The Uromigos Episode 123: Legends in GU Cancer Series—Maha Hussain

Dr. Maha Hussain discusses her career in genitourinary cancer with a focus on prostate cancer.

Episode Transcript

Brian:
All right. Welcome, everyone, to the next Uromigos Legends podcast. We’re here with Maha Hussain from Northwestern today. Maha, I’m going to let you introduce yourself and use whatever titles you want in a second, but just for the audience, this is a small series that Tom and I are doing with really some of the luminaries in the field of GU oncology, to try and get really historical perspective in a given disease, and where we’ve been, some of the great successes and challenges along the way.

So, Maha, thanks for joining us. If you want to just briefly introduce yourself first, and then we’ll sort of launch into some questions for you.

Maha Hussain:
Sure. Thank you both for the opportunity and the invitation. So, my name is Maha Hussain, and I am a medical oncologist with a GU medical oncology focus. I am also the Genevieve Teuton Professor of Medicine, in the Department of Medicine, in the Division of Hem Onc, at the Lurie Cancer Center, Northwestern University.

Brian:
Thanks, and so, Maha, let’s start with how you got your start in GU oncology and really some of the early successes and challenges. I don’t know if you’ve always done GU. A lot of the folks we’ve talked with so far … You start out doing other things. You sort of find your way into GU. What was your initial path?

Maha Hussain:
I think it was something along those lines. When I started my career was actually around residency time, where prostate cancer and GU cancers were essentially huge areas of unmet need. Nobody wanted to invest in research in those areas, and similarly, head and neck cancer was the same story, and so where I trained, there was a lot of strengths in the institution at Wayne State in these areas in terms of clinical research, and so I kind of got fascinated by it, and then as I moved into my career, while I went to fellowship.

I was being groomed to be a breast cancer oncologist, but at the same time, I’m a foreign grad, born and raised in Iraq, and came in on a J visa, and so one of the areas to be in was the veteran’s hospital, where I was recruited to be in the VA, and there you saw loads of GU cancers, and the sad part was the prostate cancer patients, when we identified them, was basically emergency room coming in with a cord compression, and biopsy done, and lo and behold it’s metastatic prostate cancer.

So, it was clearly an area of unmet need, and that’s where, really, I got fascinated by it. Same thing goes with bladder cancer.

Again, this was sort of the emerging era of chemotherapy in bladder cancer, but it’s still, as you know very well, it’s an area that was really quite tough, and then of course, moving into renal cell, it was the interferon and high-dose interleukin, and there wasn’t much to do at the time, and so it seemed like an area of unmet need, and I actually got very fascinated by it, and I would say by default, as I worked in the field, by the bulk of the patients I interacted with, especially being veterans, were males, and actually we developed a wonderful doctor patient, at the human level, relationship, and then came up with ideas, grew through SWOG, and the rest is history.

Brian:
And so just to pick up on that theme, and we talked about this before we started recording, did you find it challenging? I think you were probably one of the only women at the time in GU oncology, and especially at a VA, which is a predominantly male population. Talk a little bit about those challenges.

Maha Hussain:
Well, I would say what I found at the patient level, men were more open to tell me about how they feel, as opposed to a male physician. So, they would mention things to me that they would not mention to the urologist, and you can imagine what these things could be, and so from that perspective, I think it was really very rewarding, because you sign up, and you have the oath for medicine, and you’re taking care of people, and you’re taking care of human beings.

So, the gender is a factor, but that’s not the only … It’s the human being you’re dealing with. So, in terms of the interaction, I have to say, despite the fact that I have a funky name, Arab name, it’s a name that was associated, in the beginning, with King Hussein of Jordan, and of course I’m not related to the royalty, but …

Tom:
In some respects, you are, Maha.

Maha Hussain:
Well actually …

Tom:
To us. To Brian and myself, you are.

Maha Hussain:
I think I was like, “Do you think a princess will come and work in the VA in Detroit? I don’t.”

Brian:
Good point.

Maha Hussain:
Exactly. But the other part then was Saddam Hussein, and it was like every time it’s like, “No, guys, I’m not related. It’s just a name.” So, but I have to say, I don’t feel that what I looked like, or how my accent was, or how my name was, actually was a hurdle or a barrier, to be honest with you, and I …

Tom:
Maha. Can I ask a question, Maha?

Maha Hussain:
Absolutely.

Tom:
What do you think, from an academic perspective, do you think that there were challenges around being female previously, in terms of being able to lead things, and do you think some of those challenges still exist?

Maha Hussain:
Honestly, I think there is a cultural issue, but I personally never stood up and came up with an idea and said, “Because I’m a woman, you got to give me this.” It was more of the science, the medical need, all of these things, and not viewing the male-female kind of gender issue.

I must say that I have personally not felt that I was discriminated because of that, and I will say that my mentors, and those who actually had my back, I call it, was predominantly men in the field, and I got to give credit to people like Larry Baker, who was our division chief when I was a fellow, and subsequently to that, with his support and mentorship, and whatever activities that I wanted, I go to him with an idea, and they would help facilitate.

David Crawford, the chair of the GU committee at the time, who was an incredible support, and as I said, I don’t know whether it was different times, but I don’t feel that I had … And again, it’s what I perceive. It may be different. I also think that when I entered the field, the two people were …

I should say three ladies ahead of me, slightly, not too much, slightly. One is Nancy Dawson, who was a military physician, as you know, and I met her through SWOG. The other person is Tia Higano, and you know her very well from UW, and the third person actually was in Italy at the time, was Cora Sternberg, and this was it, and so, yes, when we went to national meetings …

I shouldn’t say national, maybe GU focused meetings, no one would expect one of us to be the doctor. We must be research nurses, drug reps, something like that, but then once it opened up, it was like not an issue at all.

Tom:
They think the same about Brian now, actually. So, Maha, well, I guess we want to talk about some of your brilliant … I looked on PubMed and went through your CV, and I guess that there have been some really big moments in your career. There have been some very prominent New England Journal publications, and I guess those are the big firework displays that everyone knows about. What were the really big achievements, that you think in your career, that perhaps aren’t as well broadcast?

Maha Hussain:
Well, honestly, I think whatever that is of value is already there on the radar screen. One of the, obviously, biggest steps I would say in the field is what opened up the door for more investment and research in prostate cancer, which really the trials that led to the Taxotere or the docetaxel approval by the FDA, and one of the trials was led by Dan Petrylak, and this was at a time where I was involved in the sort of the design of the study. I was the advanced prostate cancer subcommittee chair, and we pushed for these types of trials.

The whole era of intermittent versus continuous therapy, and this was really a huge … the largest trial I’ve ever done, and I am not aware of any 3000-patient trial that’s actually an NCI sponsored type trials.

That was something that we pushed hard to do, and that happened. Moving forward, we did probably one of the largest studies for adjuvant therapy in prostate cancer. If you think about it, of all the diseases that we have, the one space where we do not have data for adjuvant therapy is really high-risk prostate cancer, post radical prostatectomy, and the cooperative groups were really amazing in that regard, with the adjuvant radiation, the trial that I designed, which was accrued and published. So, I would say these are landmarks.

Not everything was positive, but I would go back and then say … The biggest things I would say is areas where we showed an impact that led to changing standards of care, so that’s beginning with the Taxotere trials, moving into the enzalutamide in the non-metastatic castration-resistant space, moving into the lab group in the context of, again, BRACA preselected, BRACA like preselected patient population. So, these are very rewarding, I would say, experiences.

Tom:
Was there something that happened that you look back on, and think, “And that was a mistake, or I should have done that differently, or that was an opportunity missed”? Was there a drug out there, or was there a biomarker, or was there a trial that should have worked that didn’t was? Was there something that you look back on and think, “You know what, that was an opportunity that passed us by”?

Maha Hussain:
Honestly, I’m not going to say I’m perfect, but I don’t think there was. I would say that anything that we pushed for, and were part of, materialized, and again, there are times where you have ideas, but you can’t convince people to do them, and it is what it is.

But I would say, in the big picture … And one area that I forgot to mention is obviously the charted trial, the docetaxel in the adjuvant … I’m sorry, in the metastatic hormone-sensitive space. So, I think there were a lot of things that we did that I think we pushed for, and I don’t really think that there was, in retrospect, huge gap areas where I thought, “Oh my God. We have to do this,” and it didn’t happen.

I don’t think there was something like that.

Tom:
My career has made up for that, don’t worry about that, by …

Brian:
Talk a little more … A lot of your contributions and successes have been, as you mentioned, through the cooperative groups, and it seems like in prostate cancer, the cooperative groups have had an especially prominent role, maybe relative to other cancers. It’s sort of my opinion. Do you talk about that a little bit, and do you think the current role of cooperative groups is the same? They’ve obviously changed and realigned over time, but are they as well positioned to make those contributions today?

Maha Hussain:
So, I think the main issue with the cooperative groups was at two levels. One of them is the talent and the team that is there, that would help you accrue the studies that otherwise would never happen. Again, you can imagine, from a practicality perspective, an adjuvant trial in prostate cancer that could take 15 years to get follow ups, is not going to happen in a pharma setting when there’s a specific drug being tested, with an overall survival endpoint, so there could be other intermediate endpoints.

But I would say the other part was the sources of the drug, and I don’t know, gentlemen, you are relatively a bit younger than I am, so at the time that I kind of was getting into the field, the major source of agents was actually the CTA, was the NCI, and so we could get access to drugs, or do ideas that we couldn’t get funding from another source for, through that mechanism, and so I think that’s a critical part, and I still think the cooperative groups today.

When it comes to issues of new drug discovery and testing, I think that shifted somewhat, the balance has shifted, but I still think that through the CTA mechanism, there is opportunities to evaluate agents that otherwise might not be a high focus in sort of the private sector type thing, and, clearly, newer ideas that requires long term follow up and such, clearly, to me, the cooperative groups are very critical in that regard.

Tom:
Maha, what do the pharmaceutical industry do well, and what areas do we need to focus on and improve?

Maha Hussain:
Well, I think the drug discovery component, clearly, that is pretty much in the sort of the pharma space, again, there. I would say the resources, the dollars, or the pounds, or the euros, is within the pharmaceutical companies, and so if you think about all of the sort of novel agents, or agents that have had value in, say, disease settings where a sort of a public entity had tested, moving it in certain spaces, in prostate cancer, or bladder, for that matter, has been really pharmaceutical trials.

So, if you think about just the most recent ones, enzalutamide, and all of the spectrum of the non-metastatic castration-resistant space, or even the original trials for the castration resistant space, the abiraterone story, the Olaparib, rucaparib, all of these, the PARP inhibitors.

So, I do think that somehow creating a balance …

Because I’ll tell you, there is a lot of areas where there is the need for clinical benefit, demonstration or evaluation, that may not be something that could deliver tomorrow, and so the question comes up, is that not a question worth answering, and this is, to me, where the co cooperative groups and or sort of the public entities, I call it, ERTC, things like that, needs to kind of be involved in.

The reality of it is money doesn’t grow on trees, and there is prioritization that’s needing. When all is said and done, I would say, right now, the biggest investment is in newer agents. At the end of the day, we’re not curing advanced cancer, and so …

Tom:
Have you seen …

Brian:
I have a question maybe building on that. Have we maxed out hormonal manipulation in advanced prostate cancer? I mean, with androgen annihilation, as they call it, is there anywhere else to go there, or is that pretty much it?

Maha Hussain:
No, I think up until now, I believe this is going to continue to be the backbone until you can come up with some drug that’s going to sort of cure like testis cancer, you know what I’m saying? And I don’t think, right now, we have anything that is a single agent that’s going to do this.

I do think, though, investment, and this is, to me, where the cooperative groups can come in, investment in a multi-targeted sort of strategies, where combination treatments that are rational, biologically logical, to put into that space, specifically in the hormone sensitive space, because if you think about it, and you go through the different disease settings, the basic principle is this.

Moving effective treatment from advanced disease to the earlier stages of the disease gives you a better return on investment, and so I do think we need to get into the adjuvant space. We need to get into the … in prostate metastatic hormone-sensitive space. Bladder is really moving quite rapidly in a positive way, I would say, at the international level, but I think prostate still needs some more investments.

Tom:
Maha, I’ve got a quick question for you. The three cancers that you’ve seen develop over time, prostate, bladder, and kidney cancer, what were the outstanding moments for you in those journeys of those three cancers, when you look back on them?

Maha Hussain:
Well, maybe I’ll begin with kidney. I no longer do kidney cancer, but the fact that we don’t have to use high dose IL-2 is a huge movement.

Tom:
Well Dave McDermott still does, apparently.

Maha Hussain:
So, this is why you, Brian, and et al. need to be in charge, because I always said it was the … We used to call it the interterrible as opposed to interleukin, and it was, without exaggeration, seven sleepless nights that I’m sure you gentlemen have used it. So that would be that. But I would say … Maybe you can ask me one more time, the beginning of the question.

Tom:
The big breakthroughs in prostate, and the big breakthrough in bladder cancer, during your career.

Maha Hussain:
Oh yeah, yeah. So, I think in prostate, the big breakthrough, honestly, is Taxotere, if you ask me my opinion to start with. The concept of androgen receptor targeting is like from the day one, right? The Nobel Prize in the 1940s, that was the basic principle. But the reality of it is this, is … I will tell you that when I look, and sometimes I do, I love history, so when I do presentations, especially to our fellows, to tell them the history, is we think we’re smarter than the people before us. Not really. There were a lot of smart people, it’s just that the investment is research, and the emergence of new ideas and new findings, is really what makes a difference, and so when you look at the history of, let’s say, chemotherapy in prostate cancer, it goes a long time back, right?

Do you remember estramustine and all of that stuff?

Tom:
Yeah.

Brian:
Mm-hmm (affirmative).

Maha Hussain:
And then you Taxotere came in, or docetaxel came in, and that opened up the door to much more investment, because for a long time, it was a disease that nobody wanted to touch, and yeah, we’ve done trials in it, as you know, investigator-initiated trials that went nowhere. So, I would say, to me, that was the biggest space.

The other big area is, I would say, the charted. I think that is a huge thing, and again, while it is Taxotere, it’s all about the concept that you’re moving effective treatment to earlier stages of the disease. So, the reason I don’t mention the BBNs, the this, the that, because that is historically being done, is just that we advanced more effective drugs as opposed to flutamide, and bicalutamide, and stuff like that in that space, and I would say in bladder, to me, the IO, immune therapy has been probably the biggest breakthrough.

Brian:
So, I have a prostate question. What percent of men with advanced metastatic prostate cancer, do you think can be cured with a combination of hormones, SBRT, treatment of the primary, whatever you want to throw at them?

Maha Hussain:
Well, the answer is I don’t know when we talk about cure. What I will tell you that now that we have PSMA, my hope is, if we are using it properly, the opportunity for cure for patients who have, let’s say a PSA relapse, and a PSA PSMA imaging-based finding, where you sort of gang up on the cancer with targeted therapy, systemic therapy, I think the chance for cure is possible.

I will say though, Brian, from the original intermittent trial, SWOG-9346 trial, we looked at 10-year survivorship. Now, mind you, this is on therapy. At that time, and this is, again, we’re talking pretty much the 2000s into the early 2010s, late like 1990s to that era, somewhat about 17% were alive, and I certainly …

Some of them with remission. So, the question comes up is could we cure prostate cancer? I think we can. I just think we have to be careful about how we’re doing it.

Tom:
Maha, couple of …

Maha Hussain:
Which is why I am very much in favor of adjuvant therapy trials for those who are potentially high-risk disease, but also in the hormone sensitive space, where then doing a multi targeted strategy would be the opportunity.

Tom:
Maha, if you were to come into prostate cancer tomorrow, looking back on yourself as a 35-year-old budding oncologist, what would you be looking at from an academic perspective to build the foundations of your career, and how would you go about doing it?

Maha Hussain:
So, I actually think a career is built not by you alone or by me alone, sitting in our rooms and doing nothing. The other part would be not to have expectations that somehow, you’re going to be given the opportunity. You’re going to have to hustle for it, and I will say that I tell that for all my colleagues. Hustle for it, and while …

Basically, show your value, and your value is in commitment in ethics, in … I call it sleep is overrated in the beginning. You need to work, and I do think that’s going to be the most critical part from a career perspective, and open up your mouth when it’s appropriate, and think before you open your mouth, and I say all of these things, partly because this is not about being visible, it’s about being heard and paid attention to, and I think that do your homework is the critical part, and this is exactly what I have my list of …

We do one of these career development type courses, and the part of it is, I think, as fresh blood, I call it, if I am the fresh blood, honestly, that group brings amazing thoughts, because we’re all biased by our own experiences, and you get a new timer, so to speak, coming in, looking at it, and say, “But how come you guys haven’t done this?” And I remember this is what was me 35 years ago. It was like, “How come nobody looked at this thing,” and, “Oh, that’s a good idea.” That would be my mentor’s response. “Okay. Well, why don’t you work on it.”

Tom:
Maha, to expand on that, and this is a … I guess it’s a difficult question, and I don’t know if you can answer it. Do you think the opportunities for new people, for this new blood, are as apparent today as they were 20 or 30 years ago, or do you think there are too many dinosaurs who are running at all, who are orchestrating the work essentially?

Maha Hussain:
You know, I think, if you recall … Well, you may not recall, but in the days when we started, you could count on, literally, on one hand, probably, the medical oncologists, men or women, it doesn’t matter, that were involved academically in prostate cancer, or bladder cancer, or renal cancer, for that matter, and yet there were loads of people who were focused on breast cancer, and yet there’s a lot of talent that grew and is growing through the field, and now that we have more of a crowd in the field of GU oncology, in medical oncology.

I actually think that this is almost reminiscent of breast cancer in the days, and people who are of high equality will make it, irrespective of what’s there, and one thing I would say, Tom, in my days, the people who were more senior …

Or the culture was very much hierarchal, and now I think it’s a bit different, where we’re all kind of equal, and it’s just, yeah, I may be older, but it doesn’t mean I have the upper hand kind of thing. Do you know what I’m saying? So, I don’t know what your experiences are … [crosstalk 00:23:57]

Tom:
That’s bad news for me and Brian.

Brian:
I’d just like to say, I wish Tom would think more before opening his mouth on these questions.

Tom:
Yeah. That’s …

Maha Hussain:
That’s exactly what I was saying.

Tom:
That’s been said to me many times. Many times.

Brian:
I think that’s great advice. Tom, do you want to move to our speed round? We’re about …

Tom:
Yeah, I would like to, but, Maha, before we get there, I’d just like to ask one question. What is the one question that you’d like to answer? If you were in prostate cancer, you’d said you could do one thing now and irrespective of the future, you could get an answer.

It doesn’t matter about money, patients, wherever it was. What’s the one academic question in prostate cancer that you’d like to answer?

Maha Hussain:
I would love, and again, this is not going to be clinical, I think it’s going to be more on the biology end, is mechanisms of resistance. It is puzzling till today, that while there’s a lot of research, and we hear about different resistance mechanisms, and yet you give drugs, you target that pathway, and it works for five minutes, and so this to me is the area that I think is a major issue, and I’ll tell you, we have a spore and there’s a lot of work.

And that’s when one of the things that, when I partnered with the different scientists, is that we need to look at the mechanism of resistance, because really, if one knows what that is, then clearly pre-selecting people ahead of time, and figuring out the pathways, and then drug development in that area is going to be a huge thing.

Tom:
That sounds really good. Brian, let’s move to this rapid round. We’re going through a section now where we’re doing rapid question, so Brian asks a question, then I ask a question. It comes back to this …

Brian:
Some of them are serious, many of Tom’s aren’t, so prepare yourself.

Tom:
Yeah. Comes back to opening your mouth before you’re thinking, which is one of the problems I have in this section.

Brian:
Feel free to take [crosstalk 00:25:43].

Maha Hussain:
And by the way, you guys are free to use that quote.

Brian:
I’m going to be using it a lot, actually.

Maha Hussain:
Yeah, exactly. It’s, yeah. It’s, “Don’t open your mouth before you [crosstalk 00:25:53].”

Brian:
For sure. All right.

Maha Hussain:
Okay.

Brian:
Year and subject matter of your very first publication.

Maha Hussain:
Oh my God. I want to say it’s the eighties sometime. I think.

Brian:
And was it GU related, or was that something else?

Maha Hussain:
Honestly, I don’t remember.

Brian:
Okay. We’ll go to the archives and look.

Tom:
So, my first question is ancient Greece or ancient Egypt?

Maha Hussain:
Age in Greece or age in Egypt?

Tom:
Ancient. As in …

Maha Hussain:
Oh, ancient.

Tom:
Ancient, yeah. Which would you prefer to be in? Ancient Greece or ancient Egypt? You can be a Pharaoh, or a part of the hierarchy of ancient Greece.

Maha Hussain:
I would probably say the Pharaoh. Ancient Egypt.

Tom:
Excellent.

Brian:
Had you not been in medicine and been a physician, what would your career path have been?

Maha Hussain:
Probably art and photography.

Brian:
Oh, awesome.

Maha Hussain:
And I still, by the way, do photography. So, I started painting when I was in middle school …

Brian:
Wow.

Maha Hussain:
… and I sold one painting to … I was in a Catholic school, and I think the nuns made about five dinars, which would’ve been, by today’s standard, probably about one penny, but in the old days, a dinar was $3, so that’s not a bad deal. Yeah.

Brian:
Pretty good.

Maha Hussain:
That was the last painting I painted, and that was the first and the last.

Tom:
Taxotere or abiraterone?

Maha Hussain:
Can I choose both?

Tom:
You can. I don’t see why not. Does that mean you are in favor … I mean, just for my benefit … Oh no. And the audience. Listen. Karim’s excellent recent data on triplet therapy is causing quite a lot of noise. Some people love it, some people aren’t sure. What’s your take on that?

Maha Hussain:
I actually love it. When you look at the data, it looks pretty promising, and very … To me, when you look at progression, objective progression-free survival by imaging, and that’s … If I’m assuming that’s what we’re referring to, to his PEACE trial, I think it looks very real, and I am beginning to actually explore it with patients.

Tom:
So that’s … Just to expand on that. So, what we’re referring to is the recent PEACE-1 trial, which was looking at triplet therapy versus doublet therapy, frontline, prostate cancer, and with a really impressive PFS, but no OS yet, and some people feel we need to wait for OS, and, Maha, you’re saying at the moment, you are exploring it with patients.

Maha Hussain:
Yeah.

Tom:
Brian, over to you.

Brian:
Favorite location you’ve ever given a talk?

Maha Hussain:
Probably two areas. Monte Carlo, and it’s because Monte Carlo, and Greece, and because it’s Greece.

Brian:
We’d like invites to those conferences next time, please.

Maha Hussain:
We will think about it.

Tom:
Maha, I’ve got favorite …

Maha Hussain:
[crosstalk 00:28:38], and I’m sorry. Yeah. If you asked for two, but the third one would be …

Brian:
Sure. I … Yeah.

Maha Hussain:
… Istanbul, I may add that one.

Brian:
Please. I agree.

Maha Hussain:
Turkey. Yeah. Yeah.

Tom:
Well, I’ve actually got … My next question is St. Peters in Rome, or Hagia Sophia, Istanbul. You’ve got to pick a building, Maha. Which one?

Maha Hussain:
Oh my gosh. I love them both.

Tom:
Okay.

Maha Hussain:
Yes.

Tom:
Brian, over to you.

Brian:
One more. Retirement location?

Maha Hussain:
Oh gosh. I would love to be in the Mediterranean.

Tom:
And I’ve got …

Brian:
Sensing a theme here.

Maha Hussain:
Yes. I have to say my favorite destination ever is the Mediterranean, and if Delman, you’ve not been there, I’m sure you have, it is heaven on earth.

Tom:
We did a podcast, actually, just recently from Majorca, would you believe. Like, that’s … So, Maha, I think we’re going to call it. We are delighted to have you. It’s been really exciting, and it’s been very entertaining, for me anyway, to listen to your terrific, incredibly successful career.

Maha Hussain:
I am honored, Tom, to make you entertain me. That’s amazing, and happy … That’s brilliant.

Brian:
Thank you, Maha. Thanks a lot.

Maha Hussain:
Thank you so much.

Brian:
Really appreciate your mentorship throughout the way and all your contributions. Thanks for joining us.

Tom:
Keep well. Bye-bye.

Maha Hussain:
Thank you. Thank you very much, gentlemen.