Cancer: CT surveillance linked with secondary testicular cancer
Following orchiectomy, patients with testicular cancer who opt out of lymph node dissection in favor of frequent CT surveillance are significantly more likely to develop second malignancies associated with CT radiation as they grow older, according to the findings of a March 15 study published in Cancer.

After surgical removal of a testicle, patients with stage I nonseminomatous germ cell tumors (NSGCT) typically have three choices—chemotherapy, retroperitoneal lymph node dissection (RPLND) or active surveillance for secondary malignancies. According to National Comprehensive Cancer Network guidelines, active surveillance requires frequent CT scans: every two to three months in the first year after orchiectomy, every three to four months in the second year, every four months for the third year, semiannually for the fourth year and annually thereafter.

The authors sought to assess whether this cumulative five-year dose of more than 200 mSv is associated with an increased likelihood of acquiring a second malignancy, compared with patients who opted with RPLND.

Using the Surveillance, Epidemiology and End Results (SEER) registries, the authors identified 7,301 men who were diagnosed with NSGCT between 1988 and 2006, of whom 2,389 underwent RPLND and 4,912 did not. Eighty-four patients developed a second malignancy.

Among the patients who underwent RPLND, 1.3 percent developed a second malignancy, compared with 1.1 percent of those who did not undergo dissection, a non-significant difference. Across the entire sample, RPLND patients experienced improved overall survival and cancer specific survival.

Although the authors found no significant differences in risk of second malignancy according to treatment type, when including patient age in the analysis, they observed that with increasing age patients who underwent RPLND had significantly lower likelihoods of developing second malignancies.

Specifically, the authors calculated that the expected number of second malignancies within 15 years of orchiectomy would be 233 per 10,000 patients who underwent RPLND versus 306 per 10,000 patients who chose active surveillance with CT.

“In other words, unlike the analysis of the entire cohort (in which the vast majority received chemotherapy), those with T1 or T2 clinical stage I disease who do not undergo RPLND, compared with those who do undergo RPLND, are expected to have 22, 52, and 73 more second malignancies at 5 years, 10 years, and 15 years, respectively, per 10,000 treated,” explained Karim Chamie, MD, MSHS, from the department of urology at the University of California, Los Angeles, and colleagues.

Chamie and co-authors also found that when evaluating all stages, the incidence of second malignancies was two-fold to three-fold greater for patients with clinical stage I disease. “We suspect this may be attributed to the widespread use of chemotherapy in this high-risk population (all stages), regardless of treatment type. This implies that the effect size of chemotherapy on the incidence of secondary malignancies may be significantly greater than irradiation from CT imaging,” the authors stated. They acknowledged that further analysis would be required to verify this claim.

Although the incidence rate ratio for acquiring second malignancies (1.37) was relatively low, the authors argued that RPLND’s “prevention of 73 excess second malignancies per 10,000 individuals is a meaningful number, especially in the face of a mortality rate that may be as high as 50 percent among those who develop a malignancy associated with irradiation from CT imaging.

"Indeed, we contend that the excess incidence of second malignancy in patients with clinical stage I disease (73 patients) and a mortality rate of 50 percent (36 deaths) is significant when the cancer-specific mortality rate for those undergoing RPLND is 0.5% (50 patients)."

The authors discussed several relevant limitations to their study, most notably, in their view, was SEER’s omission of patient compliance with CT recommendations. This is especially relevant given a study of 30 million American patients with NSGCT, which found that more than half of the active surveillance patients did not follow the guidelines. The further absence of chemotherapy information could have initiated a substantial effect on second malignancies that was related to chemotherapy instead of CT.

Still, the authors contended that the finding of increased likelihood of developing second malignancy associated with foregoing RPLND “provides compelling, hypothesis-generating data for future studies. This is of paramount importance, because the intense NCCN surveillance regimen appears to be unnecessary—2 CT scans per year yield a detection rate similar to that of 5 CT scans.”