Intermediate clinical endpoints for surrogacy in localised prostate cancer: an aggregate meta-analysis

Gharzai, L.A.; Jiang, Ralph; Wallington, David G.; Jones, Gavin; Birer, Samuel R.; Jairath, Neil; Jaworski, E; McFarlane, Matthew; Mahal, Brandon A.; Nguyen, Paul L.; Sandler, Howard M.; Morgan, Todd M.; Reichert, Zachery R.; Alumkal, Joshi J.; Mehra, Rohit; Kishan, Amar U.; Fizazi, Karim; Halabi, Susan; Schaeffer, Edward M.; Feng, Felix Y.; Elliott, David; Dess, Robert T.; Jackson, W. Clay; Schipper, Matthew J.; Spratt, Daniel E.

doi:10.1016/s1470-2045(20)30730-0

Cited by 89 publications

(60 citation statements)

References 17 publications

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“…After aRT, patients no longer have this option. Unlike distant metastasis-free survival (DMFS) as a validated surrogate endpoint [25] , bPFS has not been shown to be a surrogate for harder endpoints such as overall survival (OS).…”

Section: Discussionmentioning

confidence: 99%

Time management: Improving the timing of post-prostatectomy radiotherapy, clinical trials, and knowledge translation

Ooi

Pereira

Nagar

et al. 2021

Clinical and Translational Radiation Oncology

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Background Management of prostate cancer after surgery is controversial. Past studies on adjuvant radiotherapy (aRT) for higher-risk features have had conflicting results. Through the collaborative conversations of the global radiation oncology Twitter-based journal club (#RadOnc #JC), we explored this complex topic to share recent advances, better understand what the global radiation oncology community felt was important and inspire next steps. Methods We selected the recent publication of a landmark international randomized controlled trial (RCT) comparing immediate and salvage radiotherapy for prostate cancer, RADICALS-RT, for discussion over the weekend of January 16 to 17, 2021. Coordination included open access to the article and an asynchronous portion to decrease barriers to participation, cooperation of study authors (CP, MS) who participated to share deeper insights including a live hour, and curation of related resources and tweet content through a blog post and Wakelet journal club summary. Discussion of Results Our conversations created 2,370,104 impressions over 599 tweets with 51 participants spanning 11 countries and 5 continents. A quarter of the participants were from the US (13/51) followed by 10% from the UK (5/51). Clinical or Radiation Oncologists comprised 59% of active participants (16/27) with 62% (18/29) reporting giving aRT within the last 5 years. Discussion was interdisciplinary with three urologists (11%), three trainees (11%), and two physiotherapists (7%). Four months after the journal club its article Altmetric score had increased by 7% (214 to 229). Thematic analysis of tweet content suggested participants wanted clarification on definitions of adjuvant (aRT) and salvage radiotherapy (sRT) including indications, timing, and decision-making tools including guidelines; more interdisciplinary and cross-sectoral collaboration including with patients for study design including survivorship and meaningful outcomes; more effective knowledge translation including faster clinical trials; and more data including mature results of current trials, particular high-risk features (Gleason Group 4+, pT4b+, and margin-positive disease), implications of newer technologies such as PSMA-PET and genomic classifiers, and better explanations for practice pattern variations including underutilization of radiotherapy. This was further explored in the context of relevant literature. Conclusion Together, this global collaborative review on the postoperative management of prostate cancer suggested a stronger signal for the uptake of early salvage radiation treatment with careful PSA monitoring, more sensitive PSA triggers, and expected access to radiotherapy. Questions still remain on potential exceptions and barriers to use. These require better decision-making tools for all practice settings, consideration of newer technologies, more pragmatic trials, and better use of social media for knowledge transl...

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Section: Discussionmentioning

confidence: 99%

Time management: Improving the timing of post-prostatectomy radiotherapy, clinical trials, and knowledge translation

Ooi

Pereira

Nagar

et al. 2021

Clinical and Translational Radiation Oncology

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“…The use of surrogate endpoints should be limited to those for which evidence exists of their validity (e.g. metastasis-free survival in localised prostate cancer [ 128 ]). Head-to-head comparisons of new drugs and use of the standard of care in control arms should be the norm instead of comparing many new ‘same class’ drugs to inappropriate control arms.…”

Section: Raising the Barmentioning

confidence: 99%

An urgent call to raise the bar in oncology

et al. 2021

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Important breakthroughs in medical treatments have improved outcomes for patients suffering from several types of cancer. However, many oncological treatments approved by regulatory agencies are of low value and do not contribute significantly to cancer mortality reduction, but lead to unrealistic patient expectations and push even affluent societies to unsustainable health care costs. Several factors that contribute to approvals of low-value oncology treatments are addressed, including issues with clinical trials, bias in reporting, regulatory agency shortcomings and drug pricing. With the COVID-19 pandemic enforcing the elimination of low-value interventions in all fields of medicine, efforts should urgently be made by all involved in cancer care to select only high-value and sustainable interventions. Transformation of medical education, improvement in clinical trial design, quality, conduct and reporting, strict adherence to scientific norms by regulatory agencies and use of value-based scales can all contribute to raising the bar for oncology drug approvals and influence drug pricing and availability.

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“…The International Intermediate Clinical Endpoints in Cancer of the Prostate working group assessed the performance of commonly used intermediate clinical endpoints across all randomized controlled trials (RCTs) in localized PCa. [ 6 ] They looked at 75 RCTs (53,631 patients) on localized or biochemically recurrent PCa between 1970 and 2020 with at least 70 participants. Only MFS correlated strongly and PFS showed modest correlation with OS.…”

Section: Intermediate Markers Of Survival In Pca-how Valid?mentioning

confidence: 99%

Round Up

Kumar

2021

Indian J Urol

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Intermediate clinical endpoints for surrogacy in localised prostate cancer: an aggregate meta-analysis

Cited by 89 publications

References 17 publications

Time management: Improving the timing of post-prostatectomy radiotherapy, clinical trials, and knowledge translation

Time management: Improving the timing of post-prostatectomy radiotherapy, clinical trials, and knowledge translation

An urgent call to raise the bar in oncology

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