New Results Reopen Debate on Testicular Cancer Surveillance

Veronica Hackethal, MD

October 09, 2014

The largest study with longest follow-up to date has added fuel to the ongoing debate over the management of patients with stage I nonseminoma testicular cancer after orchiectomy. Should these patients receive early adjuvant chemotherapy, or should they be followed with surveillance and treated only if there is a relapse?

The study suggests that survival is similar, but that 26% of patients who opt for watchful waiting will need surgery upon relapse. Results were published online on September 29 in the Journal of Clinical Oncology.

"The risk of having surgery for residual tumors after relapse treatment might be higher in surveillance patients compared with those primarily treated with 1 cycle of adjuvant chemotherapy," write Gedske Daugaard, MD, DMSC, professor of oncology at the University of Copenhagen, Denmark, and colleagues.

This changes the balance of risks when weighing the two options, said Ronald de Wit, MD, PhD, professor of medical oncology at Erasmus Medical Center Cancer Institute in Rotterdam, the Netherlands, and author of an accompanying editorial.

This sheds new light on the debate. Watchful waiting has been favored up to now, but "I think this study may indeed change practice," he told Medscape Medical News.

Increased Risk for Additional Surgery

For a median of 15 years, Dr Daugaard and colleagues followed 1226 patients with stage I nonseminoma testicular cancer who had undergone orchiectomy. Surveillance for relapse included tumor markers, CT scans, and clinical exam. The researchers collected data retrospectively by reviewing patient records and pathology reports.

Patients had a median time to relapse of 5 months, and 80% of relapses occurred in the first year.

At 5 years, the overall relapse rate after orchiectomy alone was 31%.

Disease-specific survival at 5 years was 99.3%, at 10 years was 99.3%, and at 15 years was 99.1%.

"A surveillance policy for patients with stage I NSGCC is a safe approach associated with an excellent cure rate and an overall low treatment burden despite a high relapse rate in a small group of patients," the researchers conclude.

"A small high-risk group with a relapse of 50% has been defined and studies with risk-adapted treatment might be an option for these patients," they add.

The study identified three important risk factors for relapse: the presence of vascular invasion, embryonal carcinoma, and rete testis invasion, Dr Daugaard told Medscape Medical News.

In patients with all three of these risk factors, the 5-year relapse rate was 50%. For patients with none of these risk factors, the 5-year relapse rate was 12%.

However, Dr Daugaard cautioned, these risk factors "need prospective validation."

In the study, 26% of patients required surgery for residual tumor masses. Of the 356 patients treated with bleomycin, etoposide, and cisplatin (BEP), 32% required 3 cycles and 58% needed 4 cycles.

It is these results that might lead to a change in practice. Dr de Wit suggested.

Change in Practice?

In fact, many experts in Europe do not feel that surveillance is the only standard, according to Dr de Wit.

Treatment of early-stage nonseminoma testicular cancer in the United States and many European countries relies on orchiectomy and lymph node removal, he explained. Although this cures many patients, there is significant risk for relapse. With a relapse risk from 40% to 50%, patients have two options: 2 cycles of adjuvant chemotherapy or watchful waiting with treatment upon relapse.

Another Danish study, presented last year at the American Society of Clinical Oncology annual meeting, suggested that surveillance was the way to go. It followed patients for 10 years and found that 80% of them could potentially avoid additional adjuvant therapy after orchiectomy.

However, Dr de Wit explained that the problem is that immediate therapy exposes 50% of patients to unnecessary treatment, whereas surveillance with treatment upon relapse usually requires additional chemotherapy in the long-run — about 3 or 4 cycles.

Now the latest study shows that patient who opt for surveillance are also more likely to require further surgery.

Dr de Wit said he found it "astonishing" that in this study, 26% of patients still needed surgery to remove residual masses after 3 or 4 cycles of BEP.

The "frequent" need for additional surgery "sheds light on the balance between the choice of early definitive treatment and chemotherapy at the time of recurrence," Dr de Wit explained. "We have to take into account the sizeable percentage of relapsing patients...who will need surgery."

"It is no longer 2 cycles in all vs 3 in the 50% of patients who relapse," Dr de Wit said. "It is 3 cycles plus the extra risk and burden of additional surgery, which may be quite devastating given the risk for retrograde ejaculation."

Dr de Wit also mentioned "emerging" data suggesting that 1 cycle of BEP, rather than 2, could be enough to avoid the "morbid sequence of 3 BEP cycles plus retroperitoneal lymph node surgery."

"For three decades at my cancer institute — which is the leading testis cancer center in the Netherlands — we have been favoring watchful waiting," Dr de Wit reported. "In my department, we changed just this weekend from surveillance for all to the additional option of offering 1 cycle of BEP. I think many centers may now follow."

The authors and Dr de Wit have disclosed no relevant financial relationships.

J Clin Oncol. Published online on September 29, 2014. Abstract, Editorial


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