During his days as a medical student, Prof. Oya felt that urology was a world of its own.
"I went through clinical training across various medical departments, but I was particularly struck by the comprehensiveness of urology, which handles everything from diagnosis to surgery and drug therapy. For conditions like stomach or lung cancer, typically, a patient’s diagnosis is conducted by the internal medicine department and handed off to the surgery department for operation before returning to internal medicine for drug treatment. In contrast, urology doesn't have such divisions—we see the entire spectrum of a patient's care. Not only does the urology department perform serious surgeries like kidney transplants, but it also administers advanced drug treatments, and there is also a well-structured environment for basic research and other studies. I was captivated by the fact that all of this could exist in such a small department.”
Prof. Oya says the unique atmosphere of the department also deeply resonated with him.
“It was a liberating environment, unbound by stereotypical values. Younger faculty members would openly speak their minds to their senior colleagues, embodying the Keio principle of hangaku-hankyo ('learning while teaching, teaching while learning’). Even in the 1980s, there was an unusually high number of individuals with a global perspective, and discussions about research or conferences abroad were commonplace. Above all, Professor Hiroshi Tasaki, the head of the Department of Urology at the time, was an artistic soul with a passion for painting, and his approach to medical practice and research was truly distinctive from anyone else I know. He possessed the kind of charisma that made you want to work with him.”
Prof. Oya thought that in a small department like this, he would likely receive more personalized attention. Convinced that if he worked hard, he would eventually become an expert in the field, and he had no hesitation in joining the Department of Urology.
“Choosing to study at Keio and the Department of Urology was the best decision I've made in my life so far. Mind you, I've made various other choices that didn't pan out so well.”
After joining the Department of Urology, Prof. Oya pursued further studies at New York Medical College and the University of Düsseldorf. He then returned to Keio University's Department of Urology in 1998. After building his career as a leading figure in cancer research, he was appointed the sixth head of the Urology Department in 2007. With the fervent belief that if something is worth doing, it's worth doing wholeheartedly, he aimed to transform the department into the best urology department in the world. From the outset of his appointment, Prof. Oya proposed and championed a unique vision for urology, which he systematized as the “1+3 Structure.”
The “1” in “1+3” represents malignant diseases. This encompasses the three major urological cancers: kidney, bladder, and prostate, as well as testicular cancer, adrenal cancer, and retroperitoneal tumors. The “3” in “1+3” consolidates a wide range of benign diseases into three distinct domains. “Domain I” focuses on nephrology and dialysis medicine, which also includes kidney transplants. “Domain II” is centered on endocrine-metabolism and neuro-urology, managing conditions such as adrenal disorders, enlarged prostate, neurogenic bladder, and urinary functional disorders. Lastly, “Domain III” delves into reproductive medicine and andrology, addressing male infertility and sexual dysfunction.
"For instance, surgeries for prostate cancer often lead to complications like urinary disorders or erectile dysfunction. However, there are many hospitals that, while capable of performing cancer surgeries themselves, are ill-equipped to address these benign conditions. At Keio, our structured approach spans diverse domains, so we can handle any complications that might arise in the three domains (“3”) after cancer surgery to address a malignant disease (“1”). If a urinary disorder arises, an expert from Domain II can handle it. If symptoms of ED are observed, a specialist from Domain III can step in. While there are more than 80 university hospitals in Japan, only Keio offers comprehensive care that encompasses nearly all urological conditions.”
Moreover, in 2009, Prof. Oya established a specialized pediatric urology team, one of only a few in the field. This has enabled the department to address a range of pediatric diseases, such as congenital hydronephrosis, vesicoureteral reflux, hypospadias, and undescended testes, and they now perform over 150 surgeries annually. “We’ve seen surgical techniques from pediatric urology applied to adult treatments, and they also offer early-career physicians the chance to acquire reconstructive surgery skills.”
The “1+3 Structure” covers a wide range of urological diseases and leads to organic collaboration between each domain. Prof. Oya emphasizes the fact that this comprehensive scope leads to high-quality medical care, research, and education.
“Urology may seem like a small department, and it may appear narrow in scope, but once you step inside, the world that unfolds is surprisingly profound and exhilarating. I’ve always thought of it as similar to Alice in Wonderland in that regard.”
Prof. Oya has dedicated 36 years to the field of urology and says that when he first became a doctor, he never imagined the dramatic transformation that urological treatments would undergo. Indeed, over the past two decades, there have been numerous paradigm shifts in the treatment of urological diseases.
One notable example is robotic surgery. In 2012, robot-assisted laparoscopic radical prostatectomy became the first such operation covered by insurance in Japan. Following this, many other surgical procedures were added to the list, including adrenalectomy, partial nephrectomy, radical cystectomy, pyeloplasty, and sacrocolpopexy.
“Robotic surgery offers numerous advantages, such as enabling more delicate and accurate surgical manipulations, drastically reducing blood loss, leaving smaller and less noticeable incisions, and promoting quicker post-operative recovery. Today, almost all surgeries for prostate cancer are performed using robotic assistance, with kidney and bladder cancers predominantly treated by either laparoscopic or robotic-assisted surgeries. Since 2018, robotic surgery has gradually expanded into other surgical fields, but there is no doubt that the field of urology was the driving force behind its technological advancement.”
The standard of care in pharmacotherapy has also been evolving rapidly. “Take kidney cancer, for example. The previously dominant treatment was cytokine therapy, which involves administering proteins produced by immune cells, such as interferons and interleukins, to activate the function of these immune cells and target cancer cells. Although this was a groundbreaking therapy at the time, its success rate was relatively low at around 15%.”
Things took a significant leap forward in 2008.
“The introduction of molecular-targeted therapies focusing on tumor angiogenesis drastically improved patient outcomes. These therapies suppress tumor growth by inhibiting intracellular signaling pathways involved in the proliferation of tumor cells and vascular endothelial cells using tyrosine kinase and mTOR inhibitors. I recall administering sunitinib, an anti-cancer medication that had been recently approved, to a patient who had just been urgently admitted. Fifteen years on, that patient is still alive. Such an outcome would have been unlikely if we had still been administering a drug like interferon alfa.”
Then, in 2016, immune checkpoint inhibitors, which block the mechanisms cancer cells use to evade the immune system, were approved for insurance coverage. Their effects have been shown to last for extended periods after administration, broadening the range of therapeutic options available.
Then came 2018. Urological treatments witnessed a transformative shift with the introduction of combination immunotherapy, which was so groundbreaking that it was heralded as the dawn of a new era.
“Combination immunotherapy involves administering a combination of two immune checkpoint inhibitors (PD-1/PD-L1 inhibitors and CTLA-4 inhibitors) or a combination of molecular-targeted drugs (VEGF inhibitors) and immune checkpoint inhibitors (PD-1/PD-L1 inhibitors). Currently, we have five combinations at our disposal, allowing us to tailor the treatment based on the patient’s condition and preferences.”
Compared to using only molecular-targeted therapies, combination immunotherapy has shown remarkable outcomes. Data indicates that the 18-month survival rate has increased to approximately 1.5 times for those with intermediate prognoses and 2 to 3 times for those with poor prognoses.
“The advancements we've seen have already surpassed our expectations. As we speak, clinical trials are underway worldwide to uncover even more potent combinations.”
Thanks to advances in surgical treatments and drug therapies, there have been significant improvements in outcomes for urological diseases. Nevertheless, Prof. Oya emphasizes that the number of people dying from urological cancers hasn't reached zero, and there are still numerous unmet medical needs and challenges to overcome.
One formidable challenge is how to address drug resistance in cancer—those that either don't respond to treatments or when efficacy diminishes over time.
“For instance, even though the success rate of combination immunotherapy for kidney cancer is currently high for many patients, there will inevitably come a time when its efficacy wanes. Cancer cells are cunning adversaries, adept at morphing and adapting in order to survive. Research to elucidate the mechanisms behind this drug resistance, and to seek out new treatment methods, is underway both domestically and internationally.”
Take prostate cancer, for example. As treatment progresses, some cases of castration-resistant prostate cancer may mutate into a more challenging form known as neuroendocrine prostate cancer, characterized by small-cell prostate cancer-like traits. Researchers have found mutations in the tumor-suppressor genes p53 and pRB in this type of cancer.
“We noted that the progression of this cancer's stem cell-like characteristics and its resistance to treatment was similar to the process of acquiring pluripotent stem cells from somatic cells (induction of iPS cells). We discovered that a group of cells with a high expression of OCT4, one of the Yamanaka factors, were becoming more resistant to chemotherapy, and in 2015, we became the first in the world to successfully move to clinical trials by identifying drugs that were effective when combined with existing chemotherapy. For almost a decade, we've been dedicated to our research into reprogramming therapy—a method of making cancers once again sensitive to chemotherapy, even after they've grown resistant. We intend to diligently continue our research and pave the way for new treatments.”
The treatment of bladder cancer also presents its own challenges.
“Bladder cancer treatments include transurethral resection of bladder tumor (TURBT) and intravesical therapy, where BCG (Bacillus Calmette-Guérin) is administered directly into the bladder. However, bladder cancer tends to develop multifocally in multiple areas and is characterized by frequent recurrences. Once the cancer invades the muscle layer, a complete bladder removal is typically required. This invasive procedure, which also alters one's appearance, is something most would prefer to avoid. Thus, we continue our research to find treatments for non-muscle-invasive bladder cancers that are resistant to BCG.”
“My team and I are determined to address unmet medical needs without settling for the status quo. I believe our collective dedication in this regard will be the driving force behind advancements in urology.”
Despite his busy life as a doctor, researcher, and educator, Prof. Oya always believes in trying his best to engage wholeheartedly with the person in front of him.
“Whenever I see patients in the outpatient clinic, I always pay close attention to their expressions as they leave the examination room. If they seem unsatisfied, I ask them, ‘If it's alright, shall we set aside more time later?’ When a doctor does everything they can and genuinely engages in the conversation, the patient will feel understood and satisfied, no matter how difficult the situation may be. Medicine and medical care as a whole are deeply rooted in humanism, so it is crucial for a doctor to always empathize with their patient, considering their background and personality when communicating with them. There's no such thing as being too considerate toward a patient. This is actually something I've learned here at Keio from observing the exemplary behavior of my colleagues at the Department of Urology. I hope younger physicians can also glean something from watching how I approach my work.”
Prof. Oya's motto is the same, whether giving a university lecture or at an academic conference.
“I teach a class for new first-year students called ‘Introduction to Medicine.’ I kick off the first lesson with, 'Thank you for being here today! Now let's get into it and do this thing!’ This gets the entire classroom buzzing and is usually met with cheers from the students. After class, students often come up to me to say how much they enjoyed it. Even at academic conferences, the moment I step up to the podium, I start by making eye contact with the audience. If they're intrigued, thinking, 'Who is this guy,’ then I consider that a win. Whether it's teaching or giving a lecture, if you approach it half-heartedly, your message won't resonate. The key is to come thoroughly prepared and to give your all for the benefit of those in front of you. I believe that's what matters most.”
In Japan, urology is often perceived as one of the lesser-known medical specialties. However, it's quite the opposite abroad. Urology enjoys immense popularity and is regarded as one of the more elite and competitive fields to enter.
“Prof. Katsuto Shinohara, who has made significant contributions at the University of California, San Francisco (UCSF) Department of Urology, once mentioned that their urology program has just three spots for around 300 applications they receive a year. Urology was just as popular at the University of Düsseldorf in Germany, where I studied. There, you had to get involved with the department as a student; otherwise, it was nearly impossible to secure a position.”
We asked Prof. Oya to break down why urology garners such admiration.
“I think what makes the job so rewarding and interesting has to do with being responsible for everything from diagnosis to drug treatment, surgery, and even post-operative holistic management. The weight of the responsibility we carry as doctors is immense, and the satisfaction derived is unparalleled. Urological conditions also require fewer emergency surgeries, and post-operative complications are rarer, which helps us maintain our quality of life. In fact, there have been studies indicating that urology has one of the lowest attrition rates among medical specialties. So once you're in, very few leave. On a side note, we currently have promotional posters for the urology department here on campus that say, 'Even if we could do it all over again, we'd still be urologists.' I really think that hits the nail on the head.”
Prof. Oya chuckles as he comments that people in Japan are now slowly starting to catch on to the incredible world of urology.
“This year, we welcomed seven new members to our department. Urology is far ahead of other specialties when it comes to robotic surgery, which attracts all of those people wanting to become experts in this cutting-edge technology. We see a lot of people who are eager to try something different, something beyond the conventional divide between internal medicine and surgery. Contrary to what some might think, it's not uncommon to find female doctors in this field either.”
Prof. Oya and his team are deeply passionate about nurturing the next generation of physicians.
“For the future of urological medicine, we need these young physicians to not only follow in our footsteps but to surpass us. That's why we emphasize equal opportunity and the importance of always challenging and learning from each other. And I often tell them not to face tough situations alone. Those moments when you're feeling down, or you think you’ve hit rock bottom—those are the moments you need to experience with your peers and rise above them together.”
“Good horses are common, but good riders are rare— this old Chinese proverb is a metaphorical way of saying that you can always find individuals with potential or talent, but finding someone who can effectively recognize, nurture, and utilize that potential is much rarer. Even with talent, without a guiding hand, one can’t become a great doctor. I'm proud to say that the environment at Keio offers the perfect foundations for becoming a doctor. I hope that the young people who choose the Keio University Department of Urology will find inspiring mentors here, flourish under their guidance, and embark on a rich and rewarding journey as medical professionals.”
Mototsugu Oya graduated from the Keio University School of Medicine in 1987 before pursuing further studies in urology at New York Medical College in 1995. In 1997, he continued his urological training at the University of Düsseldorf. Returning to Keio in 1998, he took up a position as an assistant in the Department of Urology at the university’s School of Medicine. In 2004, he was appointed as a Senior Scientific Research Specialist in the Research Promotion Bureau of the Ministry of Education, Culture, Sports, Science and Technology (a role he held concurrently until 2006). Since 2007, he has served as a professor in the Department of Urology and was appointed Vice Director of the Keio University Hospital in 2013. His accolades include the 12th Japanese Urological Association Award and the 6th Organon Research Grant in Urology , among numerous others. Prof. Oya is also set to preside as the congress chairman of the 61st Annual Meeting of the Japan Society of Clinical Oncology, held in October 2023.