Alibrex: A New Blood Test to Reveal Whether a Cancer Treatment is Working

Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

Kevin Knopf, MD
Chief Medical Officer, Cadex Genomics; CMO and Division Chief of Hematology/Oncology, Highland Hospital (Oakland)

In cancer treatment, time is of the essence. Our Curious Dr. George asks Kevin B. Knopf, MD, MPH, Chief Medical Officer at Cadex Genomics, how his company’s new test, Alibrex, could rapidly reveal how well a given treatment is working for a given patient.

Curious Dr. George: The U.S. Food and Drug Administration has approved about 270 anti-cancer drugs. The National Comprehensive Cancer Network publishes guidelines for treatment of about 61 major cancer types. Although there is consensus on first- and second-line therapy, there may be a substantial delay before a patient’s oncologist can determine whether the therapy chosen is working for them. Your company Cadex Genomics has a new test to evaluate whether an agent is active against a tumor in a given patient. You claim that your test, Alibrex, is agnostic to tumor type, tissue of origin, and the name of the drug and can give an answer quickly. Can you describe the test, how it works, and how it is performing at this early time?

Kevin B. Knopf, MD, MPH: Alibrex is being developed to identify stage IV cancer patients who are not responding to treatment, allowing for an early switch to more effective therapy. Specifically, the test identifies patients whose tumor is rapidly growing during treatment. Alibrex requires a blood draw prior to therapy being administered, and another prior to the next cycle of treatment. Using quantitative polymerase chain reaction qPCR technology, cell-free DNA (cfDNA) concentration levels are measured in each blood draw to determine if the tumor is growing.

The concept is straightforward: as tumors grow, the amount of cfDNA the tumor sheds into the blood increases. Alibrex takes advantage of this by picking up the increase in cfDNA and determining whether the patient has disease progression. The advantage of evaluating cfDNA versus circulating tumor DNA (ctDNA) is that all tumors shed cfDNA with increasing amounts as the tumor grows. Compared to cfDNA, ctDNA is a far more complex approach in that different tumors shed different types of ctDNA.

A concern with this approach is that increases in cfDNA may be seen from other non-cancer-related sources, such as infections, white blood cell lysis, injury, or a number of other events unrelated to tumor growth. It is possible for a patient with such an event, prior to a blood draw, to have a result that is a false positive or negative due to the impact of changing levels of non-cancer cfDNA.

To overcome this problem, Alibrex assesses short cfDNA fragment lengths; it has been published and recognized that short cfDNA fragments are specific to cancer. By focusing on short cfDNA fragments, Cadex Genomics has developed a tumor-agnostic biomarker that is uniquely fit for purpose as a therapy monitoring tool.

To be able to detect small changes in cfDNA, Alibrex must be highly reproducible and have very low limits of detection to meet the performance necessary for clinical utility. We achieve this by targeting a non-coding region of DNA that has 1,800 copies in every cell and is located across all 23 chromosomes. Alibrex can detect differences in cfDNA levels in less than what is in a single cell.

Alibrex has been analyzed in two patient cohorts. The first, a study of 32 stage IV colorectal cancer patients at MD Anderson Cancer Center, demonstrated a sensitivity of 63% and specificity of 100%. A later multi-center study (74 lung, breast, and colorectal cancer patients) on an optimized version of the assay, demonstrated that Alibrex has a sensitivity of 88% and a specificity of 100%. By the end of August of 2023, we will have expanded this 74-patient analysis to 150 patients. Prior to making the test available to patients in the clinical setting, we will validate the assay in a 100-patient lung cancer study.

In clinical practice, we anticipate Alibrex being used monthly to determine if a patient is developing progressive disease and not responding to therapy. We do not anticipate Alibrex to be an imaging replacement; rather, we see the potential of imaging being used in significantly longer intervals.

In the future, with additional studies, Alibrex may potentially be used to monitor therapy in the neoadjuvant setting and to monitor prostate cancer patients who are in active surveillance.

Dr. Knopf is also Chief Medical Officer and Division Chief of Hematology and Oncology at Highland Hospital in Oakland, CA. He can be reached at



Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Common Sense Oncology: Moving Back Towards Outcomes that Matter

Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

Christopher M. Booth, MD, FRCPC
Medical Oncologist, Queen’s University, Kingston, Canada; Co-Founder, Common Sense Oncology

There are many ways to measure how well a particular cancer treatment works. But how much do these outcomes reflect a patient’s actual wellbeing? Our Curious Dr. George asks Christopher M. Booth, MD, FRCPC, one of the founding leaders of the new international initiative “Common Sense Oncology” (CSO), how CSO is working to improve patient outcomes.

Curious Dr. George: The practice of clinical oncology is difficult, at best, dealing every day with patients with potentially lethal malignancies. Some segments of oncology seem to have lost their way, veering towards the money-driven medicine that tempts physicians in many countries. How does CSO endeavor to put the patient at the forefront in the drive to maximize survival and enhance quality of life in an equitable manner, whilst giving serious attention to cost?

Christopher M. Booth MD, FRCPC: The art of oncology involves compassionate care, clear communication, and treatment that offers meaningful benefits.

Over the last four decades, transformative advances in surgery, radiotherapy, and systemic therapy have led to improved survival and quality of life for patients. However, in the last decade, a worrisome trend has emerged: most new cancer medicines do not help people live longer or better lives. Rather, the majority of new treatments approved by the U.S. Food and Drug Administration (FDA) are based on delaying tumour growth on a CT scan—usually measured as progression-free survival (PFS). In some circumstances, improvements in PFS are known to translate into improved overall survival (OS); however, these are the exception rather than the rule.

Hence, contemporary oncology is faced with a major challenge: most of our older treatments improve OS and/or quality of life, but most new medicines do not. This worrisome trend in our field is not well appreciated by patients or policymakers because our field has been consumed by hype—even for treatments that only have small benefits. The recent shift in our field to new medicines with marginal benefits is important because these treatments come with substantial costs: clinical toxicity for patients, time toxicity for patients and families, and financial toxicity to patients, families, and the health system.

These problems have developed due to a complex convergence of hope and money. Physicians and patients inherently look for treatment to provide benefit in what can be an overwhelming emotional journey. In many circumstances, a natural tension arises between hope and reality; this tension is most acute in the context of incurable cancer. In parallel, massive financial forces are involved in modern cancer medicine. These financial forces shape the research agenda and delivery of care. The pharmaceutical industry now funds about 90% of cancer drug trials, and a substantial proportion of industry revenues are directed into mass-marketing campaigns designed to increase use of cancer therapies—even if they are associated with marginal benefits.

In response to these challenges, an international group of oncologists, academics, and patient advocates gathered at Queen’s University in Kingston, Canada, in April 2023 to launch CSO. This grassroots initiative seeks to ensure all patients have access to cancer treatments that improve outcomes that matter, such as OS and quality of life. CSO’s mission, vision, guiding principles and action plan were recently published in the academic journal Lancet Oncology and on the Common Sense Oncology website. CSO is an inclusive movement that welcomes engagement from all stakeholders in the global cancer system. The voices of patients and patient advocates have been a core component of CSO since its inception. CSO promotes informed decision making with patients and seeks to promote health justice through access to high-quality and affordable cancer care.

The vision of CSO is that patients have access to cancer treatments that provide meaningful improvements in outcomes that matter, irrespective of where they live or their health system. To realize this vision, CSO has launched three streams of work related to evidence generation, evidence interpretation, and evidence communication.

Through our evidence generation efforts, CSO will work to ensure that clinical trials measure and report the impact of new therapies on outcomes that matter to patients. Evidence interpretation will involve educational initiatives to increase critical appraisal and critical thinking skills among oncologists. Our evidence communication initiatives will seek to improve understanding of cancer treatment risks and benefits among patients, the public, the media, and policymakers.

One of the primary goals in launching CSO was to provide a forum for the oncology community to have candid conversations about the successes and failures within our field.  CSO will celebrate well-conducted trials and treatments that measurably improve the lives of patients. However, the CSO community will also be willing to call out treatments that may cause more harm than good. Efforts to improve the generation, interpretation, and communication of evidence in our field will help move oncology closer to a reality in which all patients have access to high-quality treatment with meaningful benefits—regardless of where they live.

Dr. Booth is a medical oncologist and health services researcher at Queen’s University in Canada, where he holds the Canada Research Chair in Population Cancer Care. He can be reached at


Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

PARIS Test Uses Lab-Grown Mini-Tumors to Find a Patient’s Best Treatment

Curious Dr. George Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

Carla Grandori, MD, PhD
Founder and CEO of SEngine Precision Medicine

The U.S. Food and Drug Administration (FDA) has approved hundreds of drugs for the treatment of cancer. However, some approved drugs are more effective for certain patients than others. Our curious Dr. George asks Carla Grandori, MD, PhD, Founder and CEO of SEngine Precision Medicine, about her company’s test to detect which drugs are likely to be most effective for a given patient’s solid tumor.

Curious Dr. George: Too often, the FDA approves drugs that are not effective, and there is a serious lag from the beginning of their use until discovery that the drug is without benefit. For solid tumors, your company’s PARIS Test purports to detect which drugs will not work and which are likely to be effective. How exactly does it work? How might a physician and a patient access it?

Carla Grandori, MD, PhD: As physicians and patients unfortunately know firsthand, cancer treatment usually means a series of therapies over the course of years. Often a patient doesn’t respond to a course of treatment; sometimes they do, but disease later recurs anyway. It can feel like trial-and-error, with time slipping away and frightening degrees of uncertainty.

The concept of personalized medicine has generated a lot of excitement within the cancer community, with the implication that there has to be a way to figure out the best course of treatment for each individual. The field has made notable progress in certain cases, but most efforts are looking to define new buckets for patient cohorts, like carriers of a specific mutation. The DNA approach can find a therapeutic match for only 17% of patients’ DNA. That’s important, but how about the remaining 83% of patients? Also, often a patient’s cancer has multiple mutations—which one is actionable, and when? What about the many factors behind disease progression and the unique genetic background of each patient, all so complex to translate into therapies?

This leads to the most heartbreaking consideration: what if the best treatments for a specific patient sat ready in a pharmacy, but no one realized they were right? That’s what inspired us to create the PARIS Test, named for the warrior from Greek mythology who defeated his rival by finding the weakness in Achilles’ heel.

Our concept is to derive tumor organoids from a patient, so they reflect the actual characteristics of that individual’s disease, then use them to screen an array of potential therapies from our library of cancer drugs.

The way it works is, a patient or their care team shares some basic information with our CLIA-certified lab in Seattle, WA, so we can prepare instructions for an oncologist to collect appropriate biopsies (ideally four in total), surgical excision (~1 cm3), or body fluid ( more than 250 ml). Once we’ve received the sample, we use it to grow the 3D organoids, and leverage robotics to quickly screen hundreds of cancer drugs and combinations. Data produced from this process is analyzed through our informatics pipeline and combined with DNA sequencing for context, to produce an actionable report for oncologists with treatment recommendations and the rationale behind those choices. These reports get delivered to doctors in two to six weeks, and studies have shown their strong predictive power—more than 70% of patients’ clinical responses match the PARIS Test results.

Sometimes, the report confirms that the standard of care is the best way forward. But often we discover new options that can change a person’s life. One example we’re very proud of was summarized in a recently published case study for a patient we encountered who was in rapid decline and in hospice after failing standard-of-care treatments for her low-grade serous ovarian cancer (LGSOC). The PARIS Test identified the best course as a series of therapies that were approved as targeted lymphoma or lung cancer treatments, with little or no clinical evidence that anyone had even tried them in LGSOC. Through this personalized and targeted course of treatment, her symptoms reversed and she has experienced several years of stable disease.

Having now learned from hundreds of PARIS Test results from different patients, the most encouraging findings are that cancers, despite their chemoresistance, will still harbor unique sensitivities to very specific targeted treatments. Often, these unique cancer Achille’s heels are not obviously predicted from just DNA or RNA testing. These results and the many patients who have benefited from the PARIS Test indicate much hope for cancer patients—and the more medicines we will have, the higher the chance of finding a match for every patient’s cancer.

Dr. Grandori can be reached at


Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

How Would an Expert Manage His Own Advanced Bladder Cancer?

Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

Daniel E.C. Fein,
Genitourinary Oncologist and Researcher, Beth Israel Deaconess Medical Center; Instructor in Medicine, Harvard Medical School

When facing a frightening new cancer diagnosis, some people ask their doctors, “What would you do if you were me?” Here, our Curious Dr. George asks Daniel E.C. Fein, MD, how he would handle his own case of advanced bladder cancer. Dr. Fein is a genitourinary oncologist at Beth Israel Deaconess Medical Center (BIDMC) in Boston, MA, as well as an Instructor in Medicine at Harvard Medical School.

Curious Dr. George: Imagine a hypothetical scenario in which, as a non-smoking, very busy genitourinary medical oncologist, you were surprised to experience painless gross hematuria. Rapid subsequent microscopic urinalysis confirmed many red blood cells and some white blood cells. Urine cytology was suspicious for malignant cells, not otherwise specified. A complete blood count and blood chemistry panel were normal. At cystoscopy a sessile mass was found and biopsied, revealing a high-grade urothelial carcinoma. You then recognized a 10-pound loss of weight. The upper urinary tract was normal by imaging studies, but your pelvic lymph nodes were enlarged, and three suspicious lesions were found in your left lung. How would you proceed?

Daniel E.C. Fein, MD: Although I care for many patients with bladder cancer and have been intimately involved in the medical field for some time, I can only imagine how I might react to such shocking news. Why me? What did I do wrong? How should I tell my family? Do I need to take time off work? My mind would be spinning out of control.

I would try to take a deep breath and tell myself that it is likely that I have been diagnosed with an advanced bladder cancer. I would know that although this is likely incurable, there are new treatments available that can help me live longer and improve my quality of life. While establishing care with a cancer treatment team, I would reach out to my primary care doctor and therapist to disclose to them this new diagnosis and ask for the best way for me to manage my mental and physical health while beginning my journey.

Some background: Bladder cancer accounts for approximately 4% of new cancer cases in the US, with around 10% of those presenting with metastatic disease. Most cases are confined to the bladder and can be treated with resections and medicines instilled into the bladder. When cancer invades into the muscle of the bladder wall, patients can be potentially cured using a combination of treatments, such as chemotherapy followed by removal of the bladder, or chemotherapy with radiation. When bladder cancer has spread to distant sites outside of the area of the bladder (such as the lung) they are typically not curable but can be controlled with a combination of medications to help patients live in the range of years.

Before treatment: The approach to treating advanced bladder cancer is changing rapidly, with new approvals of medications and combinations coming out every year. Because of this, I would seek care at a nearby academic center that has experience treating bladder cancer using a multidisciplinary team of urologists, medical oncologists, and radiation oncologists.

I would undergo a biopsy of a lung lesion to confirm this is metastatic bladder cancer. I would direct this biopsy to be sent for molecular testing with a large gene panel specifically to look for mutations in genes such the FGFR2/3, which would tell me what kind of treatments I could receive in the future. I would also undergo germline genetic testing to see if I was born with a gene mutation that made me more likely to get this cancer and potentially others. I’d also ask if I should have any additional imaging, such as an MRI head or PET-CT, as this may be helpful for some patients.

Choosing treatment: Because of how quickly this field is changing, I would ask my care team if there were any clinical trials in my region with new and promising treatment combinations availableAs a member of the Innovation in Cancer Program at BIDMC, I have seen firsthand the outstanding care provided to cancer patients on clinical trials and would certainly participate in one if it was right for my cancer treatment and quality of life.

If I thought a clinical trial wasn’t right for me, I would ask if I could be a candidate for cisplatin-based chemotherapy. The two chemotherapy options here would be gemcitabine and cisplatin or dose-dense MVAC. If the cancer was controlled after four to six cycles of chemotherapy, I would ask if I should switch to avelumab as a maintenance treatment, which is an immunotherapy medication approved by the U.S. Food and Drug Administration (FDA) for this situation.

If I was unable receive cisplatin because of other medical conditions (such as poor kidney function, heart disease, or hearing loss), I would ask if I could receive the newly approved combination of enfortumab vedotin and pembrolizumab, which was recently granted accelerated approval by the FDA for cisplatin-ineligible patients. If I couldn’t receive this because of my medical conditions, I would consider alternatives such as carboplatin with gemcitabine, or pembrolizumab alone.

What next?: I may have challenges with managing side effects of therapy, coping with my new diagnosis and limited life expectancy, or sharing my experiences with friends and family members. I would seek assistance from a palliative care team and a local cancer support group who can focus on these mental, emotional, and physical challenges to improve my quality of life.

A new diagnosis of cancer, at any stage, can be life changing. If you are going through this, please know that you are not alone and that there are people around the world with and without cancer who have dedicated their lives to making yours better.

Dr. Fein can be reached at or on Twitter at @DFein_MD.


Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

Are You Getting Trustworthy Prostate Cancer Information?

When standard-of-care is an excuse for licensed medical malpractice

Are you getting trustworthy prostate cancer information? The terms standard-of-care, medical practice guidelines, FDA approved and, covered by insurance certainly seem very reassuring. But let’s see if some of these long-held beliefs about prostate cancer testing and treatment are dependable or whether they are simply untrue.

Curious Dr. George: Most people with prostate cancer live a long and healthy life. But some die, with or without treatment. It can be a confusing disease. To what extent are American men and physicians receiving trustworthy information about prostate cancer?

Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

Ronald Piana
Freelance science writer, specializing in oncology

Bert Vorstman, MD
Urologic Surgeon

The term prostate cancer.

Belief – All prostate cancers are deadly.

Evidence against the all-inclusive prostate cancer label – Prostate cancers are not all equally deadly. In fact, it’s mostly the 10 to 15 percent of high-grade, aggressive prostate cancers that are responsible for the 30,000 or so U.S. deaths annually.

Bottom line – The vast majority of men diagnosed with prostate cancer do not die of it. Furthermore, not only is the 10-year survival about the same whether treated or not but the 15-year survival rate, irrespective of treatment option, is about the same.

Prostate specific antigen (PSA) blood test.

Belief – The PSA test leads to early prostate cancer detection, early treatment and life-extension.

Evidence against PSA testing – The PSA has a false-positive rate of 78 percent because it is neither specific to the prostate or specific to prostate cancer; its so-called cut-off value of 0-4 n g/ml is an arbitrary and misleading metric; a PSA above 4 does not mean a diagnosis of prostate cancer; large prostates commonly generate high PSAs; the PSA value can be artificially raised or lowered without a cancer being present or progressing; the PSA cannot distinguish between aggressive and non-aggressive cancers; lowering the PSA does not lower a risk of cancer and, the subset of high-grade, aggressive and potentially deadly prostate cancers may produce little to no PSA and can go undetected. Incomprehensibly, although the reliability of the PSA was concerning from the outset, the FDA (Food and Drug Administration) approved the PSA test for prostate cancer screening in 1994. Unsurprisingly, in 2009 urologists clinical studies determined that PSA testing failed to save significant numbers of lives. More damning, the USPSTF (United States Preventive Services Task Force) gave PSA-based prostate cancer screening a “D” grade in 2011 concluding that, “the benefits do not outweigh the harms”. Shamefully, after pressure from self-interest groups the USPSTF “D” grading was watered-down to an ineffectual “C” warning in 2018.

Bottom line – PSA-based screening – includes the inaccurate digital prostate exam or digital rectal exam (DRE) – is highly unreliable, risky and fails to save significant numbers of lives. In fact, many cancers are detected by chance during evaluation for an elevated PSA as the PSA was generated by the BPH and not the cancer. Currently, there is no blood or urine test that can detect just high-grade prostate cancer reliably.

The ultrasound-guided prostate needle biopsy.

Belief – That an ultrasound-guided prostate needle biopsy can reliably detect a potentially deadly prostate cancer.

Evidence against the ultrasound-guided prostate needle biopsy – 1. Prostate cancer is commonly a multifocal disease – meaning that areas of cancer can arise in several different areas of the prostate at the same time or, later. Yet, so-called standard practice for detection calls for the use of an ultrasound, which can’t see the cancer and then randomly and blindly biopsy the prostate 12 times with a needle to evaluate whether or not a cancer is present. When the volume of these 12 needle cores is measured against the volume of an average prostate, only about 0.1 percent of the prostate ends up being sampled. It also means that the clinical state of the 99.9 percent of the un-sampled prostate remains unknown. Even if 120 biopsies were taken (10 times the standard number of 12) you would still be clueless about 99.0 percent of the prostate. 2. There are two techniques for prostate biopsy: transrectal or transperineal (with or without a template). The transrectal approach is riskier than the transperineal and is associated with potentially serious complications of sepsis and bleeding. 3. The concern about false negatives (missing cancers) is hardly surprising when only 0.1 percent of the prostate is sampled. The transrectal approach has recorded a false negative rate of more than 33 percent. On the other hand, others have claimed to find 6 percent more cancers using the transperineal route. Possibly because of the compressive effects on the prostate and the angle at which the transperineally placed needle enters the prostate.

Bottom line – The ultrasound-guided needle biopsy test is risky and embarrassingly unscientific because of its egregious sampling error. The perineal approach is less risky but equally unscientific. Additionally, there is no hard evidence that either technique detects significant numbers of the 10-15 percent of the potentially lethal high-risk tumors. However, the best current screening tool to detect significant cancer anywhere in the prostate is the non-contrast MRI conducted by a radiologist with expertise in MRI prostate imaging. Areas judged to be consistent with PI-RADS four or five disease on the MRI are suggestive of potentially lethal high-grade disease and can be confirmed with an MRI-guided targeted biopsy.

The Gleason grade and score.

Belief – A pathologist’s interpretation of what is judged to be a certain grade of cancer under the microscope is reliable.

Evidence against Gleason grading reliability – The Gleason grading and scoring system is complex and relies overly on a pathologist’s knowledge and interpretive skills for estimating what grades of cancer they believe to see under low-power microscopy. Because of potential errors of judgment, grade misclassifications and disagreements amongst pathologists are common – underscoring a profound lack of reproducibility of the Gleason system.

Bottom line – Patients can never be absolutely sure of their prostate cancer grades and scores. Getting a second opinion from an experienced prostate cancer pathologist and undertaking a screening non-contrast MRI of the prostate with an expert is appropriate.

The Gleason grade 3 and the 3+3=6 “cancer”.

Belief – The Gleason grade 3 (in the Gleason 3+3=6) is a “cancer”.

Evidence against the Gleason grade 3 being a cancer – Initially, the Gleason grade 3 appearance under low-power microscopy was thought to be consistent with an early low-grade, low-risk cancer. However, since then, both the clinical evidence and the fact that the genetic pathways enabling cancer development and spread are turned off indicate that the Gleason grade 3 lacks the features of a cancer.

Bottom line – The Gleason grade 3 fails to behave as cancerous since it is not a cancer. Shamefully, the grade 3 (3+3=6) is still labeled as a cancer, scaring untold numbers of patients towards unnecessary investigation and harmful treatment. Rather, the grade 3 disease appears to be simply a benign feature of aging.

Imaging for the staging of prostate cancer.

Belief – That bone scans, ultrasounds and CT scans can determine whether a cancer is localized or has spread.

Evidence against bone scans, ultrasounds and CT scans for staging – Bone scans, ultrasounds and CT scans are quite insensitive for detecting small volume cancer spread making their use in staging unreliable. Underscoring this concern is the fact that prostate cancer cells have been found in the bone marrow of patients with so-called localized disease. These metastases may begin when high-grade cancers are as small as 0.25 mm in size and barely detectable within the prostate.

Bottom line – Staging of prostate cancer using bone scans, ultrasounds and CT scans is unreliable due to their insensitivity. The PMSA PET/CT scan and the whole body diffusion MRI studies have greater reliability for detecting small-volume spread to lymph nodes and bones. 

Prostate cancer surgical “treatment”.

Belief – That cutting out prostate cancer – whether open or robotically gets rid of it and “saves lives”.

Evidence against surgeryH.H. Young M.D. claimed early diagnosis, cure and “the remarkably satisfactory functional results furnished” from his surgical technique. In contrast, he gave zero evidence for early diagnosis or cure, two patients died and the other two were left with lifelong urinary leakage. And, when robotics entered the business of surgery not only was the device given an FDA approval without demonstrating clear benefits but the FDA’s fallacious 510(K) process was then manipulated to permit use of the tool in radical prostate surgery. Again, without sufficient evidence for safety or benefits. Unsurprisingly, the robotic prostatectomy has a similar incidence of residual cancer (positive margins occurred in 11- 48 percent of patients) and a similar incidence of impotence and incontinence to open surgery. These complications are common and typically managed with radiation, counseling and rehabilitation programs or, implantable devices for ongoing limp and leaking issues. The breakdown of these gadgets often results in more surgery, costs and suffering. In fact, the number of complications associated with the robotic device is highlighted in the FDA’s MAUDE (Manufacturer and User Facility Device Experience) site which recorded a great increase in adverse events. Irrationally, radical prostatectomy is still considered standard-of-care despite physicians concluding in 2012 that surgery failed to save significant numbers of lives. And, despite the evidence against surgery, the SPCG4 article and its conclusion “Radical prostatectomy was associated with a reduction in the rate of death from prostate cancer”, is often quoted by urologists to support their opinion that radical prostatectomy saves lives. Aside from this work recording a substantial number of impotence and incontinence complications, the study is also flawed because of the commingling of participants with various Gleason grades and scores (both well differentiated and moderately well differentiated), unknown tumor volumes and the arbitrary use of anti-androgens in others – issues that can skew results. Additionally, the relatively short follow up time for this study (15 years) is troubling since the particular prostate cancers that the researchers targeted grow very slowly. For the low Gleason score/low-risk/well-differentiated, grade 1 tumor a mean cell doubling time of about 577 ± 68 days has been recorded. This figure means that it can take some 40 years or more from the time of cell mutation for the cancer to reach a diameter of 1 cm and be big enough to be felt on manual prostate examination. Clearly, such a slow cell division rate and a median follow up time of 12.8 years can only deliver a semblance of cure.

Bottom line – Cutting out prostate cancer whether by robotic or open techniques is unsafe and fails to save significant numbers of lives. Worse still, life extension has not been demonstrated for any focal or whole-gland prostate cancer treatment options. In part, because most, if not all, studies are flawed by the inclusion of participants with the bogus Gleason 6 “cancer”, incorporating patients with dissimilar Gleason grades, scores and tumor volumes, reliance on insensitive staging methods and, arbitrarily treating others with testosterone suppression.

Active surveillance for low-risk prostate cancer.

Belief – That by using 6 monthly PSAs, 12 monthly DREs, 12 monthly biopsies (a random 12-core) and maybe a 12 monthly MRI urologists can assess if a low-risk prostate cancer was progressing and required treatment. Urologists initiated this program for monitoring low-risk disease after appreciating the facts that most prostate cancers grow slowly and that the treatments were often worse than the disease. Enthusiastic support also came from the NIH.

Evidence against active surveillance – 1. PSA testing (and all other tests incorporating the PSA), DREs and 12-core biopsies (whether transrectal or transperineal) are highly unreliable as detailed above. 2. A prostate cancer diagnosis was likely established on the basis of a 0.1 percent random and blind sampling of the prostate. The follow up biopsy is likely done in exactly the same way. Clearly such an unscientific process can fail to detect a cancer, is unable to target reliably the original cancer and determine if the original cancer has “progressed” or, whether the cancer now detected was already present but missed by the previous biopsy. 3. Since non-contrast MRIs of the prostate (by a radiologist experienced in prostate MRI imaging) are able to examine the whole prostate and reliably identify the 10-15 percent of potentially lethal cancers their use has become more common. However, not all MRI’s are equal. Although MRI-guided targeted biopsies have been recorded as being dependable, most prostate needle biopsies are not undertaken using MRI-guided targeted techniques but by urologists using “fusion” studies. There are a number of concerns associated with the reliability of this fusion method. The MRI is commonly undertaken by a radiologist of unknown experience, knowledge and interpretative ability for PI-RADS findings – PI-RADS 4 or 5 changes on the MRI may reflect potentially lethal disease. However, this PI-RADS classification, like the Gleason grading and scoring system, is complex and has concerns for errors of interpretation. Additionally, the quality of the MRI study generated can be impacted by the radiologist’s particular study methodology, the particulars of the MRI machine and its software. Then, this previously recorded MRI study is “fused” with the ultrasound study on the day that the prostate biopsy is undertaken. Now, there are additional concerns relating to the type of ultrasound machine to be used and the ability of the urologist to interpret the images. Once “suspicious” areas are “identified” with this fusion method they can be targeted for biopsy. Absurdly, many urologists will add a random biopsy sampling 0.1 percent of the prostate to the targeted biopsy of the high-risk area located in the fusion study. This additional biopsy may only increase the risk of complications and the detection of non-lethal disease. Also bothersome, although MRI-guided targeted biopsies of PI-RADS 4 and 5 areas by radiologists may be more reliable, the fusion technique keeps the biopsy (and revenue) in the hands of urologists. 4. The definitions used to determine “progression” of low-risk disease are variable, unreliable and also impacted by laboratory and observer error – PSA level, PSA velocity or density, clinical staging, DRE, biopsies, Gleason grades and scores, tumor volumes and the number of positive cores and core lengths – none truly reflect what’s happening in the entire prostate. 5. PSA testing and surgical treatment do not save significant numbers of lives. 6. Whether you are treated or not the 10 year survival is about the same.

Bottom line – Clearly, misinterpretations about the presence or absence of cancer, stability of a low-risk cancer or the “progression” of disease are inevitable because of multiple inaccuracies. The potential benefits of active surveillance for low and moderate risk prostate cancer and the saving of significant numbers of lives because of so-called “timely” identification of disease progression have not been supported by hard data. This is not surprising when a number of highly unreliable tests are conflated to generate an unreliable endpoint before initiating a treatment option for which there is no evidence that significant numbers of lives are saved.

Why prostate cancer information is untrustworthy.

PSA-based testing and prostate cancer surgery are both risky and fail to save significant numbers of lives. How then, did the standard-of-care dogma about prostate cancer testing and treatment become so disconnected from the clinical evidence?

Meta-researcher John Ioannidis M.D. discovered the likely cause of this uncoupling of treatment beliefs from the evidence after reviewing multiple healthcare papers. He concluded that “most published research is false”. False, because most studies were commonly not founded on sound scientific principles and corrupted by errors of judgment, approximations, opinions, assumptions and conflicts-of-interest. Making this “research information” more suspect was the inevitable manipulation of study design and results by sponsoring organizations to produce “facts” supporting their biases.

Reliable healthcare information can only be developed from data sourced from studies delivering irrefutable and reproducible results. In contrast, much of the material used to develop the guidelines for prostate cancer management came from very poorly designed studies and beliefs. An all too common junk science that results in prescriptions for care that are untrustworthy, commonly exploitative and make a mockery of the Hippocratic Oath.

More references.

The Great Prostate Hoax by R. Ablin and R. Piana.

The Rise and Fall of the Prostate Cancer Scam by A. Horan M.D. 


This article is dedicated to Anthony Horan MD, a urologist and author (The Rise and Fall of the Prostate Cancer Scam) who fearlessly challenged the culture and the business of prostate cancer. He was always on the right side of what should never have been a controversy. Sadly, the prostate cancer testing and treatment industry is a 32.7 billion dollar market for which there is no hard evidence that significant numbers of lives are being saved.


Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

The Sordid “Truth” about Prostate Cancer

Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

Ronald Piana
Freelance science writer, specializing in oncology

Bert Vorstman, MD
Urologic Surgeon

Prostate cancer has long been one of the most common types of cancers in American men. Our Curious Dr. George asks retired urologic surgeon Bert Vorstman, MD, and freelance science writer Ronald Piana about the quality of prostate cancer information available to U.S. patients and doctors.

Curious Dr. George: Most people with prostate cancer live a long and healthy life. But some die, with or without treatment. It can be a confusing disease. To what extent are American men and physicians receiving trustworthy information about prostate cancer?

Bert Vorstman and Ron Piana: For men entering the prostate cancer arena, the terms “standard-of-care,” “medical practice guidelines,” and “FDA-approved” are very reassuring. But are they trustworthy? Let’s see if the evidence supports the stamp of standard practice:

  • In 1994, the U.S. FDA (Food and Drug Administration) approved the PSA (prostate specific antigen) test, despite the fact that it had a false-positive rate of 78 percent because it is neither specific to the prostate nor to prostate cancer. As well, its so-called cut-off value of 0 to 4 ng/mL is an arbitrary and misleading metric that can lead to unnecessary and potentially harmful therapies. Along with a host of other PSA inaccuracies, the 10 to 15 percent subset of prostate cancers that are high-grade and potentially deadly can be missed as they often produce little to no PSA—a major problem, since it’s essentially these aggressive prostate cancers that are responsible for the 30,000 or so U.S. prostate cancer deaths annually.
  • The 12-core ultrasound-guided prostate needle biopsy samples only about 0.1 percent of the prostate blindly and randomly. Along with this egregious sampling error, the biopsy exposes men to the risk of significant complications of sepsis and bleeding.
  • Examination of a prostate biopsy under low-power microscopy overly relies on the pathologist’s knowledge and interpretive skills of the complex Gleason grading and scoring system. Because of potential errors of judgment, grade misclassifications and disagreements about a given patient’s diagnosis amongst pathologists are common.
  • The Gleason grade 3 (in the 3+3=6) was judged initially to be consistent with a low-grade, low-risk cancer under low-power microscopy. However, clinical evidence—and the discovery that the genetic pathways enabling cancer development and spread are inactive—mean that grade 3 has features inconsistent with a cancer.
  • The safety and benefits of prostate cancer surgery were always in doubt. In 1904, H. Young MD claimed early diagnosis, cure, and remarkably satisfactory functional results from radical prostate surgery. However, he gave no actual evidence for early diagnosis or cure, two patients died, and the other two were left with lifelong urinary leakage. And, when robotics entered the business of surgery, not only was this approach given an FDA approval without demonstrating clear benefits, but the FDA’s fallacious 510(K) process was manipulated to permit use of the device for radical prostatectomy—again, without sufficient evidence of safety or benefits. Unsurprisingly, robotic prostatectomy, like open surgery, had a similar rate of residual cancer, incontinence and impotence problems. These complications were managed with radiation, pre- and post-operative counseling and rehabilitation programs, or implantable devices for ongoing limp and leaking issues. The breakdown of these gadgets resulted in even more surgery, costs, and suffering.

Warning: Prostate cancer testing and treatment are unreliable, unsafe, and fail to extend life. Since most men outlive their prostate cancer, and prostate cancer information is untrustworthy, vulnerable and unwitting men are in great jeopardy of being harmed.

For more invaluable information for patients and physicians on the unreliability of prostate cancer testing and treatment, readers can consult the books The Great Prostate Hoax by Ronald Piana and Richard J. Ablin, PhD, and The Rise and Fall of the Prostate Cancer Scam by A. Horan M.D.

Ronald Piana can be reached at and Dr. Vorstman at

Related links:


Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

A New Biomarker to Optimize Immunotherapy for People with Cancer

Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

Scott Tomlins, MD, PhD
Co-founder & Chief Medical Officer, Strata Oncology

Immunotherapy—a type of treatment that harnesses a patient’s own immune system to fight cancer—has been a “game changer” for many patients. It can be difficult, however, to predict whether or not a given person would benefit from immunotherapy, especially when it comes to drugs that target the immune system molecules PD-1 and PD-L1. Our Curious Dr. George asks Scott Tomlins, MD, PhD, Co-founder and Chief Medical Officer of Strata Oncology, about his company’s new tool to help ensure that anyone who could benefit from these drugs is identified.

Curious Dr. George: One predictor of response to immunotherapy, tumor mutation burden (TMB), has been very helpful for patients whose tumors have a high TMB score. But the tumors of many other patients may also respond to immunotherapy, providing substantial benefits in both progression-free and overall survival. What is Strata Oncology’s Immunotherapy Response ScoreTM (IRSTM), how effective is it, and how can patients with solid tumors access it?

Scott Tomlins, MD, PhDCurrent biomarkers for immunotherapy are not enough. Immune checkpoint inhibition with monoclonal antibodies targeting PD-1 and PD-L1 has revolutionized the care of patients with advanced cancer. TMB is an important pan-tumor biomarker for anti-PD-1/PD-L1 therapy, but it does not identify most patients who benefit.

For example, let’s look at the KEYNOTE-158 study of 10 tumor types that led to pan-solid tumor approval by the U.S. Food and Drug Administration (FDA) of second-line pembrolizumab monotherapy in patients who are TMB-high (TMB-H). While a higher objective response rate (ORR) was observed in TMB-H patients versus TMB-low (TMB-L), numerically more objective responses were observed in TMB-L patients (43 out of 688 in TMB-L versus 30 out of 102 in TMB-H). This study demonstrates that TMB alone is not sufficient to identify all responders.

Likewise, in an analysis of TMB in 1,772 patients treated with pembrolizumab monotherapy across 24 tumor types, although ORR was significantly higher in TMB-H versus TMB-L patients, numerically similar numbers of responding patients were again observed (136 out of 433 in TMB-H versus 127 out of 1339 in TMB-L).

Clearly, there is more to the story when it comes to who will benefit from anti-PD-1/PD-L1 therapy. An improved predictive biomarker is needed to ensure that all patients who can benefit from immunotherapy are given the opportunity.

In our recent publication in Communications Medicine, we describe the development, validation, and clinical utility of a new biomarker that fulfills this unmet medical need—the Immunotherapy Response Score or “IRS”.

Immunotherapy Response Score (IRS) is an improved predictive biomarker

IRS combines TMB with four target gene expression measurements (PD-L1, PD-1, TOP2A, and ADAM12) from simultaneous, analytically valid, comprehensive genomic profiling (CGP) plus quantitative transcriptional profiling (qTP) of formalin-fixed paraffin-embedded (FFPE) tumor specimens.

We developed IRS using molecular profiling data combined with treatment and outcome data from the Strata Trial® (NCT03061305), an ongoing observational clinical trial evaluating the impact of molecular profiling for patients with advanced solid tumors.

IRS was trained to predict real-world progression-free survival (rwPFS, by time-to-next-therapy) in a discovery cohort (26 tumor types) of patients treated with pembrolizumab systemic therapy and was then validated in an independent cohort (24 tumor types) of patients treated with non-pembrolizumab anti-PD-1/PD-L1 monotherapy.

In the validation cohort, IRS-high (IRS-H) versus IRS-low (IRS-L) patients had significantly longer anti-PD-1/PD-L1 monotherapy rwPFS (median rwPFS 23.1 months versus 10.2 months, adjusted hazard ratio = 0.52) and overall survival (OS; median OS 40.4 months versus 21.4 months, adjusted hazard ratio = 0.49).

The predictive nature of IRS was confirmed in a case-crossover analysis of 146 patients from the pembrolizumab cohort who had received a previous line of systemic therapy prior to pembrolizumab monotherapy, and by a lack of association with rwPFS in 3,184 patients treated with a non-anti-PD-1/PD-1 or anti-CTLA4 containing first line systemic therapy.

IRS-H/TMB-L patients had similar outcomes as IRS-H/TMB-H patients, demonstrating the clinical utility of IRS beyond TMB alone. Across all Strata Trial patients, IRS-H identified a population nearly twice the size of the TMB-H population (n=24,463; 20.9% versus 10.8%). Critically, 7.6% of patients with tumor types not approved for PD-1/PD-L1 monotherapy were IRS-H/TMB-L, representing a sizable population predicted to have benefit but not currently eligible for treatment.

Bringing new options to people with cancer

We are excited to put this novel biomarker into the hands of physicians to help them ensure every patient gets their best-possible therapy. We are currently providing early access to IRS to a select group of key opinion leaders. IRS will be more broadly available later in 2023.

IRS is just the beginning. By leveraging data from tens of thousands of patients collected under the Strata Trial protocol we are discovering, validating, and demonstrating clinical utility for multiple new, highly quantitative, DNA- and RNA-based multivariate predictive treatment selection biomarker algorithms that span therapeutic modalities.

Dr. Tomlins can be reached at

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

Learnings from Pilot Study: Creating Treatment Templates to Serve More Glioblastoma Patients

Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

Adrienne Nugent, PhD
Cancer Commons Senior Scientist

A recent pilot study between Cancer Commons and the Musella Foundation for Brain Tumor Research & Information is identifying patterns that are being translated into treatment templates to better serve a larger group of GBM patients. Our Curious Dr. George asks Cancer Commons Scientist Adrienne Nugent, PhD, to discuss key factors that point to the best courses of action a patient might take, and about the clinical utility of a Virtual Tumor Board.

Curious Dr. George: Patients with postoperative Glioblastoma multiforme (GBM) are among the most difficult oncology cases to manage. In your work as a Clinical Scientist at Cancer Commons you have worked directly with many such registered patients/clients who seek the information and options that may help them. You coordinate neuro-oncologists who may constitute Virtual Tumor Boards. What are the key factors you seek to identify to determine what courses of action a patient might take and whether a Virtual Tumor Board may be helpful? Is a template useful?

Adrienne Nugent, PhD: As a Cancer Commons scientist, I feel very grateful to be able to work with such wonderful and inspiring patients and caregivers on a daily basis. The patients and families who have been handed the especially difficult diagnosis of Glioblastoma face myriad decisions and challenges due to the aggressive nature of the disease and the fact that the standard of care (SOC) treatment has not changed all that much since 2005.

Given the current outcomes with SOC, patients are encouraged to look for clinical trials and novel treatment options, but quickly face many barriers to accessing and enrolling in these more promising therapies. This lack of access to the latest developments in medicine and technology reflects a growing gap between many cancer patients and optimized precision cancer treatment.

To try and bridge this gap, Cancer Commons partnered with the Musella Foundation for Brain Tumor Research & Information to launch a pilot study for GBM patients. We provided 10 patients with complete review of their medical history by a Cancer Commons scientist and a virtual tumor board (VTB) comprised of three neuro-oncologists. The scientist identified a list of evidence-based treatment options and the VTB provided their recommendations based on a unique combination of factors for that patient.

Many valuable patterns emerged from this initial pilot study that we are now translating into treatment templates to better serve a larger group of GBM patients. The key features we’ve identified for creating templates of prioritized treatment options include:

  • Location of the tumor(s): Tumors on the brain stem or involving leptomeningeal metastases are frequently excluded in clinical trials or have unique trials specifically for these conditions
  • Eligibility for surgery and/or radiation: Some clinical trials involve a combination of systemic therapy, surgery, and/or radiation. Eligibility for further surgery or radiation must be determined by the treating neuro-oncologist, neurosurgeon, and radiation oncologist
  • Treatment line: Newly diagnosed, on SOC or adjuvant therapy, at progression/recurrence, or on later-line treatment
  • KPS/ECOG: Patient performance status based onKPS (Karnofsky Performance Status) or ECOG (Eastern Cooperative Oncology Group) scale. Most clinical trials will only accept patients with ECOG <2 or KPS >60 or 70
  • Tumor biomarkers: MGMT methylation status, EGFR/PTEN/TERT alterations, NTRK/ROS1/FGFR oncogenic fusions, tumor mutation burden, PD-L1 expression
  • Treatment history: Some trials restrict patients with specific prior treatments. In particular, prior Bevacizumab/Avastin treatment excludes patients from many, but not all, clinical trials
  • Geographic location of the patient: Prioritization of trials near the patient’s home with the option for regional or nationwide trial search given the ability of the patient to travel
  • Patient goals and quality of life: Prioritization of trials to meet the desires of the patients, such as identifying trials that avoid randomization to SOC, avoid chemotherapy at recurrence, require fewer hospital/clinic visits, involve oral rather than infusion treatments, etc.

When these features are known, we feel most GBM patients can benefit from our templated treatment recommendations without needing to convene a full VTB. However, VTBs can be particularly helpful for patients who do not have access to neuro-oncologists or are receiving conflicting information, such as if more surgery or radiation are indicated or if they have progression versus pseudoprogression. In these cases, a VTB can yield valuable insights to resolve open questions.

Dr. Nugent can be reached at

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

Using Live Cells from Patients to Find the Right Cancer Drug

Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

Clifford A. Reid, PhD
CEO, Travera

Today, many cancer patients benefit from targeted drugs that are matched to the distinct genetic mutations found in their tumors. However, especially in late-stage cancer, this “precision oncology” strategy has not proven to be as transformative as people once hoped. Here, Curious Dr. George asks Clifford A. Reid, PhD, CEO of Travera, how his company is addressing this problem.

Curious Dr. George: The U.S. Food and Drug Administration (FDA) has approved about 270 anti-cancer drugs. The National Comprehensive Cancer Network publishes guidelines for treatment of about 61 major cancer types. There is consensus on 1st– and 2nd-line therapy for most, but great divergence on best 3rd-line treatment. Precision oncology based on population studies not only usually fails but is a false premise. What is Travera doing to convert the promise of effective and efficient targeted drug therapy into reality?

Clifford A. Reid, PhD: The original goal of what we now know as “precision oncology” was to understand the root genetic cause of each cancer, and then design a set of targeted drugs to attack each of these cancer-causing DNA mutations. At the time, this was called “personalized oncology,” and its promise was to deliver “the right drug to the right patient at the right time” based on the DNA mutations in each cancer. Unfortunately, this approach has not worked. While the cancer research community has identified hundreds of cancer-causing DNA mutations, drugs that target these mutations inexplicably don’t work for many patients that have the targeted mutations. To our great disappointment, the promise of personalized oncology is not being realized by these genetically targeted drugs.

A small part of the cancer research community has long recognized that it is simply impossible for the results of a clinical trial to generate personalized therapies for each individual patient. Clinical trials are fundamentally designed to include a population of “similar” patients, and get drugs approved for that population. But we know that cancers are highly heterogeneous, especially in late-stage patients, and that no “one size fits all” result of a clinical trial can address each individual patient’s unique cancer.

That part of the cancer research community has focused on developing tests that directly measure the response of an individual’s live cancer cells to a large set of cancer drugs. This direct-measurement approach not only incorporates everything we know about how cancers and cancer drugs work, but also incorporates everything we don’t know. It simply tries a variety of cancer drugs on each patient’s live cancer cells to find the drug or drug combination that will work for that patient at that moment in time.

While this direct-measurement approach may seem quite obvious, as it works beautifully for selecting the right antibiotics for patients with bacterial infections, it has never really worked in cancer, despite decades of efforts. The fundamental problem is that cancer cells, which are so robust inside a patient, become extremely fragile when removed from the patient, and typically die before most cancer drugs can be tested against them. Efforts to keep the cells alive long enough to test them have backfired: cancer cells forced to stay alive change how they respond to cancer drugs, and no longer behave like the cancer cells inside the patient.

Travera is the first company to develop a test that is fast enough to measure the response of cancer cells to cancer drugs without having to force the cancer cells to stay alive for many days outside the patient. Using a new measurement tool invented at the Massachusetts Institute of Technology (MIT), Travera measures the weight change of individual cancer cells in response to cancer drugs. It turns out that for most cancers and most cancer drugs, if the drug is going to kill the cancer cells in a few days, then it changes the weights of the cancer cells in a few hours, but by an amount too small to be detected prior to the MIT invention. Travera uses this exquisitely sensitive measurement tool to offer its Rapid Therapy Guidance test with 2-day turnaround time and high predictive accuracy. The test is now available for most cancers (including all carcinomas) and for over 100 FDA-approved cancer drugs.

For more information, please visit Travera at

Dr. Reid can be reached at

Curious Dr. George | Plumbing the Core and Nibbling at the Margins of Cancer

How Would an Expert Manage His Own Advanced Hodgkin Lymphoma?

Curious Dr. George
Cancer Commons Editor in Chief George Lundberg, MD, is the face and curator of this invitation-only column

Chief of Oncology, Alameda Health System; Institute for Health Policy, University of California San Francisco

When facing a frightening new cancer diagnosis, some people ask their doctors, “What would you do if you were me?” Here, our Curious Dr. George asks oncologist Kevin Knopf, MD, how he would handle his own advanced Hodgkin lymphoma.

Curious Dr. George: Please consider this hypothetical scenario: as a very busy practicing clinical oncologist during the COVID-19 pandemic, you were not paying much attention to your own health when you noticed a weight loss of 7 pounds, a dry cough, and a little fever and sweating at night. Your home COVID-19 antigen tests were negative, but you found some enlarged cervical lymph nodes. Your physician confirmed the lymphadenopathy and palpated an enlarged spleen. Your hematocrit was 39, and WBC 16, 000. CT scan detected both para aortic and mediastinal lymphadenopathy. Biopsy of a cervical node was diagnosed as nodular sclerosing Hodgkin lymphoma. How do you proceed?

Kevin Knopf, MD, MPH: First, which chemotherapy regimen would I pick, given the treatment is with curative intent? Three standard choices: ABVD, BEACOPP, and A-AVD foster intense debate amongst oncologists. A recent Twitter poll by Dr. Aaron Goodman (of the University of California, San Diego) had opinions split evenly between R-CHOP, R-BEACOPP, and A-AVD. The choice has subtle nuances; my feeling is ABVD is probably fine for young patients where the risk of bleomycin pulmonary toxicity can be monitored closely; for myself I would choose A-AVD and monitor carefully for neuropathy.

Where to be treated? Where I live in the East Bay of California’s San Francisco Bay Area, there are centers for the University of California, San Francisco (UCSF) and Stanford, and Dr. Andreadis—a friend—is at UCSF, and Dr. Barbara Galligan, my former resident whom I helped mentor into oncology, are all excellent. By a thin margin I would choose Dr. Rajesh Behl in Berkeley in the East Bay. He is a smart oncologist and I appreciate his dry sense of humor. Getting in and out of his office for treatment would be easy, and it is with the infusion nurses that I would spend 98% of my time.

I am fortunate that my insurance would cover the complete cost and my choice of physicians, but this illustrates an area of oncology I spend a lot of time thinking and writing about: cost effectiveness and health equity. There are broad disparities in cancer care—within the U.S. and worldwide—such that many patients with a curable cancer, such as Hodgkin lymphoma, are not cured.

Pricing for cancer care seems arbitrary and is not really negotiated. In classic economics, one would pick amongst my 5 treatment options based on the lowest cost of care, as the outcome is almost certainly equal. There is a mind-blowing aspect of American health insurance: when Obamacare was enacted, insurance companies’ net profit was capped at 15% of the medical loss ratio, meaning the more my insurance company spends, the more money they can make. My premiums have jumped 15% in 2023. A-AVD is 108-fold more costly than ABVD. Cancer care in the U.S. is virtually “all accelerator, no brake,” and the cost of care keeps rising each year, and health disparities widen.

Sociologist C. Wright Mills quipped “the most important thing you can do in a capitalistic society is choose the right parents.” I chose wisely and ended up with “Cadillac” health insurance. All other industrialized nations have a single-party payer system to pay for care, while U.S. health care delivery is based on a for-profit model. American health care works out well in this particular hypothetical example, but overall, we rank about 50th in the world in terms of healthcare efficiency—tied with Bulgaria.

There are casualties. Half of the U.S. has medical debt, 50% of women with metastatic breast cancer are being pursued by debt collectors, and 42% of newly diagnosed cancer patients will go bankrupt within 3 years of diagnosis. We have a tragic and widening cancer disparity gap in the U.S. and a large care gap between first-world nations and low- and middle-income countries. In many parts of the world, a similar patient would not receive curative chemotherapy. People speak of the American health care “system,” but that would imply a formal interconnected design rather than our Byzantine way of paying for health care. So I might come out of this diagnosis just fine, and not bankrupt, but that was just a simple twist of fate.

Dr. Knopf can be reached at