Genitourinary cancers come in all shapes and sizes, and this year, ESMO2023 takes the research up a notch. Prostate cancer is centre stage, and you might ask why, as it boasts extraordinary overall survival and progression-free survival. The issue lies in the sequencing of therapies and how to make treatment durable and better tolerated for all. Third, immunotherapy is not ready for primetime in this cohort of patients, and the reasons are unclear. Not to be outdone, bladder cancer continues to make strides in patient care with a phase 1 study that may be lost in no-man land or could harbour a shift in trial design with antibody-drug conjugates. Today, we discuss the following trials:

Welcome back to Oncology for the Inquisitive Mind's ongoing coverage of ESMO 2023. In the spirit of a worldwide oncology conference, here we present results from three very exciting trials in the early breast phase. Will immunotherapy begin to carve out a niche in early, high-risk, ER-positive breast cancer? Can atezolizumab demonstrate a benefit in early TNBC, and expand its own territory? Is abemaciclib pulling away from its rivals in the treatment of high-risk, ER-positive breast cancer? Will managing early breast cancer eventually have a similar success rate to the management of diabetes? And, most importantly, is Michelangelo a better Ninja Turtle than Donatello? The answers to all these questions, and more, lie within.

Every so often, an area of medical oncology has so many interesting presentations at a seminal conference that it becomes impossible to leave them out. At such times, Josh and Michael merely shrug their shoulders and say "why don't we do all of them." ESMO 2023 is one such instance. Despite their best efforts, our intrepid duo were unable to narrow down their presentation of early breast cancer highlights to one episode, so they are going to do two (for the price of one).

ESMO 2023 showcased several promising trials in the small-cell lung cancer space. A cancer that continues to send shivers down the spine of budding oncologists for decades. Today, we look at several different classes of drugs, the first being a novel immunotherapy agent, the second a well-known antibody-drug conjugate and the third a synthetic alkaloid analogue. Lurbinectedin and pembrolizumab, sacitizumab govitecan or toripalimab, while all difficult to say five times fast, may change the future of small cell lung cancer. Which is your drug of choice? Tune in to find out if you chose correctly!

Michael and Josh continue their examination of the crème-de-la-crème of the European Society of Medical Oncology conference of 2023. Today they focus on metastatic breast cancer, with a particular focus on antibody-drug conjugates (ADCs). T-Dxd, Dato-Dxd and trastuzumab duocarmazine are just three of the many novel agents in this space, and likely represent part of the future (and the present) of medical oncology. How effective are these treatments? Will the final results of the TULIP study blossom like its namesake? Will T-Dxd fulfil its DESTINY and become a treatment option for HER-2 low advanced breast cancer? Will Dato-Dxd assist in making cancer BEGON(IA)? For more excellent puns and the answers to these questions and more, listen on!

Another year, another international oncology conference in a beautiful European locale. In 2023, the world's oncology community has descended on the Spanish capital Madrid to discuss the latest and greatest scientific developments in Medical Oncology. And as always seems to be the case, Michael and Josh remain at home listening to this avalanche of information virtually. Despite a distinct lack of sun and Español, our intrepid duo will continue a grand tradition that dates back to 2022: bringing some of the best highlights from Madrid directly to your ears across a series of episodes to be released this week.

In the first episode of this series, Josh and Michael start in the most difficult of tumour streams: CNS oncology, an area where outcomes continue to be incredibly poor. ESMO 2023 brought some very interesting early-phase trials and no small amount of controversy, but that silver bullet unfortunately continues to elude oncology's brightest minds. Listen on to find out more.

Cisplatin is the mainstay for concurrent chemoradiotherapy in Locally Advanced Head and Neck Cancers. What happens to that significant group of patients who cannot have cisplatin? Michael and Josh focus on this challenging subgroup of patients. Can docetaxel be used as an alternative? This week, they debut a small but significant segment of our humble podcast called "Spotlight", where we dive deep into a single potentially practice-changing trial. Enjoy!

Gynaecological malignancies are a diverse group of terrible malignancies. From ovarian to endometrial to cervical, these cancers are notorious not just for their mortality burden, but the significant morbidity that they can inflict. To explore how to combat these challenging clinical entities, Michael and Josh interview Dr Vish Boolell, a clinical oncologist who brings his vast practical and trial experience to bear in exploring how to best treat patients and manage the myriad challenges gynaecological cancer can present. Today's episode is a must-listen for anyone who has been confronted by a malignant bowel obstruction, or wondered about the significance of dMMR in endometrial cancer, or who simply want some practical tips about how to best help their gynae onc patients.

It is frequently said that it takes a village to treat a patient with cancer. However, beyond the nuts and bolts of medical and allied health treatment, there exists a whole other world of advocacy and education. Charitable and not-for-profit foundations, both nationally and internationally, have done incredible work for many years in raising awareness and funding for cancer treatment and prevention, as well as providing both patient- and doctor-centred education. Oncology for the Inquisitive Mind is incredibly privileged to welcome the CEO of one such organisation, Meredith Cummins of Neuroendocrine Cancer Australia. Meredith brings decades of experience in oncology nursing, governance, fundraising and advocacy, and has done invaluable work in shining a light on the lesser-known challenges facing patients and doctors dealing with neuroendocrine cancers

"I have not failed, I've just found 10,000 ways that won't work!" so said Thomas Edison in describing his journey to the incandescent light bulb. This quote seemed appropriate as Michael and Josh conclude their journey in the neuroendocrine space and discuss neuroendocrine carcinomas (and poorly differentiated metastatic neuroendocrine tumours). Sometimes, when you are working in the oncological world, we all feel a bit like Thomas Edison, pouring sweat and tears into research that doesn't live up to expectations. But much like Thomas Edison, each step in this journey could revolutionise humanity or oncology, much like the CDK4/6 inhibitors, immunotherapy or tyrosine kinase inhibitors.

But we aren't there yet. This week, Michael discusses the immunotherapy agent (Spartalizumab) while Josh goes old-school and discusses the TOPIC-NEC Japanese trial comparing etoposide and cisplatin (EP) to irinotecan and cisplatin (IP). Michael and Josh smell small cell similarities coming aboard the neuroendocrine express!

Neuroendocrine Tumours could be described as an impassable obstacle, more complicated the more you research. That's where Michael and Josh come in, and this week, explore Grade 3 metastatic neuroendocrine tumours. Michael provides a brilliant overview of this well-differentiated cohort and the lack of efficacy platinum chemotherapies have, while Josh discusses CAPTEM (temozolomide and capecitabine) through a systematic review. Interestingly many of the current data is retrospectively collected, highlighting how challenging it is to collect enough patients to pursue meaningful research.

Note- there is a quote from Lance Armstrong, who was stripped of his titles due to illegal doping (which we do not endorse); he did start the Livestrong Foundation to support those affected by cancer.

"We go to the moon and other places not because they are easy, but because they are hard." So spoke US President John F. Kennedy, in a speech that galvanised the American public and fostered widespread support for the space race and the Apollo space program that would culminate in Neil Armstrong and Buzz Aldrin landing on the Moon on July 20, 1969. A similar approach must be taken to the treatment of neuroendocrine tumours, a rare and difficult-to-treat cancer type requiring inventiveness, preparation and lateral thinking (almost) on the level of the Apollo and Soyuz astronauts.

Last week, Michael and Josh discussed the front-line treatment of low-grade, well-differentiated neuroendocrine tumours. However, it always pays to be prepared. To that end, today our intrepid "onconauts" explore the lesser-known frontiers of later options, focussing on the competing everolimus and sunitinib. Will one option triumph over the other and reach the surface of the tumour first? Listen on to find out.

Between 1933 and 1944, Americans huddled around their radios to listen to the words of Franklin Delano Roosevelt, the 32nd President of the United States. Covering topics ranging from the 1936 recession to World War II, FDR titled these addresses "Fireside Chats", giving very high-concept topics a more personal, intimate feel. Let it never be said that Oncology for the Inquisitive Mind is above shamelessly cribbing ideas from history.

In this series, on the first Wednesday of each month, Josh and Michael will go away from their usual format of data dissection. They will instead turn their attention to a cancer-related article, film or other media and discuss it with the same convivial atmosphere of FDR. In this episode, they discuss a New York Times opinion piece from August 2023 titled "Not Everything We Call Cancer Should Be Called Cancer," trying to strike a balance between personalisation and de-escalation of management of low-risk, pre-cancerous lesions while also viewing such discussions from the perspective of patients.

Neuroendocrine tumours (commonly referred to as NETs) is the topic for this week's episode of Oncology for the Inquisitive Mind. Michael and Josh thought it could be easily covered in a single episode, but they were wrong. This is not dissimilar to the recurrent cancellation of Futurama, a television series with nine lives saved by every network in existence.

Neuroendocrine tumours are a diverse, heterogeneous, rare group of cancers that can occur throughout the body. The most common location is the gastrointestinal tract, lung, and pancreas. Of course, these aren't the only locations with NETs forming in the thymus, prostate, breast and skin. To complicate things further, the classification of NETs has changed multiple times over the past two decades.

This first episode of our four-part "tour de force" will summarise well-differentiated neuroendocrine tumours and the pivotal studies of lanreotide and PRRT (peptide receptor radionucleotide therapy) with lutetium dotatate.

Previously, on Oncology for the Inquisitive Mind, Josh and Michael discussed the common systemic therapies available for early and advanced testicular cancer: single-dose carboplatin and bleomycin + etoposide + cisplatin (BEP). However, like the beginning of any good story, this is just the beginning. All the knowledge of chemotherapy in the world is nothing without knowing how to apply it. In this episode, our hosts attempt to tackle this very topic, dissecting the when, where and why of the treatment of testicular cancer. Consider this your Hitchikers' Guide to Germ Cell Tumours.

On this, the tenth episode of OncoSnacks, Josh and Michael discuss the management of a common but no less important problem: superficial venous thrombosis and thrombophlebitis. While for the majority of cases the treatment is purely symptomatic, in a small minority of cases superficial venous thromboses can be a precursor of more serious thromboembolic events. This broad range of possible outcomes makes the management and risk stratification of apparently minor thromboses all the more important, particularly in the oncology patient population. Listen on as Josh and Michael aim to shed some light in this dark topic.

Edward Gibbon, an English historian and politician, once quipped, "History is indeed little more than the register of the crimes, follies, and misfortunes of mankind." This episode, which lacks historians and politicians, covers testicular cancer, a topic humankind has had a love-hate relationship with for millennia. As a historical concept in the Middle Ages, men who wanted to have a male as an offspring would sometimes remove their left testicles as the belief was that "boy" sperm was made in the right testicle and "girl" sperm in the left.

We don't entertain such nonsense here on Oncology for the Inquisitive Mind. Instead, we discuss testicular cancer, an uplifting episode with high cure rates and a debate regarding observation versus treatment. Will there be a future when one can perform surgery alone? Does radiotherapy have a role, and do the pros outweigh the cons of chemotherapy?

In this episode, the Nautilus reaches its final destination, where Michael and Josh pursue a deeper understanding of ROS1, and KRAS mutated lung cancer. ROS1 reflected less than 3% of non-small cell lung cancer, while KRAS is abundant and can reflect up to 25% of lung cancer patients. The challenge lies in the targets, with the only approved KRAS treatment sotorasib targeting a single KRASG12C mutation. Many, many more KRAS mutations exist in the wild. Michael uses his oxygen tank to discuss an integrated efficacy and safety analysis of entrectinib, and Josh breaks free of a shark and highlights the CodeBreaK 200 study.

In this episode, Michael and Josh step onto the oncological Nautilus, to begin their journey of 20,000 Leagues Under Lung Cancer, to examine non-small cell lung cancer with mutations other than EGFR. The first step on their journey is discussing the anaplastic lymphoma kinase, a tyrosine kinase inhibitor associated with the development of non-small cell lung cancer in younger patients who have never smoked. Thankfully, unlike their previous episode, there are treatment options galore for patients with ALKmut NSCLC. Two of the contenders for the title of "The King of the ALK" are alectinib and lorlatinib. Alectinib has more robust overall survival data, but lorlatinib has hazard ratios so ridiculously good that they would almost meet statistical significance as p values! So which is better? Listen on to find out.

There are cancers that grow slowly. There are cancers that do not grow at all. And then there are cancer's like today's subject, that are notorious not just for their ability to completely overcome a patient in a very small amount of time. Extensive-stage small cell lung cancer remains a very difficult condition to treat, highly prone to relapse and with few effective options beyond - or perhaps even including - the first line setting. While the medical and scientific community remain stalwart in their quest for therapeutic options, success stories have been few and far between. In this episode, Josh and Michael look at one success story, and one study dredged up from the pre-Internet era, to illustrate the dichotomy and discuss the challenge of treating this, the most aggressive of solid tumours.