EAU15: High risk PCa: Better curative therapy remains elusive

22 March 2015

Experts examined yesterday controversies, treatment insights and uncertainties in multi-modal approaches in prostate cancer during Plenary Session 2 with some speakers underscoring the lack of convincing data and others reiterating the message that, at best, patients with aggressiveprostate cancer can only be assured of limited survival benefit.

“There are multiple mechanisms of resistance, and the resistance is at the cellular and genetic levels. Some resistance are induced by treatment and some are pre-existing (and rapid),” said Prof. Norman Maitland (GB).

In the session chaired by Profs. Manfred Wirth (DE) and Arnulf Stenzl (DE), among the topics discussed were chemotherapy in hormone sensitive patients, ways to better identify low risk-patients, the roles of surgery and radiotherapy in high-risk patients and Matland’s state-of-the-art lecture on biological resistance of cancer stem cells.

“The combination of standard androgen deprivation therapy (ADT) and six cycles of docetaxel significant improved overall survival compared to standard ADT alone in men with hormone sensitive prostate cancer,” said Christopher Sweeney (USA). He added: “The benefit in patients with a high volume of metastases is clear and justifies the treatment burden, and they need to be chemo-fit.

Discussant Jacques Irani (FR) also conceded he would recommend the ADT-docetaxel combination to those with high-volume, metastatic disease, but noted he would await the publication of confirmative results such as those from the STAMPEDE trial.

In same session the benefits or drawbacks of radiotherapy were examined by Alberto Bossi (FR), Marcus Graefen (DE) and Francesco Montorsi (IT). “I really do not know…we do not have randomized data,” said Bossi replying to the query whether radiotherapy is less toxic than surgery. Graefen, on the other hand, said surgery is the only uni-modal therapy with a realistic chance of cure. “Moreover the results on urinary continence are comparable to low and intermediate-risk disease.”

Montorsi, meanwhile, gave a cautionary message regarding morbidity following mulit-modal treatment. “The risk of short and long-term side effects is not negligible among PCa patients…nonetheless, the harms of a multimodal approach should not preclude its adoption when clinically indicated,” he said.

Maitland gave a well-received state-of-the-art lecture regarding why anti-androgen therapies in prostate cancer fail to offer a better curative treatment. He explained that aside from the mechanisms of resistance to AR (androgen receptor) inhibition, the cancer stem cells, over time and treatment, undergo resistance.

“Anti-androgen treatments shrink tumours but their effects are time-limited,” warned Maitland. He noted that although using aggressive therapy may provide a brief respite with patient’s mortality extended for a limited period, the disease recur at a later stage.

“How can we translate this into clinical practice?” queried Maitland. “We should look into rational combination therapies.”