Clinicians may now have a better idea of how best to treat men with intermediate- and high-risk and locally advanced prostate cancer.
The 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed an international panel of experts for their opinions about key dilemmas in clinical management to help supplement evidence-based guidelines. The questionnaires were specifically designed to help better guide clinicians and their patients in decision-making when there is little or no high level evidence to guide treatment decisions.
Significant advances in imaging and molecular characterization have created a shift in treatment practices. Coupled with a host of new therapies, these advancements are significantly improving outcomes in advanced prostate cancer. However, there is a lack of high-level evidence on a variety of clinical topics that greatly impact daily practice. The APCCC set up a forum to discuss and debate current diagnostic and treatment options for men with advanced prostate cancer.
“There are still a lot of questions in areas where strong evidence is missing,” said first author Silke Gillessen, MD, Primario, Direttore Medico e Scientifico, Istituto Oncologico della Svizzera Italiana (IOSI), Ospedale San Giovanni, Faculty of Biomedical Sciences, USI, Lugano, Switzerland. “Specifically in areas that are very important for patients, but less for pharmaceutical companies, such as de-escalation of treatment or treatment of side effects like hot flashes.”
Early Salvage RT Favored
Before the conference, a panel of 117 international prostate cancer experts were asked to answer multiple choice consensus questions on intermediate-risk, high-risk, and locally advanced prostate cancer. The questions included treatment choices for biochemical recurrence after local treatment and treatment choices for side effects from hormonal therapies. Consensus was defined as 75% agreement or more and strong consensus as 90% agreement or more. Survey findings were reported in European Urology.
“We found consensus for using PSMA-PET [prostate-specific membrane antigen-positron emission tomography] for staging patients with high-risk localized disease,” Dr Gillessen said. “There was also consensus to offer elective radiotherapy to the pelvic nodes. Interestingly, a lot of panelists voted for early salvage radiotherapy, not adjuvant [therapy], in patients with a high risk of relapse.”
Survey findings showed that PSMA-PET has become the preferred imaging modality for men with biochemical relapse. Scientific evidence on its optimal use in various patient settings is lacking, however.
For systemic staging of clinically localized prostate cancer, in addition to prostate MRI, 78% of panelists voted to recommend upfront PSMA-PET with or without subsequent conventional imaging, according to the report’s authors. For patients with clinically localized prostate cancer with PSMA-positive findings consistent with bone metastases on the CT component of upfront PSMA-PET, 78% of panelists voted not to recommend additional imaging such as MRI or bone scintigraphy. For patients with clinically localized high-risk prostate cancer, 77% of panelists voted to recommend use of PSMA-PET.
The survey revealed no consensus as to whether to give systemic therapy along with salvage radiotherapy or for how long even though this is a relatively common clinical setting, Dr Gillessen said. “In terms of hormonal treatments, we found that there is consensus to check for drug-drug interactions when starting an ARPI [androgen receptor pathway inhibitor],” she said. “Interestingly, only a minority of panelists voted for an ECG or more intensive cardiac evaluation before starting treatment with hormonal treatment for the majority of patients.”
The panelists were queried on their recommendations for treatment of metastatic hormone-sensitive prostate cancer, nonmetastatic castration-resistant prostate cancer, metastatic castration-resistant prostate cancer, and oligometastatic and oligoprogressive prostate cancer. All of the questions were administered via a web-based survey to 105 physician panelists directly engaged in prostate cancer treatment decision-making.
Voting results revealed varying degrees of consensus, and the discussions did not incorporate any formal literature reviews or meta-analyses. It is hoped that these findings can help policymakers and other stakeholders better decide how best to prioritize areas of future research. The authors wrote that “although this report captures what experts in the field think today, it should be interpreted and integrated into clinical practice with the same scrutiny that any other major paper would receive, and with the knowledge that consensus does not constitute or substitute for evidence.”
Expert opinion statements have limitations, but APCCC has worked to address some of those by significantly expanding the number of voting panel members from 61 experts in 2019 to 105 experts in 2022. Of these, 50% were medical oncologists, 29% urologists, and 21% clinical oncologists and radiation oncologists.
The consensus conference is only for controversial areas in which high level evidence is scant. “We specifically go for these topics with our questions,” Dr Gillessen said. “Therefore clinicians who have less experience with prostate cancer because they treat a wide variety of different tumors, can check in the report what world experts are doing in specific situations where there is no strong evidence. We hope that therefore their patients will profit from the transfer of ‘concentrated knowledge’ of experts to their treating physician.”
PSA persistence is defined in most studies as detectable PSA of 0.1 ng/mL or greater within 4 to 8 weeks after radical prostatectomy. In men with PSA persistence, the benefit of salvage RT with or without ADT remains unclear because there are no trials that have specifically investigated this issue.
Nirmish Singla, MD, MSc, Director of Translational Research in Genitourinary Oncology and an associate professor of urology and oncology at Johns Hopkins University in Baltimore, Maryland, said there has been a recent emergence of several new agents and treatment approaches for men with advanced prostate cancer in a variety of settings. The challenge for clinicians, however, is deciding on the optimal strategy at the individual patient level.
“I believe that expert panels are beneficial to brainstorm and synthesize the evidence and help identify knowledge gaps,” Dr Singla said. “It is important to have a well-balanced, multidisciplinary panel given the role for multimodal approaches in managing advanced prostate cancer.” Further, he noted that a panel made up of experts in urology, medical oncology, and radiation oncology is critical to ensure a balanced discussion and mitigate bias.
“As a clinician, I found the paper useful as the survey questions represent scenarios that patients and physicians face every day,” said Saum Ghodoussipour, MD, a urologic oncologist who is an assistant professor of surgery at Rutgers Robert Wood Johnson Medical School and Director of the Bladder and Urothelial Cancer Program at Rutgers Cancer Institute of New Jersey in New Brunswick. “The varied consensus reflects limitations in the existing literature and most importantly, the new gaps in understanding that we are fortunate to face with the development of advanced imaging modalities and novel androgen receptor pathway inhibitors and antagonists.”
While the findings of this panel do not fill any knowledge gaps or provide “guideline level” evidence, they suggest that most of the questions raised can be better addressed through PSMA-PET, novel drugs, genomic classifiers, and patient reported outcomes in ongoing trials. Dr Ghodoussipour said the needle is likely to continue to move in prostate cancer care and new questions will arise. “Expert consensus statements like this will always be welcomed so that we can push to provide the best treatments and outcomes for our patients,” Dr Ghodoussipour said.
Gillessen S, Bossi A, Davis, ID et al. Management of patients with advanced prostate cancer. Part I: Intermediate-/high-risk and locally advanced disease, biochemical relapse, and side effects of hormonal treatment: Report of the Advanced Prostate Cancer Consensus Conference 2022. Eur Urol. Published online December 6, 2022. doi:10.1016/j.eururo.2022.11.002