Treatment/Prognosis Flashcards
What are the criteria for local excision alone in anal cancer? What are the LC rates in such carefully selected pts?
Small T1 lesion (<2 cm), well differentiated, –margins, <40% circumferential involvement, no sphincter involvement, compliant pts. For these well-selected pts, there is >90% LC. (Boman BM et al., Cancer 1984)
Can radiotherapy alone be employed for early-stage anal cancer?
Yes. However, it can be employed only for T1N0 lesions. There were excellent LC rates of 100% and CR rates of 96% in 1 series. (Deniaud-Alexandre E et al., IJROBP 2003)
What was the standard surgical procedure for anal cancer before the advent of CRT? What was the disadvantage of this approach?
APR was the standard surgical procedure, but the disadvantage is that it requires permanent colostomy.
Currently, when should Sg alone be considered sufficient for management of anal cancer?
Sg is sufficient with anal margin cancers in which the sphincter can be spared.
Historically, what has been the sphincter preservation approach for the Tx of anal cancers?
Radiotherapy alone was employed in Europe since the early 1900s, whereas surgical resection was standard in the United States. Radiotherapy alone produced similar survival and control rates as Sg but allowed sphincter preservation. These results were better for less advanced tumors. Papillon J and Montbarbon JF (Dis Colon Rectum 1987) reported (in the largest series of 159 pts with the use of EBRT and interstitial brachytherapy [30–42 Gy EBRT → implant 15–20 Gy]) a 5-yr OS of 65% and a sphincter preservation rate of 70%–82% (>4-cm tumor vs. ≤4-cm tumor).
What 2 seminal studies from the 1970s and 1980s in the United States demonstrated that surgical resection may not be needed after CRT, even after a short course of Tx?
The Wayne State experience (Nigro ND et al., Dis Colon Rectum 1974, 1983): preop regimen of 30 Gy/15 fx with continuous infusion 5-FU (1,000 mg/m2 × 4 days) and mitomycin-C (MMC) (single 15 mg/m2 bolus), with APR scheduled 6 wks after the regimen. 31 pts had completion Sg vs. 73 had definitive CRT alone. 71% pts had pCR in the surgical specimen. In the Sg arm, the f/u NED rate was 79%. In the definitive CRT arm, the f/u NED rate was 82%.
Princess Margaret Hospital (Cummings BM et al., IJROBP 1991): prospective nonrandomized studies comparing RT alone, 5-FU + RT, or 5-FU/MMC + RT. OS was 70% in all groups, with LC best in the 5-FU/MMC arm of 93% c/w 60% in the RT-alone arm.
What was the chemo regimen and RT dose delivered in the original anal cancer studies by Nigro ND et al.?
In Nigro ND et al., the regimen was 5-FU (1,000 mg/m2 × 4 days)/MMC (15 mg/m2 bolus) with an RT dose of 30 Gy (2 Gy per fx). (Dis Colon Rectum 1974, 1983)
Anal margin tumors are treated like what other cancer?
Anal margin tumors are treated in the same manner as skin cancer.
What is the current Tx paradigm for anal canal cancer?
Anal cancer Tx paradigm: definitive CRT
What chemo doses are used in anal cancer, and what is the scheduling?
Anal cancer doses/scheduling: 5-FU 1,000 mg/m2/day intravenously on days 1–4 and 29–32; MMC 10 mg/m2 IV bolus on days 1 and 29 or 12 mg/m2 IV bolus on day 1 only
What is the main radiobiologic advantage of MMC?
MMC is a hypoxic cell radiosensitizer.
For which pts is APR currently reserved?
APR is reserved as salvage for pts who recur post CRT or those who have had prior pelvic RT.
Are there data directly comparing Sg with CRT in anal cancer?
No. There is no randomized evidence. However, 1 retrospective analysis from Sweden showed better 5-yr OS in pts who rcvd RT ± chemo, supporting CRT as a better initial Tx option. (Goldman S et al., Int J Colorectal Dis 1989)
What 2 major European randomized studies in anal cancer demonstrated the inferiority of definitive RT compared to combined CRT?
UKCCCR (ACT I) (Lancet 1996): 585 pts, any stage, randomized to RT vs. RT + 5-FU/MMC. RT was 45 Gy to the pelvis → 15–25 Gy with ≥50% response. If there was <50% response, then Sg was performed. Response was measured 6 wks after completion of induction therapy. The CR rate trended better in CRT (39% vs. 30%, p = 0.08), with 3-yr LC of 64% vs. 41% (p < 0.0001). The risk of death from anal cancer was also reduced in the CRT arm (HR 0.71, p = 0.02), but there was a nonsignificant benefit of 3-yr OS of 65% vs. 58% (p = 0.25).
13-yr update (Northover J et al., Br J Cancer 2010): The absolute risk of LRR was reduced by 25% and remained stable after 5 yrs. The risk of death was reduced by 12%, and absolute reduction in the colostomy rates remained at 10%, favoring CRT (all SS).
EORTC (Bartelink H et al., JCO 1997): 577 pts, T3–4 or N+, RT vs. RT + 5-FU/MMC. Boost was given based on the response assessed at 6 wks: 20 Gy to CR and 15 Gy to PR. The CR rate was measured after completion of the entire course of therapy. The CR rate was sup in the CRT arm (80% vs. 54%, p = 0.02), as well as 3-yr LC (69% vs. 55%, p = 0.02), but not 3-yr OS (69% vs. 64%).
What is 1 explanation why the United Kingdom Co-ordinating Committee on Cancer Research (UKCCCR) study had substantially inf rates of CR and LC c/w the EORTC study in anal cancer?
The CR rate was measured 6 wks after induction therapy in the UKCCCR, whereas it was measured 6 wks after completion of all therapy in the EORTC study (which had a longer course of Tx b/c boost was not delivered until after 6 wks of initial therapy).
The definition of LC is different b/t the 2 studies. In the UKCCCR study, the definition was more strict, with failure defined as <50% tumor reduction after just 6 wks of 45 Gy to the pelvis.
