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This year, the Society of Urologic Oncology awarded Curtis A. Pettaway, MD, the Huggins Medal for achievement and contributions in the field of urology. In an interview with Urology Times, he reflects on what innovations and research led up to this point. Pettaway is a professor of urology at the University of Texas MD Anderson Cancer Center in Houston.
I took a while to reflect on it. And of course, at first, you're shocked and humbled that you get this recognition. When you look at the broad context, I realized I needed to think a little bit more deeply about how I got to where I'm at. Also, from the standpoint of looking at those who came before me, and one of the things I wanted to bring out in the Huggins Medal Lecture, was the fact that R. Frank Jones was a urologist who was the first Black board-certified urologist back in 1936.1 This was at a time when Blacks were denied training in subspecialties, so this was quite an achievement for him and kudos to the American Urological Association for certifying him back in 1936. And so, when I look at somebody like this who, during his career, trained 80% of the practicing Black urologists, that was a tremendous feat. And I hate to be cliche, but I do stand on the shoulders of somebody like that. I'm here today because of people like that who went before me. And so, it was very touching to be able to bring that out and to let others know that because of people like that who stood and endured many unimaginable trials, we as the next generation of Black urologists are able to then come into the field, are able to make discoveries, are able to move the field forward, and are able to be recognized as I was. So, I was humbled for many different things. I believe that this is, of course, a harbinger of what is to come—those of underserved backgrounds given opportunities and being featured in our organizations.
When I look at it, my career path has been one of studying the biology of prostate cancer, specifically where it relates to advanced disease and especially among African American men who have a higher incidence and mortality from the disease. I was very proud of a couple of things. I was a part of one of the largest African American hereditary prostate cancer projects funded through the National Cancer Institute, led by my mentor Isaac Powell, MD.2 I was really privileged to be a co-investigator on that study.
One of the other areas of interest to me is rare cancers. And the area that people probably are most familiar with my work is in the area of penile cancer. When I look at a disease like penile cancer, it's a rare cancer. It's an orphan disease, and there's not a lot of research funding to study it likely because it is so rare. Most urologists see maybe 1 case per year. However, if you practice at a tertiary referral center, like at MD Anderson Cancer Center, we see about 50 cases per year. The dilemmas in dealing with penile cancer surround the management of the inguinal lymph nodes. The situation with penile cancer is that in patients that have inguinal lymph node disease, if you diagnose the disease earlier and treat them, they can live a long time. The problem with earlier diagnosis is that it generally requires surgery to find the disease. You have to remove the involved lymph nodes. Now, the problem is that the procedure itself is morbid. And so, we had a dilemma where among all patients would potentially expose a lot of patients who didn't need it to excess morbidity and side effects, whereas if you waited too long, you wouldn't really be able to cure them of the disease that was growing occultly.
My 2 research focuses in penile cancer were to try to develop strategies that would help decrease the morbidity of the disease, and to develop new treatments for more advanced disease. And so, from the standpoint of developing and promoting strategies or discovery to decrease morbidity, the first thing that we did is we looked at who was selecting for the inguinal dissection. In other words, who would be most at risk? We explored pathologic factors, such as grade of cancer, lymphovascular invasion, and tumor stage. We put those factors together and developed risk groups. Others had done some similar work in that area as well. Selection of more higher-risk patients for the inguinal lymph node dissection allowed us to avoid complications among lower risk patients.3
Secondly, what we began to do is try to develop templates of surgery that would minimize the amount or the number of nodes taken. We decreased the size of the inguinal nodal field, from what was considered a 'traditional radical dissection field' down to one that was a smaller field but still was able to accurately stage patients. That was called 'superficial dissection.'4
The other thing we did was to capitalize on existing technology. We performed one of the first phase 1 studies, evaluating the safety and feasibility of robotic assisted inguinal lymph node dissection, [or] RAIL.5 What we did in that study was to perform a robotic dissection in men who had high-risk features in the primary tumor. after we performed the RAIL, one of my partners who wasn't involved in the study would make a small incision and actually look at the field and make sure that we did a complete dissection. We found that our lymph node yields from the robotic dissection were excellent, and we found that the dissections were complete in almost every case. This formed the rationale for minimally invasive staging of penile cancer which we hope will limit complications.
Now, on the advanced side, I worked with one of our medical oncologists at the time, Lance Pagliaro, MD, and he evaluated the existing systemic regimens to treat advanced metastatic disease. We noted that some were toxic and the of chemotherapy to shrink tumors was mediocre. Lance also looked at the head and neck literature. Dr. Pagliaro selected one of the regimens from the head and neck literature, which is called cisplatin paclitaxel ifosfamide. We call it 'TIP' these days. We did a preliminary study and found that a number of patients after treatment had no more disease.2 So, we did what's called a 'phase 2' study, where we evaluated the effect of this treatment on a sequential group of patients, and we found that response rates in that group were about 50%. These were men with advanced disease, many of whom became operable after cytoreduction with chemotherapy.6 The TIP regimen was published about 10 years ago and is one of the front-line regimens that's used today in treating penile cancer patients. And I'm one of the principal investigators for an international penile cancer trial called InPACT, which stands for The International Penile Advanced Cancer Trial.7 We're actually using the TIP regimen in this trial, so it was really gratifying to see some of your early work evolve, and grow into a large international study.
In terms of looking at your career, especially in urologic oncology, it's important to listen to your patients and develop questions that really are relevant to your areas of interest and areas that will advance our knowledge in treating patients. If you do that, then what you want to do is you want to read, you want to become the expert in that area, know what is known, know what is not known, [so] you can formulate your research questions. The next thing I would say is get a mentor, get someone who's gone before you and has made significant advances in the field. They've overcome challenges, [and] they probably have been able to achieve funding [and] develop all types of resources to answer questions. And so, they can shorten your learning curve and help you overcome some of the challenges that will surely come if you're going to advance in the field, and [also] answer your specific question. I think that, again, formulating the question, reading, mentorship, all those things are really important.
First of all, the area of medicine is huge. And if you're thinking about urology, then what I would do is get exposure as early as possible—hang around the urologists at your institution, see what they do, ask yourself whether this is interesting to you. Also check out some of the other surgical subspecialties and medicine subspecialties to make sure that you're more of a “surgical type” versus a “medical type”. Once you decide that you really like the surgical experience, then it's a good idea to check out some of the other surgical subspecialties to make sure you really do want to do urology. And then, if you decide, "Okay, I really want to do urology," I would get some exposure and hang around some of the urology staff at your institution, talk to them, get their advice, and see if they have any interesting research projects that they need some help with. This will allow you to gain more experience and knowledge and really become knowledgeable about a subject. Furthermore, if you do a good job, you'll also have a source for a good recommendation by working with that staff member.
References
1. Downs, TM, Rayford W, Davis DE, Nakada SY (2014). Richard Francis Jones--opening doors and diversifying the urologic workforce: a pioneer in the training of African urologic surgeons in North America. Urology. Vol. 83, pp. 1213–1216). Doi:10.1016/j.urology.2014.01.035
2. Powell IJ, Carpten J, Dunston G, et al. African-American Heredity Prostate Cancer Study: A Model for Genetic Research. J Natl Med Assoc. 93(4):120-3, 4/2001. PMCID: PMC2593987
3. Slaton JW, Morgenstern N, Levy DA, et al. Tumor stage, vascular invasion and the percentage of poorly differentiated cancer: independent prognosticators for inguinal lymph node metastasis in penile squamous cancer. J Urol. 165(4):1138-42, 4/2001. PMID: 11257655
4. Bevan-Thomas R, Slaton JW, Pettaway CA. Contemporary morbidity from lymphadenectomy for penile squamous cell carcinoma: the M.D. Anderson Cancer Center Experience. J Urol. 167(4):1638-42, 4/2002. PMID: 11912379
5. Matin SF, Cormier JN, Ward JF, et al. Phase 1 prospective evaluation of the oncological adequacy of robotic assisted video-endoscopic inguinal lymphadenectomy in patients with penile carcinoma. BJU Int. 111(7):1068-74, 6/2013. PMCID: PMC3651805
6. Pagliaro LC, Williams DL, Daliani D, et al. Neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy for metastatic penile cancer: a phase II study. J Clin Oncol. 28(24):3851-7, 8/2010. PMCID: PMC2940402
7. Canter DJ, Nicholson S, Watkin N, Hall E, Pettaway C, InPACT Executive Committee. The International Penile Advanced Cancer Trial (InPACT): Rationale and Current Status. Eur Urol Focus. Published May 2019. e-Pub May 2019.