate cancer (PCa) is controversial. With increasing use of SBRT to the prostate, data is needed regarding the safety and efficacy of ENI using ultra-hypofractionated radiation (UHRT).
Between 2013–2020, 4 prospective clinical trials of intermediate or high-risk PCa receiving dose-escalated RT to the prostate (via HDR brachytherapy or SBRT boost) and ENI using UHRT (25 Gy in 5 weekly fractions) were conducted. Primary endpoints included acute genitourinary and gastrointestinal toxicities (CTCAE v3.0/4.0), and secondary endpoints included late genitourinary and gastrointestinal toxicities, patient-reported quality of life (EPIC) and biochemical failure (Phoenix definition).
One-hundred sixty-five patients were enrolled, of whom 98 (59%) had high-risk disease. ADT was used in 141 (85%). Median follow-up was 38 months (IQR 10–63). The worst acute genitourinary and gastrointestinal toxicities respectively were 48% and 7.5% for grade 2, and 2.7% and 0% for grade 3. Cumulative incidence of late grade 2+ genitourinary and gastrointestinal toxicities at 36 months were 58% and 11.3% and for late grade 3+ toxicities were 1% and 0%, respectively. No grade 4+ acute or late toxicities were observed. Bowel and sexual toxicity significantly worsened up to 1-year compared to baseline. Over time, urinary (p < 0.0001), bowel (p = 0.0018) and sexual (p < 0.0001) scores significantly improved. The 3-year biochemical recurrence-free survival was 98%.
ENI using UHRT is associated with low incidence of grade 3+ toxicity, while grade 1–2 acute genitourinary and gastrointestinal toxicity is common. Randomized phase 3 trials are needed.
We conducted and previously published a phase 2 trial of metastasis-directed therapy (MDT) in men with recurrence of prostate cancer at a low prostate-specific antigen level following radical ...prostatectomy and postoperative radiotherapy. All patients had negative conventional imaging and underwent prostate-specific membrane antigen (PSMA) positron emission tomography (PET). Patients without visible disease (n = 16) or with metastatic disease not amenable to MDT (n = 19) were excluded from the interventional study. The remaining patients with disease visible on PSMA-PET received MDT (n = 37). We analyzed all three groups to identify distinct phenotypes in the era of molecular imaging–based characterization of recurrent disease. Median follow up was 37 mo (interquartile range 27.5–43.0). There was no significant difference in time to the development of metastasis on conventional imaging among the groups; however, castrate-resistant prostate cancer-free survival was significantly shorter for patients with PSMA-avid disease not amenable to MDT (p = 0.047). Our findings suggest that PSMA-PET findings can help in discriminating diverging clinical phenotypes among men with disease recurrence and negative conventional imaging after local therapies with curative intent. There is a pressing need for better characterization of this rapidly growing population of patients with recurrent disease defined by PSMA-PET to derive robust selection criteria and outcome definitions for ongoing and future studies.
In men with prostate cancer with rising PSA levels following surgery and radiation, a newer type of scan called PSMA-PET (prostate-specific membrane antigen positron emission tomography) can be used to characterize and differentiate the patterns of recurrence, and inform future cancer outcomes.
Collaborative partnerships, which link two health organizations with shared characteristics to achieve common goals and to improve healthcare quality, are becoming increasingly common in oncology. ...The purpose of this study is to review the collaboration between King Hussein Cancer Center (KHCC) and Princess Margaret Cancer Centre (PM). The context, input, process, and product (CIPP) model, a quasi-experimental form of program evaluation, has been applied to the KHCC-PM collaboration. This model is well suited to evaluate complex collaborations as it does not assume linear relationships. Data sources include stakeholders’ judgements of the collaboration, assessment of achievements, and informal interviews with key participants involved in the program. KHCC and PM are recognized as high-caliber comprehensive cancer centers, with a common goal of delivering high-quality care to patients. Through personal relationships among faculty in the centers and the perceived opportunities for mutual benefit, KHCC and PM signed a memorandum of understanding in 2013 to enter into a formal partnership. This partnership has been an evolving process that started with collaboration on education and grew to include clinical care. Research is an area for potential future collaboration. Enabling factors in the collaboration include dedication of individuals involved, trusting relationships amongst faculty, and the reciprocal nature of the relationship. Challenges have been financial, competing interests, and the absence of a successful collaborative model to follow. The KHCC and PM collaboration has been successful. A strategic plan is being developed and followed to guide areas of expansion.
