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Cirurgia em Urologia Oncologica XV Workshop de Urologia Oncologica J.Edson Pontes KCI/WSU “Surgery is like a Savage, who attempts to get by force, that which a civilized men would get by stratagem.” John Hunter (1728-1793) Surgical Oncology is Changing 1960’s - 80’s – Super Radical Surgery ICU care, blood banking, anesthesia techniques 1990’s – Pendulum begins to swing back Minimally invasive surgery 2000’s – Less is more Recognition that surgery is only one player Better radiotherapy and better chemotherapy Technology is the engine of change Super Radical Surgery 1960s—1980s • Could it be done • Often without regard to quality of life or function Sentinel Lymph Node Biopsy Standard of Care a) Melanoma b) Breast c) Penile cancer Colon, rectum, gastric, head & neck, thyroid, gyn, urologic Renal Cell Carcinoma • Early 60s- radical nephrectomy for most renal masses. 30% were benign. • During the 80s-CT scan, early MRI- Better definition of masses. Radical nephrectomy mostly for cancer. • During the 90s- RSS for small peripheral tumors. • In the last decade: RSS gold standard, Laparoscopy, Cryosurgery, HIFU. Testicular Cancer • Bilateral RPLND in all patients with NSTT. • Modified RPLND. • Neo adjuvant chemotherapy for RP nodes, followed by surgery only when residual masses were present. • Surveillance for stage I Penile Cancer • Better identification of sentinel node with dyes and radioactive pharmaceuticals. • Avoidance of Inguinal L.N. dissection and its complications. Surgical oncologist is one player on a multi-modal team Traditional Oncologic Approaches • Phase I : determine toxicity following animal studies. • Phase II: Activity against certain tumors. • Phase III: comparative studies against established treatments. Problem with large group trials now • Many trials are begun asking questions rendered • • obsolete by changes in therapy over the life of the trial Modern technology, informatics, and therapeutic interventions are changing too rapidly to sit still for a clinical trial Technology and MIS make many randomized trials impossible eg. TCCAA vs. CABG or local excision of rectal cancer vs.APR Benefits of large Phase III studies . • Among the curable malignancies in GU Cancers • i.e. Wilms and Testicular Germ cell tumors, no randomized trials were needed. Large prospective randomized trials for Prostate and Bladder cancer produced improvements measured in months. Statistically significant but clinically irrelevant! Skill Set for Modern Surgery • Minimally Invasive Surgery Techniques MIS, NOTES, TEM, IGS • High resolution ultrasound • CT scan in O.R. – skill sets for the modern surgeon Advanced Surgical Technology & Innovation Initiative (ASTII) • Cooperation with the SSIM lab School of Engineering • Collaboration of surgeons and engineers to develop novel tools for clinical use • Presently seeking funding • Founding member of iSURGTEC– Un of Madrid, Un of Chicago, UCSF- surgical Depts with interest in technology 20th century 21st century 2D slices 3D virtual patient New vision of the patient Da Vinci Robot The Era of new technology brings New Challenges! Era of the prospective randomized study • 70s,80s,90s and now--Phase III trials these trials would come to form what we now call Level I evidence well regulated (IRB), oversight QUESTION How do we introduce new ideas, new therapies and new technology, in a time when conventional scientific means of assessment cannot keep up with the explosion of knowledge and technology? • Technology and therapeutic innovation is occurring more rapidly than can be assessed by conventional means Surgical research esp. cancer research is at a tipping point Dilemma: How to introduce and use innovation yet respect and protect the rights and well being of our patients? How can we be cautious and forward thinking at the same time? Can we be both scientific and non-linear at the same time? Hard thing to acknowledge • Unscientific • Anti-intellectual • Dangerous What should we do? (I) • Delay innovation and new technology • Develop new paradigms for vetting progress • We must use technology to overcome the obstacles created by technology Surgical procedures have always carried with them the elements of innovation Ethics Just as unethical to consign a patient to treatment which is obsolete as to assign a patient to treatment which is untested Future • Develop registries to keep tract of what we do and outcomes • Usefully crafted Electronic Medical Records accessible to data acquisition Future • Computer modeling, planning and simulation will inform our actions and protect our patients What should we do? (II) • I have cured many cancer in mice! • Human diversity is such, that treatment • applicable to inbread animals with uniform tumors( cell lines), do not work in humans. With advances in pathology, tumors can be individualized at the molecular/genetic level to select treatment. Future Custom therapy is on the way molecular and genetic markers in the tumor molecular and genetic markers in the host, invitro assays Targeted Therapy Evolution in sequencing the Human Genome • With a budget of > $3 Billion, thousands of • • scientists it took more than a decade to map the human genome. Today it is possible to sequence the human genome in about 8 days, at a cost of $10 thousand. The possible use of “nanopore sequencing” could bring the time down to minutes or hours at a cost of <$1 thousand. These are the most exciting of times We must ask ourselves how we will evaluate risks/benefits and outcomes for the individual patient with the same scientific vigor that we have venerated the prospective randomized trial New Paradigm for the Future • Based on individual uniqueness and customization • Based on computer modeling and predictive simulation • Based on solid well developed ethical principles Fundamental to the Discussion • Can nonempirical constructions lead to genuine knowledge in science? • Can “thought experiments”, or computer modeling have a scientific end in themselves or are they only to be justified as stages on the way to genuine empirical discovery Conclusions Trend in surgical oncology: Less is More Seen in Minimally invasive surgery Selective nodal sampling-S.L.N. biopsy Ablation methods Better imaging and guidance Organ preservation New technology Intuitive embracing of these concepts by patients circumvents Evidence Based Practice Conclusions • We live in a time when new ideas will occur at a rate • • • • more rapid than they can be systematically tested”leapfrog” It is not ethically superior to withhold potential innovations any more than it is to recklessly implement them Population statistics will have less importance as “custom” therapies, and computer modeling are developed We must rethink, restudy, redefine the ethical principles/boundaries which will guide our use of new ideas Technology must be used to overcome obstacles caused by technology Conclusions • Surgeons are in the best possible position to wrestle with • • • these issues since “the operation” has always had the elements of customization, use of innovative ideas, and need for ethical decisions Science as it is presently defined must be broadened to include carefully considered non-empirical constructionsethically bounded Some will call this thinking reckless, unscientific and dangerous Failure to do this will result in fewer innovations and stall opportunities for true breakthroughs