C.J. Spiller will start against the Colts on Sunday. He’s jumped Fred Jackson, who opened the season as the starter . (US Presswire)

Bills at Colts -- Week 12

Where: Lucas Oil Stadium, Indianapolis (turf, indoors)

When: Sunday, 1 p.m. ET (CBS)

Spread: Colts by 3

Records: Bills (Overall: 4-6, AFC East: 1-3); Colts (Overall: 6-4, AFC South: 2-1)

Past results: Two most recent meetings -- Jan. 3, 2009: Bills 30, Colts 7; Nov. 12, 2006: Colts 17, Bills 16. Series record: Bills hold a 35-30-1 edge.

What matters: Can the Bills get after Andrew Luck? Buffalo’s defense has made some strides in recent weeks, but Luck has lived up to the hype in his first season in the league in leading the Colts to a 6-4 record (2,965 yards, 12 TDs, 12 INTs). DE Kyle Moore (two sacks in the past three weeks) has impressed since stepping into the lineup due to injuries, and Mario Williams (two sacks in the last three weeks, four sacks in the last five weeks) has been better since undergoing left wrist surgery in Week 8. In the secondary, CB Leodis McKelvin has been an upgrade over the injured Aaron Williams (knee) so it’s imperative for the Bills that McKelvin doesn’t revert to his previous inconsistent form.

Who matters: QB Ryan Fitzpatrick, the defensive line, RB C.J. Spiller. Fitzpatrick has performed better over the last month, and the Bills need their quarterback to keep it going in a make-or-break game. Fitzpatrick was solid if not spectacular in Buffalo’s Week 11 win over Miami (17 of 27, 168 yards) but the offense stalled in the red zone (0 for 4). The Bills will need to be better inside the opposing 20 against Indianapolis. Buffalo needs to generate a pass rush with its front four. Defensive coordinator Dave Wannstedt does not like to blitz, so it all comes down to the defensive line. Spiller has jumped Fred Jackson on the depth chart and will get the start at RB, as his previous three starts have come with Jackson injured. Spiller is certainly deserving of the promotion with a remarkable average of 6.4 yards per carry (723 yards, 4 TDs on 109 attempts). The Bills are seventh in the league in rushing (140.8 yards per game) and the Colts are 21st against the run (119.8 yards per game).

Key matchups: Bills CB Stephon Gilmore vs. WR Reggie Wayne, Bills DEs Mario Williams and Kyle Moore vs OLs Anthony Castonzo and Winston Justice. Buffalo’s pass defense has improved over the past several weeks, which coincides with a shift in rookie Gilmore’s responsibilities. Gilmore, Buffalo’s unquestioned top cornerback, moves around to cover the opposnent's top wideout. Before, he stayed primarily on one side. He doesn’t have an easy assignment in Wayne (76 receptions, 1,003 yards, 3 TDs), who remains an elite WR at age 34. Castonzo, a first-round pick of the Colts in 2011, has made plenty of strides this season but he and Justice will have a tough assignment against Williams, Moore and fellow DEs Shawne Merriman and Chris Kelsay.

Injuries of note: DT Kyle Williams (ankle), WR Brad Smith (hamstring), FB Corey McIntyre (knee) and DT Spencer Johnson (ankle) are all dealing with injuries but should be fine to play on Sunday. Kelsay (neck) is hoping to return after missing the last two weeks. DE Mark Anderson and CB Aaron Williams are out.

Inside stuff: Spiller will get the start at RB, but expect Jackson to still be a big part of the team’s plans on offense. Jackson remains a team leader and the Bills could use him in short-yardage situations, an area of concern in Week 11.

Connections: Bills TEs coach Pete Metzelaars spent eight seasons as a coach with the Colts (2002-10).

Stat you should know: The Bills average of 5.2 yards per carry, which would be a team record for a season.

Record watch: With a touchdown pass from Fitzpatrick to WR Stevie Johnson, the duo will become the fourth tandem in team history to connect for at least 22 touchdowns.

Looking ahead: This is a do or die game for the Bills. If they win and get to 5-6, they have two winnable games next up on the schedule -- home games against Jacksonville and St. Louis -- and could push for the final wild card spot in the AFC. .

Prediction: Bills 27, Colts 23

For more updates on the Bills, follow correspondent Mark Ludwiczak on Twitter @CBSBills and @MarkLud12.