Combination therapies in prostate cancer

25 November 2016

Systemic treatments and optimizing various forms of therapies in high-risk and metastatic forms of prostate cancer were examined at the first-day plenary session of the 8th European Meeting on Urological Cancers (EMUC16) which opened today in Milan, Italy.

With around 1,300 registered participants, EMUC’s eight edition examines the whole range of issues in onco-urological diseases from the perspectives of medical oncology, urology, radiation oncology, pathology and radiology.

“We aim not only to provide a unique platform for all the specialties but also foster education through a multi-disciplinary approach in collaboration with our colleagues from ESMO, ESTRO and affiliated partners,” said EAU Adjunct Secretary General for Education Hein van Poppel during the opening session where he was joined by Thomas Powles (ESMO), Peter Hoskin (ESTRO), Raymond Owen (ESUR) and Rodolfo Montironi (ESUP).

With the opening session on prostate cancer chaired by Manfred Wirth (DE), Susanne OSanto (NL) and Peter Hoskin (GB), urologist R. Jeffrey Karnes (USA) discussed the optimal use of adjuvant radiation therapy following radical prostatectomy, particularly on current efforts to integrate clinical and genomic features of locally advanced, high-risk disease. He looked into post-operative radiation therapy timing, the findings regarding genomic classifiers in the Decipher study, and various translational studies that examined adjuvant radiation therapy (aRT) versus salvage RT (sRT).

Among the issues that Karnes raised in his presentation are the benefits of sRT for men with low genomic scores (GC), and whether there was a statistically significant decrease in metastases development in men with higher GC who received aRT. He also looked into the issue whether integration of GC can provide additional insights.

“At present we have hypothesis-generating genomic studies (2015-2016) on post-operative RT. Modeling studies indicate cost-effectiveness, and the next step is the application to randomized trials,” said Karnes. He also expected the field to move toward a more personalized approach.

“We hope to see prognostic signatures to better identify ‘aggressive’ disease and risk-stratify such as in the Decipher study,” he said.

Providing the medical oncology perspective, Karim Fizazi (FR) discussed the role of adjuvant systemic approaches following curative treatment, noting that patients with high-risk disease should have a local treatment. He also posed the query: “The worse the prognosis, the higher the benefit from docetaxel?” to which he later gave an affirmative answer.

In his closing remarks, Fizazi said that chemotherapy provides benefit in high-risk localized prostate cancer. “Docetaxel improves recurrence-free survival (RFS) such as shown in the GETUG 12, RTOG 0521 and STAMPEDE trials,” he said. However, he noted that docetaxel’s effect on overall survival is still unknown but with the prospect that new insights can be learned in the next few years.

Meanwhile, urologist Karim Touijer (USA) discussed what can be the best multi-modal approach for node-positive disease as he noted that there is no clear consensus in the management of node-positive disease.

“The choice of therapy is driven by the physician’s preference or institutional standards and these are observation and treatment after biochemical recurrence, adjuvant androgen deprivation therapy (ADT) and a combination of adjuvant ADT plus External Beam Radiation Therapy (EBRT). The benefit of immediate adjuvant treatment over observation is unknown,” he added.

In rounding up his presentation, Touijer stressed that node-positive disease is a heterogeneous group and that maximizing local control with radiation therapy in combination with ADT improves survival.

“Multimodality therapy with radiation and ADT after surgery is of greatest value in patients with the worst pathologic features,” said Touijer. Regarding prospects in the future, he said that molecular imaging could refocus the debate. “Furthermore we need better staging and image-guided therapies,” he said.

Radiation oncologist Gert De Meerleer (BE) presented current developments in salvage radiotherapy for locally recurrent disease, probing into issues such as when and how to deliver the treatment. “Early salvage equals adjuvant radiotherapy,” said De Meerleer, as he noted that adjuvant hormonal treatment improves biochemical relapse free survival (bRFS), distant metastases free survival (DMFS) overall survival, cancer-specific survival (CSS).

Metastatic prostate cancer

In the follow-up session which tackled metastatic prostate cancer, urologist Anders Bjartell (SE) took up oligo and polymetastatic prostate cancer. “Oligo and polymetastatic prostate cancers are more than two distinct entities,” said Bjartell as he underscored that there is a need for more “sensitive and quantitative imaging tools for stratification.”

“Location of metastases may be more important than number of lesions with regards prognosis and treatment,” said Bjartell.

Radiation oncologist Malcolm Mason (GB) gave an update on using chemotherapy in hormone-sensitive prostate cancer and said current guidelines recommend castration combined with chemotherapy to patients whose first presentation is M1 disease and who are fit enough for chemotherapy.

He, however, cautioned that systemic treatment such as docetaxel is “not a trivial treatment” and that chemotherapy-related deaths do occur. “We need greater biological understanding of who benefits,” Mason said.