Report and Lessons Learned From The Consensus Conference For Developing Countries Presentation - Fernando Maluf

September 4, 2019

In this presentation by Fernando Maluf at the 2019 Advanced Prostate Cancer Consensus Conference (APCCC) he summarizes the results of the first Latin American Oncology Group (LACOG) consensus conference, a Cooperative Group Consensus that takes place in Brazil, a consensus conference for developing countries. This unique conference provided guidelines for prostate cancer, specifically for areas of limited resources, comprising 70-75% of the world’s population,


Fernando Maluf, MD, Associate Director – Oncology Center - Beneficência Portuguesa, São Paulo Member of Steering Committee – Oncology Center – Albert Einstein Hospital, São Paulo

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Fernando Maluf: Thank you very much. Thanks to the organizing committee especially to our editors for the kind invitation, and to talk for the first time for the results of the First Global Prostate Cancer Consensus Conference for Developing Countries. I have no conflict of interest for this talk. So this consensus was built to provide the guidelines for the most frequent cancer in men, specifically for areas of resource limitations which comprehends around three-quarters of the world. The methodology applied in the global consensus for developing countries was similar to one that used in the APCCC. The voting members include leader opinions with various specialties, neurologists, medical oncologists, radiation oncologists, radiologists and pathologists from countries from Latin America, Africa, Middle East, Asia, and Eastern Europe. Physicians were generally aware of the costs of diagnostics, follow-up, and treatment tools. And for all the following questions that refer to an area of limited resources, the recommendations should take into account the cost-effectiveness as well as the possible therapies with easier in broader access.

We separate the consensus in different disease states: screening, diagnostic, localized disease, low risk, intermediate risk, advanced disease, so high-risk disease, metastatic disease, castration sensitive in resistant, SOS biochemical recurrence, sensitive, or in-zero CRPC. I'm going to select some of the questions because this consensus involved 350 questions. So I will select some of them that I think is going to be more important and relevant as to give some light.

So we start with the localized low risk and very low risk prostate cancer. So one of the questions is what's the treatment recommendation for an otherwise healthy patient diagnosed with low risk prostate cancer in an area of limited resources? Although there was no other consensus, most of the panelists voted for active surveillance. Another question, in institutions where there is no conform or external beam radiation therapy or IMRT nor robotic laparoscopic surgery nor focal therapy or brachytherapy, what's the recommendation for a man with a higher life expectancy who progressed on active surveillance or who declined active surveillance? In radical prostatectomy was pure consensus with 100% of voters. The panelists did not feel comfortable to recommend cobalt radiation therapy for low risk patient and this was a consensus. 80% of the panelists did not or would not recommend cobalt radiation therapy technique when it's the only technique available.

For localized intermediate risk prostate cancer. The treatment for men with higher life expectancy in a Gleason three plus four in PSA less than 20 and disease confined to the prostate in an area of limited resources? The preferred option was radical prostatectomy by 90% of the panel. The same question for Gleason four per three, so patient population with a poor prognosis. Again, radical prostatectomy was preferred. Remember that in the questions, IMRT was not available for this kind of question. Cobalt radiation therapy as with the low risk disease was not felt to be a good option for patients with intermediate risk disease by 83% of the panel.

Now move on to the high risk and locally advanced prostate cancer. In institutions where there is no availability of IMRT technique. The recommendation of the panel for clinical T3 T4 and/or clinical N+ disease was the combination of hormonal therapy and conformal external beam radiation therapy by 79% of the panel.

On the other hand, for patients where it has been treated in that service, there was no IMRT or conformal radiation therapy and have Gleason eight to 10 PSA more than 20, but disease confined to the prostate. Then radical prostatectomy was a preferred choice by 82% of the panelists. The panelists feel comfortable to recommend conformal conventional radiation therapy for the majority of patients, and as with the low risk and intermediate risk disease for the high risk disease, cobalt radiation therapy, once the only therapy available, was not felt to be really adequate, maybe because of side effects in the optimal dose to be delivered by 83% of the panelists.

In case the option of exclusive hormonal therapy is made for treating high risk prostate cancer, meaning clinical T3 T4 and/or clinical N+ disease, what would be the preference in an area of limited resources? We know that hormonal therapy alone is inferior to hormonal radiation by at least three randomized trials. And the consensus in case of exclusive hormonal therapy is the choice would vote it by 81% of their penalties by ADT with orchiectomy alone and not any kind of medical castration.

So move on to the M1 castration-naive prostate cancer. What hormonal therapy scheme do you recommend for the majority of men with the novel low volume disease in areas of limited resources? And 64% of the panelists voted by orchiectomy alone. The same question, but for a high volume disease, this was almost a consensus. 74.3%, almost 75 voted for ADT plus docetaxel.

If you use castration plus abi in men with castration sensitive naive disease, which abiraterone regimen would recommend for the majority of patients in an area of limited resources, an Abi 250 with fatty food plus pred was the preferred option by 52% of the panelists, which now is quite according with the new NCCN guidelines recommendation for this specific situation.

So move on to the castration-resistant prostate cancer metastatic disease. So we're talking about M1, not M0. The preferred first-line treatment for castration-resistant prostate cancer for men who are asymptomatic or minimally symptomatic who did not receive Doci or Abi in the castration sensitive setting, if full dose of Abi/Enza as well as radium were not available, the panel was the split in two options. Low dose Abi or Docetaxel is exactly the same proportion, 45/45%.

The preferred treatment choice for second-line endocrine manipulation when Abi and Enza were not available if they decide to recommend again our hormonal therapy and not recommended chemotherapy, there was a consensual favoring first-generation AR antagonist.

Now in men with recent prostate cancer, that are symptomatic who did not receive Doci or Abi in the castration sensitive setting. If full doses of Abi and Enza are not available, Docetaxel reached a consensus with 86% of the voters.

Now there is a series of questions regarding what drug you consider to be appropriate as a treatment option in the setting of limited healthcare resources, in men with metastatic CRPC who are progressing on or after docetaxel. So I'm going to point out the drugs that reach a consensus. So Mitoxantrone was a consensus with 85% of the voters. Low dose Abi with 93% of the voters. So drugs that would be reasonable to offer to patients in this setting. DES by 78% of the voters. Ketoconazole and corticosteroids by 85% of the voters. Corticosteroids alone by 88% of the voters. And finally Bicalutamide high dose by 84% of the voters.

These are interesting questions. Remember that in this consensus we come from the idea towards questions that we will pose many, much more difficult. So this is a question for the idea towards in men with metastatic CRPC who had been treated with multiple agents and there is no clinical trial available, what do you recommend a best supportive care at what point? So the majority 45% voted after fifth-line treatment. The same question in areas of limited resources, 45% voted after third-line therapy. So they would stop treatment to line therapy earlier in area of limited resources.

And the last part is the use of osteoclastic target therapy for SRE/SSE prevention for M1 castration-resistant prostate cancer. The bone target therapy preferred by the consensus in area of limited resources was zoledronic acid by 77%. And we asked about the frequency in 75% it reach a consensus every three months instead of every month, which was part of the original publication by Dr. Saad. So the conclusions recommendations in are of limited resources is active surveillance is the preferred option in very low and low risk prostate cancer patients with higher life expectancy. A radical prostatectomy is the preferred option for low risk prostate cancer patients who had progression on active surveillance or for intermediate risk disease particular when robotic IMRT and conformal were not available. This was a consensus.

Cobalt radiation technique was not accepted as a reasonable option for the treatment of localized and local advanced disease. This was also our consensus.

Combination of hormonal therapy and external beam radiation. Even if no IMRTs available is a preferred choice for high risk meaning clinical T3 T4 and/or N+ disease. This was a consensus. An orchiectomy is the preferred hormonal therapy in this scenario.

Radical prostatectomy is a preferred option for high risk prostate cancer with Gleason eight to 10 and/or PSA more than 20 and disease confined to the prostate when there is no availability of IMRT or conformal radiation therapy.

Orchiectomy alone is the preferred option for metastatic castration sensitive low volume disease denoval.

In orchiectomy plus Docetaxel is the preferred option for high volume denoval metastatic castration sensitive prostate cancer.

Orchiectomy associated with docetaxel is a preferred option for metastatic castration-resistant prostate cancer if Abi is not available. Particularly in the symptomatic patients.

In case low dose Abi is available, either Doci or Abi are options to be considered in patients who are asymptomatic or mildly symptomatic. Mitoxantrone DES high dose bicalutamide, ketoconazole, and corticosteroids are options to be considered if no life-prolonging agents are available for metastatic castration-resistant disease.

And zoledronic acid every three months is a preferred bone-target therapy option for metastatic CRPC in patients with bone metastasis to prevent SRE and SSE.

So you're very glad to accomplish a consensus that involved more than a hundred leader opinions for more than 15 countries. In our questionnaire that was built up together with more than 350 questions, and the voting part of eight hours. This was last December. Our hope and our mission and our goal not only as Europeans, but as physicians, is to try to really improve patient care by giving recommendation and maybe some solution alight to doctors that take care of patients like this one.

This is Mr. Silva 72 year old male, who was diagnosed with prostate cancer in Brazil, with high volume denoval disease and cord compression. He lived for only six months. He only had access to castration. He couldn't have radiation therapy to be done and he died with severe neurologic deficits. So our goal and mission is to provide these recommendations to help doctors, which represent three-quarters of the world working in places with severe or moderate resource limitations to help them to find out solutions in order to prolong lives, improve quality of life and outcomes. Certainly better outcomes than Mr. Silva experienced.

I'd like to thank the huge group of more than a hundred colleagues from many parts of the world, including again, Latin America, Middle East, Africa in particular, [inaudible 00:13:22] with me. We are going to do a consensus in ASCO GU for bladder cancer and kidney cancer. So I invite this by mail, all the colleagues from these developing country areas that are facing many, many difficulties to join us. You can email then you can include in this consensus that's going to happen the day before ASCO GU. So thank you very much for the opportunity to share our results with you.